Abstract:
The present invention inter alia provides a method, and use thereof, of predicting severe CVD complications such as AMI or CVD death by detecting the lipid concentrations or lipid ratios of a biological sample and comparing it to a control and has identified specific lipid markers that are more specific and sensitive in predicting these CVD complications than currently utilized clinical markers. Also provided is an antibodies towards said lipids, and the use thereof for predicting, diagnosing, preventing and/or treating CVD complications. The invention additionally relates to kits comprising lipids and/or an antibody thereto, for use in the prediction and/or diagnosis of CVD complications.

Description:
FIELD OF THE INVENTION 
       [0001]    This invention relates to methods and uses involving lipid levels to predict and prevent severe cardiovascular disease-associated fatal complications. The invention thus provides a means to identify and treat high-risk coronary artery disease patients. The methods include analyzing lipid levels of a biological sample, and comparing it to a control. 
       BACKGROUND OF THE INVENTION 
       [0002]    Worldwide, cardiovascular diseases (CVD) are among the leading causes of mortality and morbidity with ever-increasing prevalence. CVD is used to classify numerous conditions that affect the heart, heart valves, blood, and vasculature of the body. One of these conditions is coronary artery disease (CAD). Early targeted initiation of preventive measures of CVD-related fatal complications, such as acute myocardial infarction (AMI) and death, would be of great benefit and can provide a major opportunity in reducing mortality and morbidity in patients suffering from CVD. To this end, accurate identification of individuals who are at risk of developing CVD complications is essential. However, traditional risk assessment fails to recognize a substantial proportion of patients at high risk while a large proportion of individuals are classified as having intermediate risk, leaving patient management uncertain. Additional strategies to further refine risk assessment of high-risk CVD are therefore highly needed. To this end, the inventors have evaluated the role of novel lipidomic biomarkers as a prognostic tool for fatal cardiovascular events in CVD patients. 
         [0003]    Plasma or serum total cholesterol, LDL-cholesterol or HDL-cholesterol concentrations have been used as gold standard biomarkers for CVD/CAD risk prediction. However, a number of coronary artery disease (CAD) or acute myocardial infarction (AMI) patients have LDL-C levels within the recommended range suggesting the need for additional diagnostic measures of the residual risk. It is evident from earlier large scale population studies that these measurements associate with the CAD risk and CAD endpoints such as AMI or cardiovascular death. Therefore, preventive treatment strategies have so far been addressed to lower LDL-C concentrations (mainly by statin treatment) and more recently also attempts to raise HDL-C have been made (e.g., by CETP-inhibitors). On the other hand, it has also been observed that one half of the AMI patients actually do have normal LDL cholesterol levels and that there is a substantial residual risk in statin treated patients despite a LDL-C lowering. Furthermore, recent publications have demonstrated that plasma levels of apolipoprotein B (apoB), the main surface protein on LDL particles, and LDL-C, the amount of cholesterol in those particles, are correlated and, considered separately, as positive risk factors. Plasma levels of apolipoprotein A 1 , the main surface protein on HDL particles, and HDL-C, the amount of cholesterol in those particles, are also correlated with each other and, considered separately, as negative risk factors. Importantly, for a given usual apoB, lower LDL-C has been observed to associate with a higher risk of AMI supporting the view that, on average, LDL particles with low cholesterol content per particle (small, dense LDL particles) are particularly hazardous. Thus, it seems possible that LDL-C associates directly with the more dangerous molecules carried by LDL-particle and that LDL-C is only an indirect measurement of the risk. Therefore, it is of importance to search for molecules e.g., certain lipid species that are directly related with hazardous (i.e., fatal) cardiovascular events. 
         [0004]    Lipid metabolite imbalance is a probable cause of dyslipidemia and the ensuing atherosclerosis manifested in its gravest form as the vulnerable atherosclerotic plaque. Atherosclerotic plaques are complex molecular formations that contain numerous lipids. However, there are other factors than lipid rich plaques or LDL cholesterol that make lipids an attractive group of molecules for CVD studies. Lipids are tightly regulated which makes Lipidomic data robust and informative on the current state of the studied organism. Also, lipids are one of the culmination points of a biological system, more the true outcome than the predictor. Combining Lipidomic data with appropriate biobanked clinical material presents a good opportunity for biomarker discovery. Moreover, lipidomics can be used as a gauge of efficacy and safety in drug development and evolving theragnostics. Lipidomic biomarkers are prime candidates for true companion diagnostics in the CVD area and present many opportunities for improved translational medicine as well. 
         [0005]    The plaque building blocks and lipoprotein components that are thought to traffic lipids to the site of lesion formation can now be resolved with Lipidomic studies correlating lipid structure and composition to function and thereby disease pathogenesis. While the number of lipid mediators in the human body is overwhelming, their identification and quantification is facilitated by the advances in mass spectrometry and lipid biochemistry, which today enable the simultaneous high throughput identification and quantification of hundreds of molecular lipid species in several lipid classes (Ejsing C S, et al:  Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc Natl Acad Sci USA  2009, 106:2136-2141; Stahlman M, et al:  High - throughput shotgun lipidomics by quadrupole time - of - flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci  2009 Hiukka A, et al:  ApoCIII - enriched LDL in type  2  diabetes displays altered lipid composition, increased susceptibility for sphingomyelinase, and increased binding to biglycan. Diabetes  2009, 58:2018-2026; Linden D, et al:  Liver - directed overexpression of mitochondrial glycerol -3- phosphate acyltransferase results in hepatic steatosis, increased triacylglycerol secretion and reduced fatty acid oxidation. FASEB J 2006, 20:434-443.) collectively referred to as the lipidome. Lipidomic studies identify lipid cellular distribution and describe their biochemical mechanisms, interactions and dynamics. Importantly, lipidomics quantifies the exact chemical composition of lipidomes (Han X, Gross R W:  Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. J Lipid Res  2003, 44:1071-1079). 
         [0006]    Due to both high sensitivity and selectivity of lipidomics, even the smallest sample amounts can be analyzed today. The bulk of the lipid data in the art today presents lipids in a sum composition format, i.e. phosphatidylcholine (PC) 34:1 (Brugger B, et al:  Quantitative analysis of biological membrane lipids at the low picomole level by nano - electrospray ionization tandem mass spectrometry. Proc Natl Acad Sci USA  1997, 94:2339-2344) where the molecular lipid and the attached fatty acid tails remain unidentified. The identification of molecular lipid species, e.g., PC 16:0/18:1 (Ekroos K, et al:  Charting molecular composition of phosphatidylcholines by fatty acid scanning and ion trap MS 3  fragmentation. J Lipid Res  2003, 44:2181-2192) is the main feature of advanced lipidomics, which delivers highly resolved molecular lipid species rather than summed fatty acid information. For example, the information of the type of fatty acids and their positions of attachment to the glycerol backbone making up the particular PC molecule is revealed. There are conventional techniques such as thin-layer chromatography combined with gas chromatography but they not only require considerably larger sample amounts and laborious sample preparation, but they do not deliver the molecular lipid species. Despite multiple mass spectrometry techniques capable of characterizing lipid entities, most of them are still unable to deliver reliable high-quality quantitative data in terms of absolute or close-to absolute concentrations. In the context of the present invention, electrospray ionization mass spectrometry-based lipidomics is the preferred technology and can utilize both shotgun and targeted lipidomics for exhaustive deciphering and precise quantification of molecular lipidomes. The superior quality and specificity of shotgun and targeted lipidomics will meet stringent regulatory standards, such as good laboratory practice guidelines (GLP) when set-up in the proper environment. Using these technologies quantification of up to two thousand molecular lipids is possible even in a high throughput format. 
         [0007]    Lipidomics is a tool for differentiating patients based on their molecular lipid profiles. Personalized medicine and diagnostics enabled by lipidomics will facilitate the mission of the right individual receiving the right drug at the right time and dose. Several works employing analytes consisting of lipids, proteins and hydrophilic molecules among many others have been conducted to meet the needs of personalized medicine. Recently, non-hypothesis-driven metabolomic screenings have been used to identify novel CVD biomarkers. 
         [0008]    For example, WO2004/038381 discloses a method for metabolomically facilitating the diagnosis of a disease state of a subject, or for predicting whether a subject is predisposed to having a disease state wherein the small molecule profile from a subject is obtained and compared to a standard small molecule profile. 
         [0009]    WO2008/148857 discloses a method to assess the risk of cardiovascular disease in a patient (including atherosclerosis) by isolating the HDL fraction and sub-fraction from a blood sample of the patient. The components of the HDL fraction or sub-fraction to be measured were Sphingosine-1-Phosphate (SIP), sphingomyelin (SM) and Apolipoprotein A-I (apoA-1). 
         [0010]    WO2008/11943 further discloses markers for detecting coronary artery disease that can indicate a patient at risk of having or developing coronary artery disease. These include 15 “first-choice” molecules which were: C18:3 Cholesterol ester, C32:1 Phosphatidylcholine, Alanine, Lipid (mainly VLDL), Lysine, Hexadecanoic acid, C36:2 Phosphatidylcholine, Formate, C32:2 Phosphatidylcholine, C18:2 (Linoleic Acid), Cholesterol, C 18:2 Lyso-phosphatidylcholine, C36:3 Phosphatidylcholine, C34:4 Phosphatidylcholine and C34:3 Phosphatidylcholine. 
         [0011]    Furthermore, US2007/0099242 describes a method to determine if a subject is at risk to develop, or is suffering from cardiovascular disease. The method involves determining a change in the amount of a biomarker in the biological sample or HDL sub-fraction thereof, compared to a control sample, wherein the biomarker is at least one of Apolipoprotein C-IV (“ApoC-IV”), Paraoxonase 1 (“PON-1”), Complement Factor 3 (“C3”), Apolipoprotein A-IV (“ApoA-IV”), Apolipoprotein E (“ApoE”), Apolipoprotein LI (“ApoL1”), Complement Factor C4 (“C4”), Complement Factor C4B1 (“C4B1”), Histone H2A, Apolipoprotein C-II (“ApoC-II”), Apolipoprotein M (“ApoM”), Vitronectin, Haptoglobin-related Protein and Clusterin. The document also discloses a method for detecting the presence of one or more atherosclerotic lesions wherein a change in the amount of a biomarker in the biological sample or HDL sub-fraction thereof is detected, compared to a control sample and wherein the biomarker is selected from PON-1, C3, C4, ApoE, ApoM and C4B1. All biomarkers mentioned in this document are protein or lipoprotein biomarkers. 
         [0012]    From previous work it cannot be extrapolated that lipid analysis will yield by default a CVD biomarker predictive to the fatal outcomes associated with CVD/CAD. The present invention identifies biomarkers of high risk CVD by absolute, or close to absolute, quantification of defined molecular lipid species instead of profiling multiple analytes Importantly, while many of the existing biomarker candidates are composite fingerprints of multiple factors, the lipidomics approach herein shows value already at a level of single species or ratios thereof. 
         [0013]    In the present invention herein, lipid biomarker concentrations have been measured and quantified in patients with documented CAD who did not show fatal outcomes during the follow-up period (3 years) and in high-risk CAD patients who died due to cardiovascular events during the follow-up period. This invention thus enables accurate usage of the lipid-based biomarkers to identify high risk CVD/CAD patients. Another layer of accuracy was reached through a careful patient selection since it is important to control for factors which may affect the lipid concentration read-outs. Unlike the previous efforts described above, we used specific targeted platforms on a singular technology set-up to analyze lipid species in particular. 
         [0014]    The technology and the way it was applied in the context of the inventive teaching presented herein is set apart from similar efforts in the field inter alia due to the following criteria. In sample preparation, samples are strictly controlled and treated identically to avoid potential artifacts that could arise from improper handling. In connection with the present invention, samples were carefully thawed slowly on ice and directly thereafter subjected to a custom-made automated lipid extraction which possesses currently the highest precision in liquid handling, therefore minimizing potential errors. Furthermore, sample freeze-thaw cycles were strictly controlled since this can dramatically affect the lipid stabilities. The automated lipid extraction is based on the method by Folch and colleagues (Folch J, et al:  A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem  1957, 226(1):497-509) which uses chloroform and methanol. This method is preferred when a wide range, from polar to non-polar, of lipid classes are to be extracted with optimal recoveries thus preventing the loss of lipid species. Lipid class specific non-endogenous lipids, when applicable, were used as internal standards to gain highest precision in identification (minimizing false positives) and quantification of monitored molecular lipid species. In this way absolute or semi-absolute amounts of endogenous molecular lipids were determined with the highest precision that can be achieved with today&#39;s technologies. The endogenous lipids and respective standards were monitored at the molecular lipid level. In this way, not only false positive identifications were minimized, but molecular lipids could be precisely determined and quantified. Analysis quality was strictly controlled using a novel quality control system. This was mainly controlled by multiple internal standards (IS), external standards (ES), IS/ES ratios, and instrument control samples. By stringently controlling these components, technical and biological outliers were readily identified and rejected from further analysis. To obtain best precision in sensitivity, selectivity and quantification for each molecular lipid different targeted platforms were used. Some lipids are best analyzed using high performance liquid chromatography (HPLC) or ultra high performance liquid chromatography (UHPLC) combined with mass spectrometry based multiple reaction monitoring (MRM) whereas others are best analyzed by direct infusion in combination with mass spectrometry-based precursor ion scanning and neutral loss scanning techniques. 
       SUMMARY OF THE INVENTION 
       [0015]    The present invention provides novel lipidomic markers for predicting and preventing severe CVD/CAD-associated complications, including AMI and death. These markers thus provide a means to identify and treat high-risk coronary artery disease patients. Specifically, it has been found that the lipid molecules, lipid-lipid ratios and lipid-clinical concentration ratios provided herein, when displaying an increased or decreased level—as the case may be—in samples from CAD patients, are useful lipidomic markers for the methods and uses in accordance with the present invention. These sensitive and specific markers were specifically tested to display superior diagnostic and prognostic value compared to the current clinically-used markers predictive for CVD/CAD outcomes. In fact, the currently available biomarkers such as LDL-C or HDL-C have only very limited or no value in predicting the CVD death risk in CAD patients. The present invention therefore represents a significant advantage to other markers which are currently used to diagnose and/or predict CVD and CVD complications, which include LDL-C, total plasma/serum cholesterol and Apolipoprotein B and Al. Thus, the lipidomic markers provided herein allow better diagnosis of or assessment of the risk to develop major CVD complications such as AMI or CVD death. 
         [0016]    In accordance with the present invention, methods are inter alia disclosed herein for determining the risk of a patient to develop CVD complications, determining warning signs of CVD risks, (including death, myocardial infarction (MI), angina pectoris, transischemic attack (TIA) and stroke) in said patient. 
         [0017]    Methods according to the invention typically comprise the steps of: a) providing a biological sample from a CAD subject; b) determining a lipid concentration, lipid-lipid ratio, or lipid-clinical concentration ratio or (a) corresponding profile(s) from said sample (i.e., determining information on a lipidomic marker in accordance with the invention); and c) comparing said determined lipid concentration, lipid-lipid ratio, or lipid-clinical concentration ratio or said corresponding profile(s) to the corresponding lipid concentration, lipid-lipid ratio, or lipid-clinical concentration ratio or the corresponding profile(s) in a control. 
         [0018]    The control may be a sample from (a) CAD patient(s) with no history of major CVD events. It may also be a sample that represents a combination of samples from a CAD patient population with no history of major CVD events. Alternatively, the control may be a set of data concerning a lipidomic marker in accordance with the present invention, e.g., information on the concentration of (a) lipid(s), lipid-lipid ratio(s), or lipid-clinical concentration ratio(s) in accordance with the present invention in a sample when taken from (a) CAD patient(s) with no history of major CVD events, or in a combination of samples taken from a CAD patient population with no history of major CVD events. Said information, and thus the corresponding set of data, may have been previously determined, calculated or extrapolated, or may have yet to be determined, calculated or extrapolated, or may also be taken from the literature. 
         [0019]    As mentioned above, the lipidomic marker to be compared between the subject sample and the control (or control sample) may be one or more of the lipid concentration(s), lipid-lipid ratio(s), or lipid-clinical concentration ratio(s) or combinations thereof, i.e., the corresponding profile(s), as described and claimed herein. In this regard, the control or control sample allows establishment of the lipidomic marker baseline or starting point. 
         [0020]    In connection with all aspects and embodiments of the invention described and claimed herein, the determination of the lipid concentration(s), the lipid-lipid ratio(s) or the lipid-clinical concentration ratio(s) is typically performed using an assay. Collecting information on a lipidomic marker (i.e., the concentration(s) of (a) lipid(s), lipid-lipid ratio(s), or lipid-clinical concentration ratio(s) or combinations thereof, i.e., corresponding profile(s)) from the sample of a patient and, where appropriate, a corresponding control sample, can be performed with various chemical and high-resolution analytical techniques. Suitable analytical techniques include, but are not limited to, mass spectrometry and nuclear resonance spectroscopy. Any high-resolution technique capable of resolving individual lipids or lipid classes and providing structural information of the same can be used to collect the information on the lipidomic marker in question, e.g., lipid profile from the biological sample. Collecting the information on the lipidomic marker with mass spectrometry (MS) is one of the preferred embodiments of the current invention. The MS instrument can be coupled to a direct sample infusion method, such as a robotic nanoflow ion source device, or to a high performance separation method such as high performance liquid chromatography (HPLC) or ultra performance liquid chromatography (UPLC). 
         [0021]    Again in accordance with all aspects and embodiments described and claimed herein, both the sample from the subject and the control sample is preferably a blood sample, more preferably a blood plasma sample, or also preferably a blood serum sample. It may also be a fraction of blood, blood plasma or blood serum, e.g., a lipoprotein fraction. A blood sample can be prepared and plasma or serum, or fractions thereof, can be separated therefrom with techniques well known to the person skilled in the art. Alternatively, both the sample from the subject and the control sample may also be a tissue sample, e.g., artery tissue, such as carotid artery tissue, or artery plaque material, such as carotid artery plaque material. 
         [0022]    The lipidomic markers of the present invention allow for prediction and prevention of fatal CVD complications. This will facilitate earlier intervention, less symptom development and suffering and decreased morbidity/mortality associated with CVD. Thus, the lipidomic markers described and claimed herein allow for individual tailoring of drug intervention for patients being at risk to develop major CVD complications. 
         [0023]    In other words, the present invention discloses diagnostic and/or predictive lipid markers and lipid-lipid or lipid-clinical concentration ratios for use in predicting CVD complications such as AMI or CVD death. The invention uses the measurement of lipid concentrations, lipid-lipid and/or lipid-clinical concentration ratios to determine the risk of said subject to develop CVD complications such as AMI and/or CVD death. The subject may have previously suffered from a cardiovascular disease event such as angina pectoris, myocardial infarction or stroke. The CVD may or may not be a result of atherosclerosis. 
         [0024]    Claim  1  (note claims only have preferred embodiments) Accordingly, in one aspect of the invention, a method is provided for determining whether a subject is at risk to develop one or more CVD complications, such as AMI or CVD death, said method comprising determining in a sample from said subject the concentration(s) of one or more lipid(s), wherein (an) increased or decreased concentration(s) in said sample, when compared to a control sample, is (are) indicative of said subject having an increased risk of developing one or more CVD complications, such as AMI or CVD death, wherein the one or more lipid(s) whose increase(s) in concentration is (are) compared to the control is (are) selected from (Tables 4a and 7a): 
         [0000]    Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/24:1), GlcCer(d18:1/18:0), LacCer(d18:1/18:0), LacCer(d18:1/20:0), LacCer(d18:1/22:0), LacCer(d18:1/24:0), PC O-32:0 (KDdiA-PC), PS O-16:0/18:2-alkenyl, PS O-16:1/18:2-alkyl, PS O-18:0/18:2-alkenyl (PS O-18:1/18:2-alkyl), PS O-18:2/16:0-alkenyl and Total LacCer; and wherein the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Tables 4a and 7a):
 
CE 14:0, CE 16:0, CE 17:1, CE 20:3, Cer(d18:0/22:0), Cer(d18:0/24:0), LPC 18:1, PC 16:0/18:2, PC 16:0/20:3, PC 16:0/20:4, PC 16:0/22:6, PC 18:0/18:1, PC 18:0/20:3, PC 18:0/20:4, PC 18:1/18:2, SM (d18:1/14:0) (d18:1/13:1-OH), SM (d18:1/23:0) (d18:1/22:1-OH), SM (d18:1/24:0) (d18:1/23:1-OH), Total CE, Total LPC and Total PC.
 
         [0025]    In a particular embodiment, a method is provided for determining whether a subject is at risk to develop one or more CVD complications, such as AMI or CVD death, wherein the subject is not undergoing statin treatment and wherein said method comprises determining in a sample from said subject the concentration(s) of one or more lipid(s), wherein (an) increased or decreased concentration(s) in said sample, when compared to a control sample, is (are) indicative of said subject having an increased risk of developing one or more CVD complications, such as AMI or CVD death, and wherein the one or more lipid(s) whose increase in concentration is (are) compared to the control is (are) selected from (Tables 4b and 7b): 
         [0000]    Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:1), Cer(d18:1/26:1), GlcCer(d18:1/18:0), GlcCer(d18:1/20:0), GlcCer(d18:1/24:1), GlcCer(d18:1/26:1), LacCer(d18:1/18:0), LacCer(d18:1/20:0), LacCer(d18:1/22:0), LacCer(d18:1/24:0), LacCer(d18:1/24:1), PC O-32:0 (KDdiA-PC), PS O-16:0/18:2-alkenyl, PS O-16:1/18:2-alkyl, PS O-18:2/16:0-alkenyl, Total Cer, Total DAG and Total LacCer;
 
and wherein the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Tables 4b and 7b):
 
       CE 14:0, CE 17:1, CE 20:3, Cer(d18:0/24:0), LPC 18:1, PC 16:0/20:3, PC 16:0/20:4, PC 18:0/20:4, PC O-40:3, SM (d18:1/14:0) (d18:1/13:1-OH), Total LPC and Total PC. 
       [0026]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid(s) whose increase(s) in concentration is (are) compared to the control is (are) selected from (Table 10): 
         [0000]    Cer(d18:1/20:0), LacCer(d18:1/20:0), Cer(d18:1/24:1), LacCer(d18:1/24:1), PS O-18:2/16:0-alkenyl, PS O-16:1/18:2-alkyl, Total Cer, Total LacCer, GlcCer(d18:1/24:1), LacCer(d18:1/22:0) and Cer(d18:1/18:0). 
         [0027]    In another preferred embodiment, the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Table 10): 
       Total PC, PC 16:0/20:4, Cer(d18:0/24:0), Total LPC, CE 14:0, CE 20:3, CE 17:1, PC 16:0/20:3, LPC 18:1, PC 18:0/20:3, PC 18:0/18:1 and Cer(d18:0/22:0). 
       [0028]    In a particularly preferred embodiment, the one or more lipid(s) whose increase(s) in concentration is (are) compared to the control is (are) selected from (Table 13): 
       Cer(d18:1/20:0), LacCer(d18:1/20:0), Cer(d18:1/24:1), LacCer(d18:1/24:1), LacCer(d18:1/22:0) and Cer(d18:1/18:0). 
       [0029]    In another particularly preferred embodiment, the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Table 13): 
       PC 16:0/20:4 and Cer(d18:0/24:0). 
       [0030]    In an alternative embodiment, the present invention relates to a method for determining whether a subject is at risk to develop one or more complications such as AMI or CVD death, comprising determining in a sample from said subject one or more lipid-lipid ratio(s), wherein (an) increased or decreased lipid-lipid ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject having an increased risk of developing one or more CVD complications, such as AMI or CVD death, wherein the one or more lipid-lipid ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 5a and 8a): 
         [0000]    CE 16:0/CE 18:3, CE 18:2/CE 18:3, CE 19:1/Cer(d18:0/22:0), Cer(d18:1/16:0)/LPC 18:1, Cer(d18:1/16:0)/Total PC, Cer(d18:1/18:0)/LPC 16:0, Cer(d18:1/18:0)/LPC 18:1, Cer(d18:1/18:0)/PC 16:0/18:1, Cer(d18:1/18:0)/PC 16:0/20:3, Cer(d18:1/18:0)/PC 16:0/20:4, Cer(d18:1/18:0)/PC 18:0/20:4, Cer(d18:1/18:0)/Total LPC, Cer(d18:1/18:0)/Total PC, Cer(d18:1/20:0)/PC 16:0/18:1, Cer(d18:1/20:0)/PC 16:0/20:3, Cer(d18:1/20:0)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 18:0/20:4, Cer(d18:1/20:0)/PC 18:1/18:1, Cer(d18:1/20:0)/Total PC, Cer(d18:1/22:0)/LPC 18:2, Cer(d18:1/22:0)/PC 16:0/20:3, Cer(d18:1/22:0)/PC 16:0/20:4, Cer(d18:1/22:0)/Total PC, Cer(d18:1/24:1)/LPC 18:1, Cer(d18:1/24:1)/LPC 18:2, Cer(d18:1/24:1)/PC 16:0/18:1, Cer(d18:1/24:1)/PC 16:0/20:3, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/24:1)/PC 18:0/18:1, Cer(d18:1/24:1)/PC 18:0/20:3, Cer(d18:1/24:1)/PC 18:0/20:4, Cer(d18:1/24:1)/SM (d18:1/24:0) (d18:1/23:1-OH), Cer(d18:1/24:1)/Total CE, Cer(d18:1/24:1)/Total LPC, Cer(d18:1/24:1)/Total PC, Cer(d18:1/26:0)/PC O-40:0, GlcCer(d18:1/20:0)/PC 16:0/20:4, GlcCer(d18:1/20:0)/Total PC, GlcCer(d18:1/26:0)/Total CE, LacCer(d18:1/16:0)/Total LPC, LacCer(d18:1/18:0)/PC 16:0/18:1, LacCer(d18:1/18:0)/PC 16:0/20:3, LacCer(d18:1/18:0)/PC 18:0/18:1, LacCer(d18:1/18:0)/PC 18:0/20:3, LacCer(d18:1/18:0)/PC 18:1/18:1, LacCer(d18:1/18:0)/PC 18:1/18:2, LacCer(d18:1/18:0)/Total LPC, LacCer(d18:1/18:0)/Total PC, LacCer(d18:1/20:0)/PC 16:0/18:1, LacCer(d18:1/20:0)/PC 16:0/20:3, LacCer(d18:1/20:0)/PC 18:0/18:1, LacCer(d18:1/20:0)/PC 18:0/20:3 LacCer(d18:1/20:0)/PC 18:1/18:1, LacCer(d18:1/20:0)/PC 18:1/18:2, LacCer(d18:1/20:0)/PC 18:2/18:2, LacCer(d18:1/20:0)/SM (d18:1/17:1-OH), LacCer(d18:1/20:0)/SM (d18:1/18:0), LacCer(d18:1/20:0)/Total LPC, LacCer(d18:1/20:0)/Total PC, LacCer(d18:1/20:0)/Total SM, LacCer(d18:1/22:0)/PC 16:0/20:3, LacCer(d18:1/22:0)/PC 16:0/20:4, LacCer(d18:1/22:0)/PC 18:0/20:3, LacCer(d18:1/22:0)/SM (d18:1/14:0) (d18:1/13:1-OH), LacCer(d18:1/22:0)/Total LPC, LacCer(d18:1/22:0)/Total PC, LacCer(d18:1/24:0)/PC 16:0/20:3, LacCer(d18:1/24:0)/Total LPC, LacCer(d18:1/24:1)/Total LPC, LacCer(d18:1/24:1)/Total PC, LacCer(d18:1/24:1)/Total PC O, PC 16:0/16:0/PC 16:0/20:4, PC 16:0/16:0/Total PC, PC 16:0/18:2/Total PC, PC O-18:0/18:2-alkyl/PC O-36:5, PC O-32:0 (KDdiA-PC)/PC O-38:5, PS O-16:0/18:2-alkenyl/Total PS O, PS O-16:1/18:2-alkyl/Total PS O, PS O-18:0/18:2-alkenyl (PS O-18:1/18:2-alkyl)/Total PS O, PS O-18:2/16:0-alkenyl/Total PS O, Total Cer/Total PC, Total LacCer/Total PC and Total LacCer/Total PC O;
 
and wherein the one or more lipid-lipid ratio(s) whose decrease(s) is (are) compared to the control is (are) selected from (Tables 5a and 8a):
 
CE 14:0/Cer(d18:1/24:1), CE 16:0/Cer(d18:1/24:1), CE 16:1/CE 19:1, CE 16:1/Cer(d18:1/18:0), CE 16:1/Cer(d18:1/20:0), CE 16:1/Cer(d18:1/24:1), CE 16:1/GlcCer(d18:1/18:0), CE 16:1/GlcCer(d18:1/20:0), CE 16:1/LacCer(d18:1/16:0), CE 16:1/LacCer(d18:1/18:0), CE 16:1/LacCer(d18:1/20:0), CE 16:1/LacCer(d18:1/22:0), CE 16:1/LacCer(d18:1/24:0), CE 16:1/PC 16:0/16:0, CE 16:1/Total LacCer, CE 17:1/Cer(d18:1/24:1), CE 17:1/GlcCer(d18:1/24:1), CE 17:1/LacCer(d18:1/18:0), CE 18:1/Total LacCer, CE 18:3/Cer(d18:1/16:0), CE 18:3/Cer(d18:1/18:0), CE 18:3/Cer(d18:1/20:0), CE 18:3/Cer(d18:1/22:0), CE 18:3/Cer(d18:1/24:0), CE 18:3/Cer(d18:1/24:1), CE 18:3/GlcCer(d18:1/18:0), CE 18:3/GlcCer(d18:1/20:0), CE 18:3/LacCer(d18:1/18:0), CE 18:3/LacCer(d18:1/20:0), CE 18:3/LacCer(d18:1/22:0), CE 18:3/LacCer(d18:1/24:0), CE 18:3/PC 16:0/16:0, CE 18:3/PC O-34:1, CE 18:3/PS O-16:0/18:1-alkenyl (PS O-16:1/18:1-alkyl), CE 18:3/PS O-16:0/18:2-alkenyl, CE 18:3/PS O-16:1/18:2-alkyl, CE 18:3/Total CE, CE 18:3/Total Cer, CE 18:3/Total LacCer, CE 20:3/Cer(d18:1/24:1), CE 20:3/LacCer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/LacCer(d18:1/24:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/22:0)/Total CE, Cer(d18:0/24:0)/Cer(d18:1/16:0), Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/20:0), Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/GlcCer(d18:1/20:0), Cer(d18:0/24:0)/LacCer(d18:1/24:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/24:0)/SM (d18:1/17:0) (d18:1/16:1-OH), Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Total Cer, Cer(d18:0/24:1)/Total CE, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), GlcCer(d18:1/26:0)/LacCer(d18:1/22:0), LPC 16:0/LacCer(d18:1/20:0), LPC 16:0/LacCer(d18:1/22:0), LPC 16:0/LacCer(d18:1/24:1), LPC 16:0/Total LacCer, LPC 18:1/LacCer(d18:1/20:0), LPC 18:2/LacCer(d18:1/20:0), LPC 18:2/PS O-16:0/18:2-alkenyl, LPC 18:2/PS O-16:1/18:2-alkyl, PC 16:0/20:3/PS O-16:0/18:2-alkenyl, PC 16:0/20:3/PS O-16:1/18:2-alkyl, PC 18:1/18:2/PS O-16:0/18:2-alkenyl, PC 18:1/18:2/PS O-16:1/18:2-alkyl, SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer and Total LPC/Total LacCer.
 
         [0031]    In an alternative embodiment, the present invention relates to a method for determining whether a subject is at risk to develop one or more complications such as AMI or CVD death, wherein the subject is not undergoing statin treatment and wherein said method comprises determining in a sample from said subject one or more lipid-lipid ratio(s), wherein (an) increased or decreased lipid-lipid ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject having an increased risk of developing one or more CVD complications, such as AMI or CVD death, wherein the one or more lipid-lipid ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 5b and 8b): 
         [0000]    CE 16:0/CE 18:3, CE 18:0/CE 18:3, CE 18:2/CE 18:3, Cer(d18:1/16:0)/LPC 18:1, Cer(d18:1/16:0)/Total PC, Cer(d18:1/18:0)/LPC 18:1, Cer(d18:1/18:0)/PC 16:0/18:1, Cer(d18:1/18:0)/PC 16:0/20:3, Cer(d18:1/18:0)/PC 16:0/20:4, Cer(d18:1/18:0)/PC 18:0/18:1, Cer(d18:1/18:0)/PC 18:0/20:4, Cer(d18:1/18:0)/PC 18:1/18:1, Cer(d18:1/18:0)/SM (d18:1/14:0) (d18:1/13:1-OH), Cer(d18:1/18:0)/SM (d18:1/17:2-OH), Cer(d18:1/18:0)/SM (d18:1/18:1), Cer(d18:1/18:0)/Total CE, Cer(d18:1/18:0)/Total LPC, Cer(d18:1/18:0)/Total PC, Cer(d18:1/20:0)/PC 16:0/18:1, Cer(d18:1/20:0)/PC 16:0/20:3, Cer(d18:1/20:0)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 18:0/18:1, Cer(d18:1/20:0)/PC 18:0/20:4, Cer(d18:1/20:0)/PC 18:1/18:1, Cer(d18:1/20:0)/SM (d18:1/14:0) (d18:1/13:1-OH), Cer(d18:1/20:0)/Total LPC, Cer(d18:1/20:0)/Total PC, Cer(d18:1/20:0)/Total PC O, Cer(d18:1/22:0)/LPC 18:2, Cer(d18:1/22:0)/PC 16:0/20:3, Cer(d18:1/22:0)/PC 16:0/20:4, Cer(d18:1/22:0)/PC 18:0/20:4, Cer(d18:1/22:0)/Total PC, Cer(d18:1/24:1)/LPC 18:1, Cer(d18:1/24:1)/LPC 18:2, Cer(d18:1/24:1)/PC 16:0/18:1, Cer(d18:1/24:1)/PC 16:0/18:2, Cer(d18:1/24:1)/PC 16:0/20:3, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/24:1)/PC 18:0/18:1, Cer(d18:1/24:1)/PC 18:0/18:2, Cer(d18:1/24:1)/PC 18:0/20:3, Cer(d18:1/24:1)/PC 18:0/20:4, Cer(d18:1/24:1)/PC 18:1/18:1, Cer(d18:1/24:1)/PC 18:1/18:2, Cer(d18:1/24:1)/PC O-40:3, Cer(d18:1/24:1)/SM (d18:1/17:1-OH), Cer(d18:1/24:1)/SM (d18:1/18:0), Cer(d18:1/24:1)/SM (d18:1/23:0) (d18:1/22:1-OH), Cer(d18:1/24:1)/SM (d18:1124:0) (d18:1/23:1-OH), Cer(d18:1/24:1)/Total CE, Cer(d18:1/24:1)/Total LPC, Cer(d18:1/24:1)/Total PC, GlcCer(d18:1/26:0)/Total CE, GlcCer(d18:1/26:1)/Total CE, LacCer(d18:1/18:0)/Total PC, LacCer(d18:1/20:0)/PC 16:0/20:3, LacCer(d18:1/20:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 18:0/18:1, LacCer(d18:1/20:0)/PC 18:0/20:3, LacCer(d18:1/20:0)/PC 18:0/20:4, LacCer(d18:1/20:0)/PC 18:1/18:2, LacCer(d18:1/20:0)/SM (d18:1/17:1-OH), LacCer(d18:1/20:0)/SM (d18:1/18:0), LacCer(d18:1/20:0)/Total CE, LacCer(d18:1/20:0)/Total LPC, LacCer(d18:1/20:0)/Total PC, LacCer(d18:1/20:0)/Total SM, LacCer(d18:1/24:0)/Total LPC, PC 16:0/16:0/PC 16:0/20:4, PC 16:0/16:0/Total PC, PC O-32:0 (KDdiA-PC)/Total PC O, PS O-16:0/18:2-alkenyl/Total PC, PS O-16:0/18:2-alkenyl/Total PC O, PS O-16:0/18:2-alkenyl/Total PS O, PS O-16:1/18:2-alkyl/Total PC, PS O-16:1/18:2-alkyl/Total PC O, PS O-16:1/18:2-alkyl/Total PS O, PS O-18:2116:0-alkenyl/Total PC O, PS O-18:2/16:0-alkenyl/Total PS O, SM (d18:1/17:0) (d18:1/16:1-OH)/Total PC O, Total Cer/Total PC, Total DAG/Total LPC, Total DAG/Total PC, Total DAG/Total PC O and Total LacCer/Total PC;
 
and wherein the one or more lipid-lipid ratio(s) whose decrease(s) is (are) compared to the control is (are) selected from (Tables 5b and 8b):
 
CE 14:0/Cer(d18:1/18:0), CE 14:0/Cer(d18:1/24:1), CE 14:0/Total DAG, CE 15:0/Cer(d18:1/20:0), CE 16:0/Cer(d18:1/18:0), CE 16:0/Cer(d18:1/24:1), CE 16:1/CE 19:1, CE 16:1/Cer(d18:1/18:0), CE 16:1/Cer(d18:1/20:0), CE 16:1/Cer(d18:1/24:1), CE 16:1/GlcCer(d18:1/24:1), CE 16:1/LacCer(d18:1/18:0), CE 16:1/LacCer(d18:1/24:0), CE 16:1/Total LacCer, CE 17:1/Cer(d18:1/18:0), CE 17:1/Cer(d18:1/24:1), CE 18:2/Cer(d18:1/20:0), CE 18:2/Cer(d18:1/24:1), CE 18:3/Cer(d18:1/16:0), CE 18:3/Cer(d18:1/18:0), CE 18:3/Cer(d18:1/20:0), CE 18:3/Cer(d18:1/22:0), CE 18:3/Cer(d18:1/24:0), CE 18:3/Cer(d18:1/24:1), CE 18:3/GlcCer(d18:1/20:0), CE 18:3/LacCer(d18:1/20:0), CE 18:3/LacCer(d18:1/22:0), CE 18:3/LacCer(d18:1/24:0), CE 18:3/PC 16:0/16:0, CE 18:3/PC O-34:1, CE 18:3/PS O-16:0/18:2-alkenyl, CE 18:3/PS O-16:1/18:2-alkyl, CE 18:3/Total CE, CE 18:3/Total Cer, CE 18:3/Total DAG, CE 18:3/Total LacCer, CE 20:3/Cer(d18:1/24:1), CE 20:3/LacCer(d18:1/20:0), CE 20:4/Cer(d18:1/18:0), CE 20:4/Cer(d18:1/24:1), CE 20:4/GlcCer(d18:1/20:0), CE 20:4/GlcCer(d18:1/24:1), CE 20:4/LacCer(d18:1/20:0), CE 20:5/LacCer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/22:0)/Total CE, Cer(d18:0/22:0)/Total DAG, Cer(d18:0/22:0)/Total GlcCer, Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/20:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Total Cer, DAG 16:0/18:1/Total DAG, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), LPC 16:0/LacCer(d18:1/24:0), LPC 18:1/LacCer(d18:1/20:0), LPC 18:2/LacCer(d18:1/20:0), PC 16:0/20:3/PS O-16:0/18:2-alkenyl, PC 16:0/20:3/PS O-16:1/18:2-alkyl, PC 16:0/20:4/PS O-16:0/18:2-alkenyl, PC 16:0/20:4/PS O-16:1/18:2-alkyl, PC 16:0/20:4/Total DAG, PC 18:0/20:3/PS O-16:0/18:2-alkenyl, PC 18:0/20:3/PS O-16:1/18:2-alkyl, PC 18:0/20:3/PS O-18:2/16:0-alkenyl, PC 18:0/20:4/PS O-16:0/18:2-alkenyl, PC 18:0/20:4/PS O-16:1/18:2-alkyl, PC 18:1/18:2/PS O-16:0/18:2-alkenyl, PC 18:1/18:2/PS O-16:1/18:2-alkyl, PC 18:1/18:2/Total Cer, PC O-40:3/PS O-18:2/16:0-alkenyl, SM (d18:1/23:0) (d18:1/22:1-OH)/Total DAG, SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer, Total CE/Total DAG and Total LPC/Total LacCer.
 
         [0032]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid-lipid ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 11): 
         [0000]    GlcCer(d18:1/26:1)/Total CE, Cer(d18:1/24:1)/Total PC, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 16:0/20:3, Total Cer/Total PC, Total LacCer/Total PC, LacCer(d18:1/20:0)/PC 18:1/18:2, PS O-16:0/18:2-alkenyl/Total PS O, Cer(d18:1/18:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/Total LPC and LacCer(d18:1/20:0)/PC 16:0/20:4; 
         [0033]    In another preferred embodiment, the one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 11): 
         [0000]    Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/Cer(d18:1/24:1), DAG 16:0/18:1/Total DAG, Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/Total Cer, Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/LacCer(d18:1/24:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), Total LPC/Total LacCer and GlcCer(d18:1/26:0)/LacCer(d18:1/22:0). 
         [0034]    In a particularly preferred embodiment, the one or more lipid-lipid ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 13): 
         [0000]    Cer(d18:1/24:1)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 16:0/20:3, PS O-16:0/18:2-alkenyl/Total PS O and Cer(d18:1/18:0)/PC 16:0/20:4;
 
and the one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 13):
 
GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), DAG 16:0/18:1/Total DAG, Cer(d18:0/24:0)/Total Cer, Total LPC/Total LacCer, GlcCer(d18:1/26:0)/LacCer(d18:1/22:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl and Cer(d18:0/24:0)/LacCer(d18:1/24:0);
 
         [0035]    In yet another alternative embodiment the present invention relates to a method for determining whether a subject is at risk to develop one or more CVD complications, such as AMI or CVD death, comprising determining in a sample from said subject one or more lipid-clinical concentration ratio(s), wherein (an) increased or decreased lipid-clinical concentration ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject having an increased risk of developing one or more CVD complications, such as AMI or CVD death, wherein the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Tables 6a and 9a): 
         [0000]    Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein B (mg/dL), Cer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total-c/HDL-c, Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/20:0)/apolipoprotein B (mg/dL), Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/22:0)/apolipoprotein B (mg/dL), Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein B (mg/dL), Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total-c/HDL-c, Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), GlcCer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/18:0)/apolipoprotein B (mg/dL), LacCer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/total-c/HDL-c, LacCer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/20:0)/apoA1/apoB, LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein B (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL-c/HDL-c, LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/total-c/HDL-c, LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/22:0)/apoA1/apoB, LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein B (mg/dL), LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total-c/HDL-c, LacCer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/24:0)/apoA1/apoB, LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/24:1)/apolipoprotein B (mg/dL), LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), PC O-32:0 (KDdiA-PC)/apolipoprotein A-I (mg/dL), PC O-32:0 (KDdiA-PC)/triglycerides (EDTA) (mg/dL), PC O-34:1/triglycerides (EDTA) (mg/dL), PS O-16:0/18:1-alkenyl (PS O-16:1/18:1-alkyl)/triglycerides (EDTA) (mg/dL), PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL), PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL), PS O-18:2/16:0-alkenyl/HDL cholesterol (EDTA) (mg/dL), PS O-18:2/16:0-alkenyl/triglycerides (EDTA) (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total Cer/total cholesterol (EDTA) (mg/dL), Total Cer/triglycerides (EDTA) (mg/dL), Total GlcCer/apolipoprotein B (mg/dL), Total GlcCer/total cholesterol (EDTA) (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein B (mg/dL), Total LacCer/total cholesterol (EDTA) (mg/dL) and Total LacCer/triglycerides (EDTA) (mg/dL);
 
and wherein the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Tables 6a and 9a):
 
CE 14:0/apolipoprotein B (mg/dL), CE 14:0/LDL cholesterol (EDTA) (mg/dL), CE 14:0/LDL-c/HDL-c, CE 14:0/total cholesterol (EDTA) (mg/dL), CE 14:0/total-c/HDL-c, CE 16:1/apolipoprotein B (mg/dL), CE 16:1/HDL cholesterol (EDTA) (mg/dL), CE 16:1/LDL cholesterol (EDTA) (mg/dL), CE 16:1/total cholesterol (EDTA) (mg/dL), CE 17:1/LDL-c/HDL-c, CE 18:3/apoA1/apoB, CE 18:3/apolipoprotein A-I (mg/dL), CE 18:3/apolipoprotein B (mg/dL), CE 18:3/HDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL-c/HDL-c, CE 18:3/total cholesterol (EDTA) (mg/dL), CE 18:3/total-c/HDL-c, CE 20:3/apolipoprotein B (mg/dL), CE 20:3/LDL-c/HDL-c, CE 20:3/total-c/HDL-c, CE 20:5/apolipoprotein B (mg/dL), CE 20:5/HDL cholesterol (EDTA) (mg/dL), CE 20:5/LDL cholesterol (EDTA) (mg/dL), Cer(d18:0/22:0)/apolipoprotein B (mg/dL), Cer(d18:0/22:0)/LDL-c/HDL-c, Cer(d18:0/22:0)/total-c/HDL-c, Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/LDL-c/HDL-c, Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/total-c/HDL-c, LPC 18:2/apoA1/apoB, LPC 18:2/apolipoprotein B (mg/dL), LPC 18:2/HDL cholesterol (EDTA) (mg/dL), LPC 18:2/LDL cholesterol (EDTA) (mg/dL), LPC 18:2/LDL-c/HDL-c, LPC 18:2/total cholesterol (EDTA) (mg/dL), PC 16:0/20:3/apolipoprotein B (mg/dL), PC 16:0/20:3/HDL cholesterol (EDTA) (mg/dL), PC 16:0/20:3/LDL-c/HDL-c, PC 16:0/20:3/total-c/HDL-c, PC 16:0/20:4/apolipoprotein A-I (mg/dL), PC 16:0/20:4/apolipoprotein B (mg/dL), PC 16:0/20:4/LDL cholesterol (EDTA) (mg/dL), PC 16:0/20:4/LDL-c/HDL-c, PC 16:0120:4/total cholesterol (EDTA) (mg/dL), PC 16:0/20:4/total-c/HDL-c, PC 18:0/18:1/LDL-c/HDL-c, PC 18:0/20:3/LDL-c/HDL-c, PC 18:0/20:3/total-c/HDL-c, PC 18:0/20:4/apoA1/apoB, Total LPC/LDL-c/HDL-c, Total LPC/total-c/HDL-c, Total PC/apolipoprotein B (mg/dL), Total PC/LDL-c/HDL-c, Total PC/total cholesterol (EDTA) (mg/dL) and Total PC/total-c/HDL-c.
 
         [0036]    In yet another alternative embodiment the present invention relates to a method for determining whether a subject is at risk to develop one or more CVD complications, such as AMI or CVD death, wherein the subject is not undergoing statin treatment and wherein said method comprises determining in a sample from said subject one or more lipid-clinical concentration ratio(s), wherein (an) increased or decreased lipid-clinical concentration ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject having an increased risk of developing one or more of CVD complications, such as AMI or CVD death, wherein the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Tables 6b and 9b): 
         [0000]    Cer(d18:1/16:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/16:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein B (mg/dL), Cer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total-c/HDL-c, Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/20:0)/apolipoprotein B (mg/dL), Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total-c/HDL-c, Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/22:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/22:0)/apolipoprotein B (mg/dL), Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/24:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:0)/apolipoprotein B (mg/dL), Cer(d18:1/24:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein B (mg/dL), Cer(d18:1/24:1)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/LDL-c/HDL-c, Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total-c/HDL-c, Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), GlcCer(d18:1/20:0)/apolipoprotein B (mg/dL), GlcCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), GlcCer(d18:1/24:1)/apolipoprotein B (mg/dL), GlcCer(d18:1/26:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/18:0)/apolipoprotein B (mg/dL), LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/apoA1/apoB, LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein B (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL-c/HDL-c, LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/total-c/HDL-c, LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/22:0)/apoA1/apoB, LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein B (mg/dL), LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/24:1)/apolipoprotein B (mg/dL), LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), PC O-34:1/apolipoprotein B (mg/dL), PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL), PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total Cer/apolipoprotein B (mg/dL), Total Cer/LDL cholesterol (EDTA) (mg/dL), Total Cer/total cholesterol (EDTA) (mg/dL), Total DAG/apolipoprotein A-I (mg/dL), Total DAG/triglycerides (EDTA) (mg/dL), Total GlcCer/apolipoprotein B (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein B (mg/dL) and Total LacCer/total cholesterol (EDTA) (mg/dL).
 
and wherein the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Tables 6b and 9b):
 
CE 14:0/apoA1/apoB, CE 14:0/apolipoprotein B (mg/dL), CE 14:0/LDL-c/HDL-c, CE 14:0/total-c/HDL-c, CE 16:1/apoA1/apoB, CE 18:3/apoA1/apoB, CE 18:3/apolipoprotein A-I (mg/dL), CE 18:3/apolipoprotein B (mg/dL), CE 18:3/HDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL-c/HDL-c, CE 18:3/total cholesterol (EDTA) (mg/dL), CE 18:3/total-c/HDL-c, CE 20:5/triglycerides (EDTA) (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/total-c/HDL-c, PC 18:0/20:4/apoA1/apoB, PC O-38:6/apolipoprotein A-I (mg/dL), Total LPC/apoA1/apoB and Total PC/apolipoprotein A-I (mg/dL).
 
         [0037]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 12): 
         [0000]    Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apo lipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein A-1 (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) and Cer(d18:1/24:1)/apolipoprotein B (mg/dL). 
         [0038]    In another preferred embodiment, the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 12): Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), PC 16:0/20:4/apolipoprotein B (mg/dL) and Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL). 
         [0039]    In a particularly preferred embodiment, the lipid-clinical concentration ratio whose increase is compared to the control is (are) selected from (Table 13): 
         [0000]    Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein 
         [0040]    A-I (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) and Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL). 
         [0041]    For the purposes of the invention, and particularly for lipid-clinical concentration ratios, an Apolipoprotein A-I measurement may alternatively be an Apolipoprotein A-II measurement. 
         [0042]    claim  2  (note claims only have preferred embodiments) In another aspect the present invention relates to a method for evaluating the effectiveness of a treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, comprising determining in a sample from said subject the concentration(s) of one or more lipid(s), wherein (an) increased or decreased concentration(s) in said sample, when compared to a control sample, is (are) indicative of effectiveness of said treatment, wherein the one or more lipid(s) whose increase(s) in concentration is (are) compared to the control is (are) selected from (Table 4a and 7a): 
         [0000]    Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/24:1), GlcCer(d18:1/18:0), LacCer(d18:1/18:0), LacCer(d18:1/20:0), LacCer(d18:1/22:0), LacCer(d18:1/24:0), PC O-32:0 (KDdiA-PC), PS O-16:0/18:2-alkenyl, PS O-16:1/18:2-alkyl, PS O-18:0/18:2-alkenyl (PS O-18:1/18:2-alkyl), PS O-18:2/16:0-alkenyl and Total LacCer;
 
and wherein the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Table 4a and 7a):
 
CE 14:0, CE 16:0, CE 17:1, CE 20:3, Cer(d18:0/22:0), Cer(d18:0/24:0), LPC 18:1, PC 16:0/18:2, PC 16:0/20:3, PC 16:0/20:4, PC 16:0/22:6, PC 18:0/18:1, PC 18:0/20:3, PC 18:0/20:4, PC 18:1/18:2, SM (d18:1/14:0) (d18:1/13:1-OH), SM (d18:1/23:0) (d18:1/22:1-OH), SM (d18:1/24:0) (d18:1/23:1-OH), Total CE, Total LPC and Total PC.
 
         [0043]    In a particular embodiment, the present invention relates to a method for evaluating the effectiveness of a treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, wherein the subject is not undergoing statin treatment and wherein said method comprises, determining in a sample from said subject the concentration(s) of one or more lipid(s), wherein (an) increased or decreased concentration(s) in said sample, when compared to a control sample, is (are) indicative of effectiveness of said treatment, wherein the one or more lipid(s) whose increase(s) in concentration is (are) compared to the control is (are) selected from (Table 4b and 7b): 
         [0000]    Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:1), Cer(d18:1/26:1), GlcCer(d18:1/18:0), GlcCer(d18:1/20:0), GlcCer(d18:1/24:1), GlcCer(d18:1/26:1), LacCer(d18:1/18:0), LacCer(d18:1/20:0), LacCer(d18:1/22:0), LacCer(d18:1/24:0), LacCer(d18:1/24:1), PC O-32:0 (KDdiA-PC), PS O-16:0/18:2-alkenyl, PS O-16:1/18:2-alkyl, PS O-18:2/16:0-alkenyl, Total Cer, Total DAG and Total LacCer;
 
and wherein the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Table 4b and 7b):
 
       CE 14:0, CE 17:1, CE 20:3, Cer(d18:0/24:0), LPC 18:1, PC 16:0/20:3, PC 16:0/20:4, PC 18:0/20:4, PC O-40:3, SM (d18:1/14:0) (d18:1/13:1-OH), Total LPC and Total PC. 
       [0044]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid(s) whose increase in concentration is (are) compared to the control is (are) selected from (Table 10): 
         [0000]    Cer(d18:1/20:0), LacCer(d18:1/20:0), Cer(d18:1/24:1), LacCer(d18:1/24:1), PS O-18:2/16:0-alkenyl, PS O-16:1/18:2-alkyl, Total Cer, Total LacCer, GlcCer(d18:1/24:1), LacCer(d18:1/22:0) and Cer(d18:1/18:0). 
         [0045]    In another preferred embodiment, the one or more lipid(s) whose decrease in concentration is (are) compared to the control is (are) selected from (Table 10): Total PC, PC 16:0/20:4, Cer(d18:0/24:0), Total LPC, CE 14:0, CE 20:3, CE 17:1, PC 16:0/20:3, LPC 18:1, PC 18:0/20:3, PC 18:0/18:1 and Cer(d18:0/22:0). 
         [0046]    In a particularly preferred embodiment, the one or more lipid(s) whose increase in concentration is (are) compared to the control is (are) selected from (Table 13): 
       Cer(d18:1/20:0), LacCer(d18:1/20:0), Cer(d18:1/24:1), LacCer(d18:1/24:1), LacCer(d18:1/22:0) and Cer(d18:1/18:0); 
       [0047]    and the one or more lipid(s) whose decrease in concentration is (are) compared to the control is (are) selected from (Table 13): PC 16:0/20:4 and Cer(d18:0/24:0). 
         [0048]    In another alternative embodiment the invention relates to a method for evaluating the effectiveness of a treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, comprising determining in a sample from said subject one or more lipid-lipid ratio(s), wherein (an) increased or decreased lipid-lipid ratio(s) in said sample, when compared to a control sample, is (are) indicative of effectiveness of said treatment, wherein the one or more lipid-lipid ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 5a and 8a): 
         [0000]    CE 16:0/CE 18:3, CE 18:2/CE 18:3, CE 19:1/Cer(d18:0/22:0), Cer(d18:1/16:0)/LPC 18:1, Cer(d18:1/16:0)/Total PC, Cer(d18:1/18:0)/LPC 16:0, Cer(d18:1/18:0)/LPC 18:1, Cer(d18:1/18:0)/PC 16:0/18:1, Cer(d18:1/18:0)/PC 16:0/20:3, Cer(d18:1/18:0)/PC 16:0/20:4, Cer(d18:1/18:0)/PC 18:0/20:4, Cer(d18:1/18:0)/Total LPC, Cer(d18:1/18:0)/Total PC, Cer(d18:1/20:0)/PC 16:0/18:1, Cer(d18:1/20:0)/PC 16:0/20:3, Cer(d18:1/20:0)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 18:0/20:4, Cer(d18:1/20:0)/PC 18:1/18:1, Cer(d18:1/20:0)/Total PC, Cer(d18:1/22:0)/LPC 18:2, Cer(d18:1/22:0)/PC 16:0/20:3, Cer(d18:1/22:0)/PC 16:0/20:4, Cer(d18:1/22:0)/Total PC, Cer(d18:1/24:1)/LPC 18:1, Cer(d18:1/24:1)/LPC 18:2, Cer(d18:1/24:1)/PC 16:0/18:1, Cer(d18:1/24:1)/PC 16:0/20:3, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/24:1)/PC 18:0/18:1, Cer(d18:1/24:1)/PC 18:0/20:3, Cer(d18:1/24:1)/PC 18:0/20:4, Cer(d18:1/24:1)/SM (d18:1/24:0) (d18:1/23:1-OH), Cer(d18:1/24:1)/Total CE, Cer(d18:1/24:1)/Total LPC, Cer(d18:1/24:1)/Total PC, Cer(d18:1/26:0)/PC O-40:0, GlcCer(d18:1/20:0)/PC 16:0/20:4, GlcCer(d18:1/20:0)/Total PC, GlcCer(d18:1/26:0)/Total CE, LacCer(d18:1/16:0)/Total LPC, LacCer(d18:1/18:0)/PC 16:0/18:1, LacCer(d18:1/18:0)/PC 16:0/20:3, LacCer(d18:1/18:0)/PC 18:0/18:1, LacCer(d18:1/18:0)/PC 18:0/20:3, LacCer(d18:1/18:0)/PC 18:1/18:1, LacCer(d18:1/18:0)/PC 18:1/18:2, LacCer(d18:1/18:0)/Total LPC, LacCer(d18:1/18:0)/Total PC, LacCer(d18:1/20:0)/PC 16:0/18:1, LacCer(d18:1/20:0)/PC 16:0/20:3, LacCer(d18:1/20:0)/PC 18:0/18:1, LacCer(d18:1/20:0)/PC 18:0/20:3 LacCer(d18:1/20:0)/PC 18:1/18:1, LacCer(d18:1/20:0)/PC 18:1/18:2, LacCer(d18:1/20:0)/PC 18:2/18:2, LacCer(d18:1/20:0)/SM (d18:1/17:1-OH), LacCer(d18:1/20:0)/SM (d18:1/18:0), LacCer(d18:1/20:0)/Total LPC, LacCer(d18:1/20:0)/Total PC, LacCer(d18:1/20:0)/Total SM, LacCer(d18:1/22:0)/PC 16:0/20:3, LacCer(d18:1/22:0)/PC 16:0/20:4, LacCer(d18:1/22:0)/PC 18:0/20:3, LacCer(d18:1/22:0)/SM (d18:1/14:0) (d18:1/13:1-OH), LacCer(d18:1/22:0)/Total LPC, LacCer(d18:1/22:0)/Total PC, LacCer(d18:1/24:0)/PC 16:0/20:3, LacCer(d18:1/24:0)/Total LPC, LacCer(d18:1/24:1)/Total LPC, LacCer(d18:1/24:1)/Total PC, LacCer(d18:1/24:1)/Total PC O, PC 16:0/16:0/PC 16:0/20:4, PC 16:0/16:0/Total PC, PC 16:0/18:2/Total PC, PC O-18:0/18:2-alkyl/PC O-36:5, PC O-32:0 (KDdiA-PC)/PC O-38:5, PS O-16:0/18:2-alkenyl/Total PS O, PS O-16:1/18:2-alkyl/Total PS O, PS O-18:0/18:2-alkenyl (PS O-18:1/18:2-alkyl)/Total PS O, PS O-18:2/16:0-alkenyl/Total PS O, Total Cer/Total PC, Total LacCer/Total PC and Total LacCer/Total PC O;
 
and wherein one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Tables 5a and 8a):
 
CE 14:0/Cer(d18:1/24:1), CE 16:0/Cer(d18:1/24:1), CE 16:1/CE 19:1, CE 16:1/Cer(d18:1/18:0), CE 16:1/Cer(d18:1/20:0), CE 16:1/Cer(d18:1/24:1), CE 16:1/GlcCer(d18:1/18:0), CE 16:1/GlcCer(d18:1/20:0), CE 16:1/LacCer(d18:1/16:0), CE 16:1/LacCer(d18:1/18:0), CE 16:1/LacCer(d18:1/20:0), CE 16:1/LacCer(d18:1/22:0), CE 16:1/LacCer(d18:1124:0), CE 16:1/PC 16:0/16:0, CE 16:1/Total LacCer, CE 17:1/Cer(d18:1/24:1), CE 17:1/GlcCer(d18:1/24:1), CE 17:1/LacCer(d18:1/18:0), CE 18:1/Total LacCer, CE 18:3/Cer(d18:1/16:0), CE 18:3/Cer(d18:1/18:0), CE 18:3/Cer(d18:1/20:0), CE 18:3/Cer(d18:1/22:0), CE 18:3/Cer(d18:1/24:0), CE 18:3/Cer(d18:1/24:1), CE 18:3/GlcCer(d18:1/18:0), CE 18:3/GlcCer(d18:1/20:0), CE 18:3/LacCer(d18:1/18:0), CE 18:3/LacCer(d18:1/20:0), CE 18:3/LacCer(d18:1/22:0), CE 18:3/LacCer(d18:1/24:0), CE 18:3/PC 16:0/16:0, CE 18:3/PC O-34:1, CE 18:3/PS O-16:0/18:1-alkenyl (PS O-16:1/18:1-alkyl), CE 18:3/PS O-16:0/18:2-alkenyl, CE 18:3/PS O-16:1/18:2-alkyl, CE 18:3/Total CE, CE 18:3/Total Cer, CE 18:3/Total LacCer, CE 20:3/Cer(d18:1/24:1), CE 20:3/LacCer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/LacCer(d18:1/24:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/22:0)/Total CE, Cer(d18:0/24:0)/Cer(d18:1/16:0), Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/20:0), Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/GlcCer(d18:1/20:0), Cer(d18:0/24:0)/LacCer(d18:1/24:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/24:0)/SM (d18:1/17:0) (d18:1/16:1-OH), Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Total Cer, Cer(d18:0/24:1)/Total CE, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), GlcCer(d18:1/26:0)/LacCer(d18:1/22:0), LPC 16:0/LacCer(d18:1/20:0), LPC 16:0/LacCer(d18:1/22:0), LPC 16:0/LacCer(d18:1/24:1), LPC 16:0/Total LacCer, LPC 18:1/LacCer(d18:1/20:0), LPC 18:2/LacCer(d18:1/20:0), LPC 18:2/PS O-16:0/18:2-alkenyl, LPC 18:2/PS O-16:1/18:2-alkyl, PC 16:0/20:3/PS O-16:0/18:2-alkenyl, PC 16:0/20:3/PS O-16:1/18:2-alkyl, PC 18:1/18:2/PS O-16:0/18:2-alkenyl, PC 18:1/18:2/PS O-16:1/18:2-alkyl, SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer and Total LPC/Total LacCer.
 
         [0049]    In another alternative embodiment the invention relates to a method for evaluating the effectiveness of a treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, wherein the subject is not undergoing statin treatment and wherein said method comprises comprising determining in a sample from said subject one or more lipid-lipid ratio(s), wherein (an) increased or decreased lipid-lipid ratio(s) in said sample, when compared to a control sample, is (are) indicative of effectiveness of said treatment, wherein the one or more lipid-lipid ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 5b and 8b): 
         [0000]    CE 16:0/CE 18:3, CE 18:0/CE 18:3, CE 18:2/CE 18:3, Cer(d18:1/16:0)/LPC 18:1, Cer(d18:1/16:0)/Total PC, Cer(d18:1/18:0)/LPC 18:1, Cer(d18:1/18:0)/PC 16:0/18:1, Cer(d18:1/18:0)/PC 16:0/20:3, Cer(d18:1/18:0)/PC 16:0/20:4, Cer(d18:1/18:0)/PC 18:0/18:1, Cer(d18:1/18:0)/PC 18:0/20:4, Cer(d18:1/18:0)/PC 18:1/18:1, Cer(d18:1/18:0)/SM (d18:1/14:0) (d18:1/13:1-OH), Cer(d18:1/18:0)/SM (d18:1/17:2-OH), Cer(d18:1/18:0)/SM (d18:1/18:1), Cer(d18:1/18:0)/Total CE, Cer(d18:1/18:0)/Total LPC, Cer(d18:1/18:0)/Total PC, Cer(d18:1/20:0)/PC 16:0/18:1, Cer(d18:1/20:0)/PC 16:0/20:3, Cer(d18:1/20:0)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 18:0/18:1, Cer(d18:1/20:0)/PC 18:0/20:4, Cer(d18:1/20:0)/PC 18:1/18:1, Cer(d18:1/20:0)/SM (d18:1/14:0) (d18:1/13:1-OH), Cer(d18:1/20:0)/Total LPC, Cer(d18:1/20:0)/Total PC, Cer(d18:1/20:0)/Total PC O, Cer(d18:1/22:0)/LPC 18:2, Cer(d18:1/22:0)/PC 16:0/20:3, Cer(d18:1/22:0)/PC 16:0/20:4, Cer(d18:1/22:0)/PC 18:0/20:4, Cer(d18:1/22:0)/Total PC, Cer(d18:1/24:1)/LPC 18:1, Cer(d18:1/24:1)/LPC 18:2, Cer(d18:1/24:1)/PC 16:0/18:1, Cer(d18:1/24:1)/PC 16:0/18:2, Cer(d18:1/24:1)/PC 16:0/20:3, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/24:1)/PC 18:0/18:1, Cer(d18:1/24:1)/PC 18:0/18:2, Cer(d18:1/24:1)/PC 18:0/20:3, Cer(d18:1/24:1)/PC 18:0/20:4, Cer(d18:1/24:1)/PC 18:1/18:1, Cer(d18:1/24:1)/PC 18:1/18:2, Cer(d18:1/24:1)/PC O-40:3, Cer(d18:1/24:1)/SM (d18:1/17:1-OH), Cer(d18:1/24:1)/SM (d18:1/18:0), Cer(d18:1/24:1)/SM (d18:1/23:0) (d18:1/22:1-OH), Cer(d18:1/24:1)/SM (d18:1/24:0) (d18:1/23:1-OH), Cer(d18:1/24:1)/Total CE, Cer(d18:1/24:1)/Total LPC, Cer(d18:1/24:1)/Total PC, GlcCer(d18:1/26:0)/Total CE, GlcCer(d18:1/26:1)/Total CE, LacCer(d18:1/18:0)/Total PC, LacCer(d18:1/20:0)/PC 16:0/20:3, LacCer(d18:1/20:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 18:0/18:1, LacCer(d18:1/20:0)/PC 18:0/20:3, LacCer(d18:1/20:0)/PC 18:0/20:4, LacCer(d18:1/20:0)/PC 18:1/18:2, LacCer(d18:1/20:0)/SM (d18:1/17:1-OH), LacCer(d18:1/20:0)/SM (d18:1/18:0), LacCer(d18:1/20:0)/Total CE, LacCer(d18:1/20:0)/Total LPC, LacCer(d18:1/20:0)/Total PC, LacCer(d18:1/20:0)/Total SM, LacCer(d18:1/24:0)/Total LPC, PC 16:0/16:0/PC 16:0/20:4, PC 16:0/16:0/Total PC, PC O-32:0 (KDdiA-PC)/Total PC O, PS O-16:0/18:2-alkenyl/Total PC, PS O-16:0/18:2-alkenyl/Total PC O, PS O-16:0/18:2-alkenyl/Total PS O, PS O-16:1/18:2-alkyl/Total PC, PS O-16:1/18:2-alkyl/Total PC O, PS O-16:1/18:2-alkyl/Total PS O, PS O-18:2/16:0-alkenyl/Total PC O, PS O-18:2/16:0-alkenyl/Total PS O, SM (d18:1/17:0) (d18:1/16:1-OH)/Total PC O, Total Cer/Total PC, Total DAG/Total LPC, Total DAG/Total PC, Total DAG/Total PC O and Total LacCer/Total PC;
 
and wherein the one or more lipid-lipid ratio(s) whose decrease(s) is (are) compared to the control is (are) selected from (Tables 5b and 8b):
 
CE 14:0/Cer(d18:1/18:0), CE 14:0/Cer(d18:1/24:1), CE 14:0/Total DAG, CE 15:0/Cer(d18:1/20:0), CE 16:0/Cer(d18:1/18:0), CE 16:0/Cer(d18:1/24:1), CE 16:1/CE 19:1, CE 16:1/Cer(d18:1/18:0), CE 16:1/Cer(d18:1/20:0), CE 16:1/Cer(d18:1/24:1), CE 16:1/GlcCer(d18:1/24:1), CE 16:1/LacCer(d18:1/18:0), CE 16:1/LacCer(d18:1/24:0), CE 16:1/Total LacCer, CE 17:1/Cer(d18:1/18:0), CE 17:1/Cer(d18:1/24:1), CE 18:2/Cer(d18:1/20:0), CE 18:2/Cer(d18:1/24:1), CE 18:3/Cer(d18:1/16:0), CE 18:3/Cer(d18:1/18:0), CE 18:3/Cer(d18:1/20:0), CE 18:3/Cer(d18:1/22:0), CE 18:3/Cer(d18:1/24:0), CE 18:3/Cer(d18:1/24:1), CE 18:3/GlcCer(d18:1/20:0), CE 18:3/LacCer(d18:1/20:0), CE 18:3/LacCer(d18:1/22:0), CE 18:3/LacCer(d18:1/24:0), CE 18:3/PC 16:0/16:0, CE 18:3/PC O-34:1, CE 18:3/PS O-16:0/18:2-alkenyl, CE 18:3/PS O-16:1/18:2-alkyl, CE 18:3/Total CE, CE 18:3/Total Cer, CE 18:3/Total DAG, CE 18:3/Total LacCer, CE 20:3/Cer(d18:1/24:1), CE 20:3/LacCer(d18:1/20:0), CE 20:4/Cer(d18:1/18:0), CE 20:4/Cer(d18:1/24:1), CE 20:4/GlcCer(d18:1/20:0), CE 20:4/GlcCer(d18:1/24:1), CE 20:4/LacCer(d18:1/20:0), CE 20:5/LacCer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl,
 
         [0050]    Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/22:0)/Total CE, Cer(d18:0/22:0)/Total DAG, Cer(d18:0/22:0)/Total GlcCer, Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/20:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Total Cer, DAG 16:0/18:1/Total DAG, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), LPC 16:0/LacCer(d18:1/24:0), LPC 18:1/LacCer(d18:1/20:0), LPC 18:2/LacCer(d18:1/20:0), PC 16:0/20:3/PS O-16:0/18:2-alkenyl, PC 16:0/20:3/PS O-16:1/18:2-alkyl, PC 16:0/20:4/PS O-16:0/18:2-alkenyl, PC 16:0/20:4/PS O-16:1/18:2-alkyl, PC 16:0/20:4/Total DAG, PC 18:0/20:3/PS O-16:0/18:2-alkenyl, PC 18:0/20:3/PS O-16:1/18:2-alkyl, PC 18:0/20:3/PS O-18:2/16:0-alkenyl, PC 18:0/20:4/PS O-16:0/18:2-alkenyl, PC 18:0/20:4/PS O-16:1/18:2-alkyl, PC 18:1/18:2/PS O-16:0/18:2-alkenyl, PC 18:1/18:2/PS O-16:1/18:2-alkyl, PC 18:1/18:2/Total Cer, PC O-40:3/PS O-18:2/16:0-alkenyl, SM (d18:1/23:0) (d18:1/22:1-OH)/Total DAG, SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer, Total CE/Total DAG and Total LPC/Total LacCer. 
         [0051]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid-lipid ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 11): 
         [0000]    GlcCer(d18:1/26:1)/Total CE, Cer(d18:1/24:1)/Total PC, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 16:0/20:3, Total Cer/Total PC, Total LacCer/Total PC, LacCer(d18:1/20:0)/PC 18:1/18:2, PS O-16:0/18:2-alkenyl/Total PS O, Cer(d18:1/18:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/Total LPC and LacCer(d18:1/20:0)/PC 16:0/20:4. 
         [0052]    In another preferred embodiment, the one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 11): 
         [0000]    Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/Cer(d18:1/24:1), DAG 16:0/18:1/Total DAG, Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/Total Cer, Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/LacCer(d18:1/24:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), Total LPC/Total LacCer and GlcCer(d18:1/26:0)/LacCer(d18:1/22:0). 
         [0053]    In a particularly preferred embodiment, the one or more lipid-lipid ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 13): 
         [0000]    Cer(d18:1/24:1)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 16:0/20:3, PS O-16:0/18:2-alkenyl/Total PS O and Cer(d18:1/18:0)/PC 16:0/20:4;
 
and the one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 13):
 
       GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), DAG 16:0/18:1/Total DAG, 
       [0054]    Cer(d18:0/24:0)/Total Cer, Total LPC/Total LacCer, GlcCer(d18:1/26:0)/LacCer(d18:1/22:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl and Cer(d18:0/24:0)/LacCer(d18:1/24:0). 
         [0055]    In yet another alternative embodiment the invention relates to a method for evaluating the effectiveness of a treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, comprising determining in a sample from said subject one or more lipid-clinical concentration ratio(s), wherein (an) increased or decreased lipid-clinical concentration ratio(s) in said sample, when compared to a control sample, is (are) indicative of effectiveness of said treatment, wherein the one or more lipid-clinical concentration ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 6a and 9a): 
         [0000]    Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein B (mg/dL), Cer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total-c/HDL-c, Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/20:0)/apolipoprotein B (mg/dL), Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/22:0)/apolipoprotein B (mg/dL), Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein B (mg/dL), Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total-c/HDL-c, Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), GlcCer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/18:0)/apolipoprotein B (mg/dL), LacCer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/total-c/HDL-c, LacCer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/20:0)/apoA1/apoB, LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein B (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL-c/HDL-c, LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/total-c/HDL-c, LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/22:0)/apoA1/apoB, LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein B (mg/dL), LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total-c/HDL-c, LacCer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/24:0)/apoA1/apoB, LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/24:1)/apolipoprotein B (mg/dL), LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), PC O-32:0 (KDdiA-PC)/apolipoprotein A-I (mg/dL), PC O-32:0 (KDdiA-PC)/triglycerides (EDTA) (mg/dL), PC O-34:1/triglycerides (EDTA) (mg/dL), PS O-16:0/18:1-alkenyl (PS O-16:1/18:1-alkyl)/triglycerides (EDTA) (mg/dL), PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL), PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL), PS O-18:2/16:0-alkenyl/HDL cholesterol (EDTA) (mg/dL), PS O-18:2/16:0-alkenyl/triglycerides (EDTA) (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total Cer/total cholesterol (EDTA) (mg/dL), Total Cer/triglycerides (EDTA) (mg/dL), Total GlcCer/apolipoprotein B (mg/dL), Total GlcCer/total cholesterol (EDTA) (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein B (mg/dL), Total LacCer/total cholesterol (EDTA) (mg/dL) and Total LacCer/triglycerides (EDTA) (mg/dL);
 
and wherein the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from Tables 6a and 9a:
 
CE 14:0/apolipoprotein B (mg/dL), CE 14:0/LDL cholesterol (EDTA) (mg/dL), CE 14:0/LDL-c/HDL-c, CE 14:0/total cholesterol (EDTA) (mg/dL), CE 14:0/total-c/HDL-c, CE 16:1/apolipoprotein B (mg/dL), CE 16:1/HDL cholesterol (EDTA) (mg/dL), CE 16:1/LDL cholesterol (EDTA) (mg/dL), CE 16:1/total cholesterol (EDTA) (mg/dL), CE 17:1/LDL-c/HDL-c, CE 18:3/apoA1/apoB, CE 18:3/apolipoprotein A-I (mg/dL), CE 18:3/apolipoprotein B (mg/dL), CE 18:3/HDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL-c/HDL-c, CE 18:3/total cholesterol (EDTA) (mg/dL), CE 18:3/total-c/HDL-c, CE 20:3/apolipoprotein B (mg/dL), CE 20:3/LDL-c/HDL-c, CE 20:3/total-c/HDL-c, CE 20:5/apolipoprotein B (mg/dL), CE 20:5/HDL cholesterol (EDTA) (mg/dL), CE 20:5/LDL cholesterol (EDTA) (mg/dL), Cer(d18:0/22:0)/apolipoprotein B (mg/dL), Cer(d18:0/22:0)/LDL-c/HDL-c, Cer(d18:0/22:0)/total-c/HDL-c, Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/LDL-c/HDL-c, Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/total-c/HDL-c, LPC 18:2/apoA1/apoB, LPC 18:2/apolipoprotein B (mg/dL), LPC 18:2/HDL cholesterol (EDTA) (mg/dL), LPC 18:2/LDL cholesterol (EDTA) (mg/dL), LPC 18:2/LDL-c/HDL-c, LPC 18:2/total cholesterol (EDTA) (mg/dL), PC 16:0/20:3/apolipoprotein B (mg/dL), PC 16:0/20:3/HDL cholesterol (EDTA) (mg/dL), PC 16:0/20:3/LDL-c/HDL-c, PC 16:0/20:3/total-c/HDL-c, PC 16:0/20:4/apolipoprotein A-I (mg/dL), PC 16:0/20:4/apolipoprotein B (mg/dL), PC 16:0/20:4/LDL cholesterol (EDTA) (mg/dL), PC 16:0/20:4/LDL-c/HDL-c, PC 16:0/20:4/total cholesterol (EDTA) (mg/dL), PC 16:0/20:4/total-c/HDL-c, PC 18:0/18:1/LDL-c/HDL-c, PC 18:0/20:3/LDL-c/HDL-c, PC 18:0/20:3/total-c/HDL-c, PC 18:0/20:4/apoA1/apoB, Total LP C/LDL-c/HDL-c, Total LPC/total-c/HDL-c, Total PC/apolipoprotein B (mg/dL), Total PC/LDL-c/HDL-c, Total PC/total cholesterol (EDTA) (mg/dL) and Total PC/total-c/HDL-c.
 
         [0056]    In yet another alternative embodiment the invention relates to a method for evaluating the effectiveness of a treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, wherein the subject is not undergoing statin treatment and wherein said method comprises determining in a sample from said subject one or more lipid-clinical concentration ratio(s), wherein (an) increased or decreased lipid-clinical concentration ratio(s) in said sample, when compared to a control sample, is (are) indicative of effectiveness of said treatment, wherein the one or more lipid-clinical concentration ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 6b and 9b): 
         [0000]    Cer(d18:1/16:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/16:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein B (mg/dL), C er(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total-c/HDL-c, Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/20:0)/apolipoprotein B (mg/dL), Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total-c/HDL-c, Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/22:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/22:0)/apolipoprotein B (mg/dL), Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/24:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:0)/apolipoprotein B (mg/dL), Cer(d18:1/24:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein B (mg/dL), Cer(d18:1/24:1)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/LDL-c/HDL-c, Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total-c/HDL-c, Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), GlcCer(d18:1/20:0)/apolipoprotein B (mg/dL), GlcCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), GlcCer(d18:1/24:1)/apolipoprotein B (mg/dL), GlcCer(d18:1/26:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/18:0)/apolipoprotein (mg/dL), LacCer(d18:1/18:0)/apolipoprotein B (mg/dL), LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/apoA1/apoB, LacCer(d18:1/20:0)/apolipoprotein (mg/dL), LacCer(d18:1/20:0)/apolipoprotein B (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL-c/HDL-c, LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/total-c/HDL-c, LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/22:0)/apoA1/apoB, LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein B (mg/dL), LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/24:1)/apolipoprotein B (mg/dL), LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), PC O-34:1/apolipoprotein B (mg/dL), PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL), PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total Cer/apolipoprotein B (mg/dL), Total Cer/LDL cholesterol (EDTA) (mg/dL), Total Cer/total cholesterol (EDTA) (mg/dL), Total DAG/apolipoprotein A-I (mg/dL), Total DAG/triglycerides (EDTA) (mg/dL), Total GlcCer/apolipoprotein B (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein B (mg/dL) and Total LacCer/total cholesterol (EDTA) (mg/dL).
 
and wherein the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Tables 6b and 9b):
 
CE 14:0/apoA1/apoB, CE 14:0/apolipoprotein B (mg/dL), CE 14:0/LDL-c/HDL-c, CE 14:0/total-c/HDL-c, CE 16:1/apoA1/apoB, CE 18:3/apoA1/apoB, CE 18:3/apolipoprotein A-I (mg/dL), CE 18:3/apolipoprotein B (mg/dL), CE 18:3/HDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL-c/HDL-c, CE 18:3/total cholesterol (EDTA) (mg/dL), CE 18:3/total-c/HDL-c, CE 20:5/triglycerides (EDTA) (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/total-c/HDL-c, PC 18:0/20:4/apoA1/apoB, PC O-38:6/apolipoprotein A-I (mg/dL), Total LPC/apoA1/apoB and Total PC/apolipoprotein A-I (mg/dL).
 
         [0057]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 12): 
         [0000]    Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) and Cer(d18:1/24:1)/apolipoprotein B (mg/dL). 
         [0058]    In another preferred embodiment, the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 12): 
         [0000]    Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), PC 16:0/20:4/apolipoprotein B (mg/dL) and Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL). 
         [0059]    In a particularly preferred embodiment, the lipid-clinical concentration ratio(s) whose increased is (are) compared to the control are selected from (Table 13): 
         [0000]    Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) and Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL). 
         [0060]    For the purposes of the invention, and particularly for lipid-clinical concentration ratios, an Apolipoprotein A-I measurement may alternatively be an Apolipoprotein A-II measurement. 
         [0061]    Claim  3  (note claims only have preferred embodiments) In yet another aspect the invention relates to a method of choosing an appropriate treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, comprising determining in a sample from said subject the concentration of one or more lipid(s), wherein (an) increased or decreased concentration(s) in said sample, when compared to a control sample, is (are) indicative of said subject being in need of treatment or a change in, or supplementation of, an already administered treatment, wherein the one or more lipid(s) whose increase(s) in concentration is (are) compared to the control is (are) selected from (Tables 4a and 7a): 
         [0000]    Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/24:1), GlcCer(d18:1/18:0), LacCer(d18:1/18:0), LacCer(d18:1/20:0), LacCer(d18:1/22:0), LacCer(d18:1/24:0), PC O-32:0 (KDdiA-PC), PS O-16:0/18:2-alkenyl, PS O-16:1/18:2-alkyl, PS O-18:0/18:2-alkenyl (PS O-18:1/18:2-alkyl), PS O-18:2/16:0-alkenyl and Total LacCer;
 
and wherein the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Tables 4a and 7a):
 
CE 14:0, CE 16:0, CE 17:1, CE 20:3, Cer(d18:0/22:0), Cer(d18:0/24:0), LPC 18:1, PC 16:0/18:2, PC 16:0/20:3, PC 16:0/20:4, PC 16:0/22:6, PC 18:0/18:1, PC 18:0/20:3, PC 18:0/20:4, PC 18:1/18:2, SM (d18:1/14:0) (d18:1/13:1-OH), SM (d18:1/23:0) (d18:1/22:1-OH), SM (d18:1/24:0) (d18:1/23:1-OH), Total CE, Total LPC and Total PC.
 
         [0062]    In yet another aspect the invention relates to a method of choosing an appropriate treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, wherein the subject is not undergoing statin treatment and wherein said method comprises determining in a sample from said subject the concentration of one or more lipid(s), wherein (an) increased or decreased concentration(s) in said sample, when compared to a control sample, is (are) indicative of said subject being in need of treatment or a change in, or supplementation of, an already administered treatment, wherein the one or more lipid(s) whose increase(s) in concentration is (are) compared to the control is (are) selected from (Tables 4b and 7b): 
         [0000]    Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:1), Cer(d18:1/26:1), GlcCer(d18:1/18:0), GlcCer(d18:1/20:0), GlcCer(d18:1/24:1), GlcCer(d18:1/26:1), LacCer(d18:1/18:0), LacCer(d18:1/20:0), LacCer(d18:1/22:0), LacCer(d18:1/24:0), LacCer(d18:1/24:1), PC O-32:0 (KDdiA-PC), PS O-16:0/18:2-alkenyl, PS O-16:1/18:2-alkyl, PS O-18:2/16:0-alkenyl, Total Cer, Total DAG and Total LacCer;
 
and wherein the one or more lipid(s) whose decrease(s) in concentration is (are) compared to the control is (are) selected from (Tables 4b and 7b):
 
       CE 14:0, CE 17:1, CE 20:3, Cer(d18:0/24:0), LPC 18:1, PC 16:0/20:3, PC 16:0/20:4, PC 18:0/20:4, PC O-40:3, SM (d18:1/14:0) (d18:1/13:1-OH), Total LPC and Total PC.  
       [0063]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid(s) whose increase in concentration is (are) compared to the control is (are) selected from (Table 10): 
         [0000]    Cer(d18:1/20:0), LacCer(d18:1/20:0), Cer(d18:1/24:1), LacCer(d18:1/24:1), PS O-18:2/16:0-alkenyl, PS O-16:1/18:2-alkyl, Total Cer, Total LacCer, GlcCer(d18:1/24:1), LacCer(d18:1/22:0) and Cer(d18:1/18:0). 
         [0064]    In another preferred embodiment, the one or more lipid(s) whose decrease in concentration is (are) compared to the control is (are) selected from (Table 10): 
       Total PC, PC 16:0/20:4, Cer(d18:0/24:0), Total LPC, CE 14:0, CE 20:3, CE 17:1, PC 16:0/20:3, LPC 18:1, PC 18:0/20:3, PC 18:0/18:1 and Cer(d18:0/22:0). 
       [0065]    In a particularly preferred embodiment, the one or more lipid(s) whose increase in concentration is (are) compared to the control is (are) selected from (Table 13): 
       Cer(d18:1/20:0), LacCer(d18:1/20:0), Cer(d18:1/24:1), LacCer(d18:1/24:1), LacCer(d18:1/22:0) and Cer(d18:1/18:0); 
       [0066]    and the one or more lipid(s) whose decrease in concentration is (are) compared to the control is (are) selected from (Table 13): PC 16:0/20:4 and Cer(d18:0/24:0). 
         [0067]    In an alternative embodiment the invention relates to a method of choosing an appropriate treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, comprising determining in a sample from said subject one or more lipid-lipid ratio(s), wherein (an) increased or decreased lipid-lipid ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject being in need of treatment or a change in, or supplementation of, an already administered treatment, wherein the one or more lipid-lipid ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 5a and 8a): 
         [0000]    CE 16:0/CE 18:3, CE 18:2/CE 18:3, CE 19:1/Cer(d18:0/22:0), Cer(d18:1/16:0)/LPC 18:1, Cer(d18:1/16:0)/Total PC, Cer(d18:1/18:0)/LPC 16:0, Cer(d18:1/18:0)/LPC 18:1, Cer(d18:1/18:0)/PC 16:0/18:1, Cer(d18:1/18:0)/PC 16:0/20:3, Cer(d18:1/18:0)/PC 16:0/20:4, Cer(d18:1/18:0)/PC 18:0/20:4, Cer(d18:1/18:0)/Total LPC, Cer(d18:1/18:0)/Total PC, Cer(d18:1/20:0)/PC 16:0/18:1, Cer(d18:1/20:0)/PC 16:0/20:3, Cer(d18:1/20:0)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 18:0/20:4, Cer(d18:1/20:0)/PC 18:1/18:1, Cer(d18:1/20:0)/Total PC, Cer(d18:1/22:0)/LPC 18:2, Cer(d18:1/22:0)/PC 16:0/20:3, Cer(d18:1/22:0)/PC 16:0/20:4, Cer(d18:1/22:0)/Total PC, Cer(d18:1/24:1)/LPC 18:1, Cer(d18:1/24:1)/LPC 18:2, Cer(d18:1/24:1)/PC 16:0/18:1, Cer(d18:1/24:1)/PC 16:0/20:3, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/24:1)/PC 18:0/18:1, Cer(d18:1/24:1)/PC 18:0/20:3, Cer(d18:1/24:1)/PC 18:0/20:4, Cer(d18:1/24:1)/SM (d18:1/24:0) (d18:1/23:1-OH), Cer(d18:1/24:1)/Total CE, Cer(d18:1/24:1)/Total LPC, Cer(d18:1/24:1)/Total PC, Cer(d18:1/26:0)/PC O-40:0, GlcCer(d18:1/20:0)/PC 16:0/20:4, GlcCer(d18:1/20:0)/Total PC, GlcCer(d18:1/26:0)/Total CE, LacCer(d18:1/16:0)/Total LPC, LacCer(d18:1/18:0)/PC 16:0/18:1, LacCer(d18:1/18:0)/PC 16:0/20:3, LacCer(d18:1/18:0)/PC 18:0/18:1, LacCer(d18:1/18:0)/PC 18:0/20:3, LacCer(d18:1/18:0)/PC 18:1/18:1, LacCer(d18:1/18:0)/PC 18:1/18:2, LacCer(d18:1/18:0)/Total LPC, LacCer(d18:1/18:0)/Total PC, LacCer(d18:1/20:0)/PC 16:0/18:1, LacCer(d18:1/20:0)/PC 16:0/20:3, LacCer(d18:1/20:0)/PC 18:0/18:1, LacCer(d18:1/20:0)/PC 18:0/20:3 LacCer(d18:1/20:0)/PC 18:1/18:1, LacCer(d18:1/20:0)/PC 18:1/18:2, LacCer(d18:1/20:0)/PC 18:2/18:2, LacCer(d18:1/20:0)/SM (d18:1/17:1-OH), LacCer(d18:1/20:0)/SM (d18:1/18:0), LacCer(d18:1/20:0)/Total LPC, LacCer(d18:1/20:0)/Total PC, LacCer(d18:1/20:0)/Total SM, LacCer(d18:1/22:0)/PC 16:0/20:3, LacCer(d18:1/22:0)/PC 16:0/20:4, LacCer(d18:1/22:0)/PC 18:0/20:3, LacCer(d18:1/22:0)/SM (d18:1/14:0) (d18:1113:1-OH), LacCer(d18:1/22:0)/Total LPC, LacCer(d18:1/22:0)/Total PC, LacCer(d18:1/24:0)/PC 16:0/20:3, LacCer(d18:1/24:0)/Total LPC, LacCer(d18:1/24:1)/Total LPC, LacCer(d18:1/24:1)/Total PC, LacCer(d18:1/24:1)/Total PC O, PC 16:0/16:0/PC 16:0/20:4, PC 16:0/16:0/Total PC, PC 16:0/18:2/Total PC, PC O-18:0/18:2-alkyl/PC O-36:5, PC O-32:0 (KDdiA-PC)/PC O-38:5, PS O-16:0/18:2-alkenyl/Total PS O, PS O-16:1/18:2-alkyl/Total PS O, PS O-18:0/18:2-alkenyl (PS O-18:1/18:2-alkyl)/Total PS O, PS O-18:2/16:0-alkenyl/Total PS O, Total Cer/Total PC, Total LacCer/Total PC and Total LacCer/Total PC O;
 
and wherein one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Tables 5a and 8a):
 
CE 14:0/Cer(d18:1/24:1), CE 16:0/Cer(d18:1/24:1), CE 16:1/CE 19:1, CE 16:1/Cer(d18:1/18:0), CE 16:1/Cer(d18:1/20:0), CE 16:1/Cer(d18:1/24:1), CE 16:1/GlcCer(d18:1/18:0), CE 16:1/GlcCer(d18:1/20:0), CE 16:1/LacCer(d18:1/16:0), CE 16:1/LacCer(d18:1/18:0), CE 16:1/LacCer(d18:1/20:0), CE 16:1/LacCer(d18:1/22:0), CE 16:1/LacCer(d18:1/24:0), CE 16:1/PC 16:0/16:0, CE 16:1/Total LacCer, CE 17:1/Cer(d18:1/24:1), CE 17:1/GlcCer(d18:1/24:1), CE 17:1/LacCer(d18:1/18:0), CE 18:1/Total LacCer, CE 18:3/Cer(d18:1/16:0), CE 18:3/Cer(d18:1/18:0), CE 18:3/Cer(d18:1/20:0), CE 18:3/Cer(d18:1/22:0), CE 18:3/Cer(d18:1/24:0), CE 18:3/Cer(d18:1/24:1), CE 18:3/GlcCer(d18:1/18:0), CE 18:3/GlcCer(d18:1/20:0), CE 18:3/LacCer(d18:1/18:0), CE 18:3/LacCer(d18:1/20:0), CE 18:3/LacCer(d18:1/22:0), CE 18:3/LacCer(d18:1/24:0), CE 18:3/PC 16:0/16:0, CE 18:3/PC O-34:1, CE 18:3/PS O-16:0/18:1-alkenyl (PS O-16:1/18:1-alkyl), CE 18:3/PS O-16:0/18:2-alkenyl, CE 18:3/PS O-16:1/18:2-alkyl, CE 18:3/Total CE, CE 18:3/Total Cer, CE 18:3/Total LacCer, CE 20:3/Cer(d18:1/24:1), CE 20:3/LacCer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/LacCer(d18:1/24:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/22:0)/Total CE, Cer(d18:0/24:0)/Cer(d18:1/16:0), Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/20:0), Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/GlcCer(d18:1/20:0), Cer(d18:0/24:0)/LacCer(d18:1/24:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/24:0)/SM (d18:1/17:0) (d18:1/16:1-OH), Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Total Cer, Cer(d18:0/24:1)/Total CE, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), GlcCer(d18:1/26:0)/LacCer(d18:1/22:0), LPC 16:0/LacCer(d18:1/20:0), LPC 16:0/LacCer(d18:1/22:0), LPC 16:0/LacCer(d18:1/24:1), LPC 16:0/Total LacCer, LPC 18:1/LacCer(d18:1/20:0), LPC 18:2/LacCer(d18:1/20:0), LPC 18:2/PS O-16:0/18:2-alkenyl, LPC 18:2/PS O-16:1/18:2-alkyl, PC 16:0/20:3/PS O-16:0/18:2-alkenyl, PC 16:0/20:3/PS O-16:1/18:2-alkyl, PC 18:1/18:2/PS O-16:0/18:2-alkenyl, PC 18:1/18:2/PS O-16:1/18:2-alkyl, SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer and Total LPC/Total LacCer.
 
         [0068]    In an alternative embodiment the invention relates to a method of choosing an appropriate treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, wherein the subject is not undergoing statin treatment and wherein said method comprises determining in a sample from said subject one or more lipid-lipid ratio(s), wherein (an) increased or decreased lipid-lipid ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject being in need of treatment or a change in, or supplementation of, an already administered treatment, wherein the one or more lipid-lipid ratio(s) whose increase(s) is (are) compared to the control is (are) selected from (Tables 5b and 8b): 
         [0000]    CE 16:0/CE 18:3, CE 18:0/CE 18:3, CE 18:2/CE 18:3, Cer(d18:1/16:0)/LPC 18:1, Cer(d18:1/16:0)/Total PC, Cer(d18:1/18:0)/LPC 18:1, Cer(d18:1/18:0)/PC 16:0/18:1, Cer(d18:1/18:0)/PC 16:0/20:3, Cer(d18:1/18:0)/PC 16:0/20:4, Cer(d18:1/18:0)/PC 18:0/18:1, Cer(d18:1/18:0)/PC 18:0/20:4, Cer(d18:1/18:0)/PC 18:1/18:1, Cer(d18:1/18:0)/SM (d18:1/14:0) (d18:1/13:1-OH), Cer(d18:1/18:0)/SM (d18:1/17:2-OH), Cer(d18:1/18:0)/SM (d18:1/18:1), Cer(d18:1/18:0)/Total CE, Cer(d18:1/18:0)/Total LPC, Cer(d18:1/18:0)/Total PC, Cer(d18:1/20:0)/PC 16:0/18:1, Cer(d18:1/20:0)/PC 16:0/20:3, Cer(d18:1/20:0)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 18:0/18:1, Cer(d18:1/20:0)/PC 18:0/20:4, Cer(d18:1/20:0)/PC 18:1/18:1, Cer(d18:1/20:0)/SM (d18:1/14:0) (d18:1/13:1-OH), Cer(d18:1/20:0)/Total LPC, Cer(d18:1/20:0)/Total PC, Cer(d18:1/20:0)/Total PC O, Cer(d18:1/22:0)/LPC 18:2, Cer(d18:1/22:0)/PC 16:0/20:3, Cer(d18:1/22:0)/PC 16:0/20:4, Cer(d18:1/22:0)/PC 18:0/20:4, Cer(d18:1/22:0)/Total PC, Cer(d18:1/24:1)/LPC 18:1, Cer(d18:1/24:1)/LPC 18:2, Cer(d18:1/24:1)/PC 16:0/18:1, Cer(d18:1/24:1)/PC 16:0/18:2, Cer(d18:1/24:1)/PC 16:0/20:3, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/24:1)/PC 18:0/18:1, Cer(d18:1/24:1)/PC 18:0/18:2, Cer(d18:1/24:1)/PC 18:0/20:3, Cer(d18:1/24:1)/PC 18:0/20:4, Cer(d18:1/24:1)/PC 18:1/18:1, Cer(d18:1/24:1)/PC 18:1/18:2, Cer(d18:1/24:1)/PC O-40:3, Cer(d18:1/24:1)/SM (d18:1/17:1-OH), Cer(d18:1/24:1)/SM (d18:1/18:0), Cer(d18:1/24:1)/SM (d18:1/23:0) (d18:1/22:1-OH), Cer(d18:1/24:1)/SM (d18:1124:0) (d18:1/23:1-OH), Cer(d18:1/24:1)/Total CE, Cer(d18:1/24:1)/Total LPC, Cer(d18:1/24:1)/Total PC, GlcCer(d18:1/26:0)/Total CE, GlcCer(d18:1/26:1)/Total CE, LacCer(d18:1/18:0)/Total PC, LacCer(d18:1/20:0)/PC 16:0/20:3, LacCer(d18:1/20:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 18:0/18:1, LacCer(d18:1/20:0)/PC 18:0/20:3, LacCer(d18:1/20:0)/PC 18:0/20:4, LacCer(d18:1/20:0)/PC 18:1/18:2, LacCer(d18:1/20:0)/SM (d18:1/17:1-OH), LacCer(d18:1/20:0)/SM (d18:1/18:0), LacCer(d18:1/20:0)/Total CE, LacCer(d18:1/20:0)/Total LPC, LacCer(d18:1/20:0)/Total PC, LacCer(d18:1/20:0)/Total SM, LacCer(d18:1/24:0)/Total LPC, PC 16:0/16:0/PC 16:0/20:4, PC 16:0/16:0/Total PC, PC O-32:0 (KDdiA-PC)/Total PC O, PS O-16:0/18:2-alkenyl/Total PC, PS O-16:0/18:2-alkenyl/Total PC O, PS O-16:0/18:2-alkenyl/Total PS O, PS O-16:1/18:2-alkyl/Total PC, PS O-16:1/18:2-alkyl/Total PC O, PS O-16:1/18:2-alkyl/Total PS O, PS O-18:2/16:0-alkenyl/Total PC O, PS O-18:2/16:0-alkenyl/Total PS O, SM (d18:1/17:0) (d18:1/16:1-OH)/Total PC O, Total Cer/Total PC, Total DAG/Total LPC, Total DAG/Total PC, Total DAG/Total PC O and Total LacCer/Total PC;
 
and wherein the one or more lipid-lipid ratio(s) whose decrease(s) is (are) compared to the control is (are) selected from (Tables 5b and 8b):
 
CE 14:0/Cer(d18:1/18:0), CE 14:0/Cer(d18:1/24:1), CE 14:0/Total DAG, CE 15:0/Cer(d18:1/20:0), CE 16:0/Cer(d18:1/18:0), CE 16:0/Cer(d18:1/24:1), CE 16:1/CE 19:1, CE 16:1/Cer(d18:1/18:0), CE 16:1/Cer(d18:1/20:0), CE 16:1/Cer(d18:1/24:1), CE 16:1/GlcCer(d18:1/24:1), CE 16:1/LacCer(d18:1/18:0), CE 16:1/LacCer(d18:1/24:0), CE 16:1/Total LacCer, CE 17:1/Cer(d18:1/18:0), CE 17:1/Cer(d18:1/24:1), CE 18:2/Cer(d18:1/20:0), CE 18:2/Cer(d18:1/24:1), CE 18:3/Cer(d18:1/16:0), CE 18:3/Cer(d18:1/18:0), CE 18:3/Cer(d18:1/20:0), CE 18:3/Cer(d18:1/22:0), CE 18:3/Cer(d18:1/24:0), CE 18:3/Cer(d18:1/24:1), CE 18:3/GlcCer(d18:1/20:0), CE 18:3/LacCer(d18:1/20:0), CE 18:3/LacCer(d18:1/22:0), CE 18:3/LacCer(d18:1/24:0), CE 18:3/PC 16:0/16:0, CE 18:3/PC O-34:1, CE 18:3/PS O-16:0/18:2-alkenyl, CE 18:3/PS O-16:1/18:2-alkyl, CE 18:3/Total CE, CE 18:3/Total Cer, CE 18:3/Total DAG, CE 18:3/Total LacCer, CE 20:3/Cer(d18:1/24:1), CE 20:3/LacCer(d18:1/20:0), CE 20:4/Cer(d18:1/18:0), CE 20:4/Cer(d18:1/24:1), CE 20:4/GlcCer(d18:1/20:0), CE 20:4/GlcCer(d18:1/24:1), CE 20:4/LacCer(d18:1/20:0), CE 20:5/LacCer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/22:0)/Total CE, Cer(d18:0/22:0)/Total DAG, Cer(d18:0/22:0)/Total GlcCer, Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/20:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Total Cer, DAG 16:0/18:1/Total DAG, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), LPC 16:0/LacCer(d18:1/24:0), LPC 18:1/LacCer(d18:1/20:0), LPC 18:2/LacCer(d18:1/20:0), PC 16:0/20:3/PS O-16:0/18:2-alkenyl, PC 16:0/20:3/PS O-16:1/18:2-alkyl, PC 16:0/20:4/PS O-16:0/18:2-alkenyl, PC 16:0/20:4/PS O-16:1/18:2-alkyl, PC 16:0/20:4/Total DAG, PC 18:0/20:3/PS O-16:0/18:2-alkenyl, PC 18:0/20:3/PS O-16:1/18:2-alkyl, PC 18:0/20:3/PS O-18:2/16:0-alkenyl, PC 18:0/20:4/PS O-16:0/18:2-alkenyl, PC 18:0/20:4/PS O-16:1/18:2-alkyl, PC 18:1/18:2/PS O-16:0/18:2-alkenyl, PC 18:1/18:2/PS O-16:1/18:2-alkyl, PC 18:1/18:2/Total Cer, PC O-40:3/PS O-18:2/16:0-alkenyl, SM (d18:1/23:0) (d18:1/22:1-OH)/Total DAG, SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer, Total CE/Total DAG and Total LPC/Total LacCer.
 
         [0069]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid-lipid ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 11): 
       GlcCer(d18:1/26:1)/Total CE, Cer(d18:1/24:1)/Total PC, Cer(d18:1/24:1)/PC 16:0/20:4, Cer(d18:1/20:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 16:0/20:3, Total 
       [0070]    Cer/Total PC, Total LacCer/Total PC, LacCer(d18:1/20:0)/PC 18:1118:2, PS O-16:0/18:2-alkenyl/Total PS O, Cer(d18:1/18:0)/PC 16:0/20:4, LacCer(d18:1/20:0)/Total LPC and LacCer(d18:1/20:0)/PC 16:0/20:4; 
         [0071]    In another preferred embodiment, the one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 11): 
         [0000]    Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/22:0)/Cer(d18:1/24:1), DAG 16:0/18:1/Total DAG, Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/24:0)/Total CE, Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/Total Cer, Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/LacCer(d18:1/24:0), Cer(d18:0/22:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/Cer(d18:1/20:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), Total LPC/Total LacCer and GlcCer(d18:1/26:0)/LacCer(d18:1/22:0). 
         [0072]    In a particularly preferred embodiment, the one or more lipid-lipid ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 13): 
         [0000]    Cer(d18:1/24:1)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 16:0/20:3, PS O-16:0/18:2-alkenyl/Total PS O and Cer(d18:1/18:0)/PC 16:0/20:4;
 
and the one or more lipid-lipid ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 13):
 
GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), DAG 16:0/18:1/Total DAG, Cer(d18:0/24:0)/Total Cer, Total LPC/Total LacCer, GlcCer(d18:1/26:0)/LacCer(d18:1/22:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl and Cer(d18:0/24:0)/LacCer(d18:1/24:0).
 
         [0073]    In yet another embodiment the invention relates to a method of choosing an appropriate treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, comprising determining in a sample from said subject one or more lipid-clinical concentration ratio(s), wherein (an) increased or decreased lipid-clinical concentration ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject being in need of treatment or a change in, or supplementation of, an already administered treatment, wherein the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Tables 6a and 9a): 
         [0000]    Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein B (mg/dL), Cer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total-c/HDL-c, Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/20:0)/apolipoprotein B (mg/dL), Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/22:0)/apolipoprotein B (mg/dL), Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein B (mg/dL), Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total-c/HDL-c, Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), GlcCer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/18:0)/apolipoprotein B (mg/dL), LacCer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/18:0)/total-c/HDL-c, LacCer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/20:0)/apoA1/apoB, LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein B (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL-c/HDL-c, LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/total-c/HDL-c, LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/22:0)/apoA1/apoB, LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein B (mg/dL), LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total-c/HDL-c, LacCer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/24:0)/apoA1/apoB, LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/24:1)/apolipoprotein B (mg/dL), LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), PC O-32:0 (KDdiA-PC)/apolipoprotein A-I (mg/dL), PC O-32:0 (KDdiA-PC)/triglycerides (EDTA) (mg/dL), PC O-34:1/triglycerides (EDTA) (mg/dL), PS O-16:0/18:1-alkenyl (PS O-16:1/18:1-alkyl)/triglycerides (EDTA) (mg/dL), PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL), PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL), PS O-18:2/16:0-alkenyl/HDL cholesterol (EDTA) (mg/dL), PS O-18:2/16:0-alkenyl/triglycerides (EDTA) (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total Cer/total cholesterol (EDTA) (mg/dL), Total Cer/triglycerides (EDTA) (mg/dL), Total GlcCer/apolipoprotein B (mg/dL), Total GlcCer/total cholesterol (EDTA) (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein B (mg/dL), Total LacCer/total cholesterol (EDTA) (mg/dL) and Total LacCer/triglycerides (EDTA) (mg/dL);
 
and wherein the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Tables 6a and 9a):
 
CE 14:0/apolipoprotein B (mg/dL), CE 14:0/LDL cholesterol (EDTA) (mg/dL), CE 14:0/LDL-c/HDL-c, CE 14:0/total cholesterol (EDTA) (mg/dL), CE 14:0/total-c/HDL-c, CE 16:1/apolipoprotein B (mg/dL), CE 16:1/HDL cholesterol (EDTA) (mg/dL), CE 16:1/LDL cholesterol (EDTA) (mg/dL), CE 16:1/total cholesterol (EDTA) (mg/dL), CE 17:1/LDL-c/HDL-c, CE 18:3/apoA1/apoB, CE 18:3/apolipoprotein A-I (mg/dL), CE 18:3/apolipoprotein B (mg/dL), CE 18:3/HDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL-c/HDL-c, CE 18:3/total cholesterol (EDTA) (mg/dL), CE 18:3/total-c/HDL-c, CE 20:3/apolipoprotein B (mg/dL), CE 20:3/LDL-c/HDL-c, CE 20:3/total-c/HDL-c, CE 20:5/apolipoprotein B (mg/dL), CE 20:5/HDL cholesterol (EDTA) (mg/dL), CE 20:5/LDL cholesterol (EDTA) (mg/dL), Cer(d18:0/22:0)/apolipoprotein B (mg/dL), Cer(d18:0/22:0)/LDL-c/HDL-c, Cer(d18:0/22:0)/total-c/HDL-c, Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/LDL-c/HDL-c, Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/total-c/HDL-c, LPC 18:2/apoA1/apoB, LPC 18:2/apolipoprotein B (mg/dL), LPC 18:2/HDL cholesterol (EDTA) (mg/dL), LPC 18:2/LDL cholesterol (EDTA) (mg/dL), LPC 18:2/LDL-c/HDL-c, LPC 18:2/total cholesterol (EDTA) (mg/dL), PC 16:0/20:3/apolipoprotein B (mg/dL), PC 16:0/20:3/HDL cholesterol (EDTA) (mg/dL), PC 16:0/20:3/LDL-c/HDL-c, PC 16:0/20:3/total-c/HDL-c, PC 16:0/20:4/apolipoprotein A-I (mg/dL), PC 16:0/20:4/apolipoprotein B (mg/dL), PC 16:0/20:4/LDL cholesterol (EDTA) (mg/dL), PC 16:0/20:4/LDL-c/HDL-c, PC 16:0/20:4/total cholesterol (EDTA) (mg/dL), PC 16:0/20:4/total-c/HDL-c, PC 18:0/18:1/LDL-c/HDL-c, PC 18:0/20:3/LDL-c/HDL-c, PC 18:0/20:3/total-c/HDL-c, PC 18:0/20:4/apoA1/apoB, Total LPC/LDL-c/HDL-c, Total LPC/total-c/HDL-c, Total PC/apolipoprotein B (mg/dL), Total PC/LDL-c/HDL-c, Total PC/total cholesterol (EDTA) (mg/dL) and Total PC/total-c/HDL-c.
 
         [0074]    In yet another embodiment the invention relates to a method of choosing an appropriate treatment of CVD and/or one or more of its complications, such as AMI or CVD death, in a subject, wherein the subject is not undergoing statin treatment and wherein said method comprises determining in a sample from said subject one or more lipid-clinical concentration ratio(s), wherein (an) increased or decreased lipid-clinical concentration ratio(s) in said sample, when compared to a control sample, is (are) indicative of said subject being in need of treatment or a change in, or supplementation of, an already administered treatment, wherein the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Tables 6b and 9b): 
         [0000]    Cer(d18:1/16:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/16:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein B (mg/dL), Cer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/18:0)/total-c/HDL-c, Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/20:0)/apolipoprotein B (mg/dL), Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/20:0)/total-c/HDL-c, Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/22:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/22:0)/apolipoprotein B (mg/dL), Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL), Cer(d18:1/24:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:0)/apolipoprotein B (mg/dL), Cer(d18:1/24:0)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein B (mg/dL), Cer(d18:1/24:1)/HDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/LDL-c/HDL-c, Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), Cer(d18:1/24:1)/total-c/HDL-c, Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), GlcCer(d18:1/20:0)/apolipoprotein B (mg/dL), GlcCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), GlcCer(d18:1/24:1)/apolipoprotein B (mg/dL), GlcCer(d18:1/26:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/18:0)/apolipoprotein B (mg/dL), LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/apoA1/apoB, LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein B (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/LDL-c/HDL-c, LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/20:0)/total-c/HDL-c, LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL), LacCer(d18:1/22:0)/apoA1/apoB, LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein B (mg/dL), LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL), LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/24:1)/apolipoprotein B (mg/dL), LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL), LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL), PC O-34:1/apolipoprotein B (mg/dL), PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL), PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total Cer/apolipoprotein B (mg/dL), Total Cer/LDL cholesterol (EDTA) (mg/dL), Total Cer/total cholesterol (EDTA) (mg/dL), Total DAG/apolipoprotein A-I (mg/dL), Total DAG/triglycerides (EDTA) (mg/dL), Total GlcCer/apolipoprotein B (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein B (mg/dL) and Total LacCer/total cholesterol (EDTA) (mg/dL).
 
and wherein the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Tables 6b and 9b):
 
CE 14:0/apoA1/apoB, CE 14:0/apolipoprotein B (mg/dL), CE 14:0/LDL-c/HDL-c, CE 14:0/total-c/HDL-c, CE 16:1/apoA1/apoB, CE 18:3/apoA1/apoB, CE 18:3/apolipoprotein A-I (mg/dL), CE 18:3/apolipoprotein B (mg/dL), CE 18:3/HDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL cholesterol (EDTA) (mg/dL), CE 18:3/LDL-c/HDL-c, CE 18:3/total cholesterol (EDTA) (mg/dL), CE 18:3/total-c/HDL-c, CE 20:5/triglycerides (EDTA) (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/total-c/HDL-c, PC 18:0/20:4/apoA1/apoB, PC O-38:6/apolipoprotein A-I (mg/dL), Total LPC/apoA1/apoB and Total PC/apolipoprotein A-I (mg/dL).
 
         [0075]    In a preferred embodiment (for subjects that are either undergoing or not undergoing statin treatment), the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 12): 
         [0000]    Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Total Cer/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) and Cer(d18:1/24:1)/apolipoprotein B (mg/dL). 
         [0076]    In another preferred embodiment, the one or more lipid-clinical concentration ratio(s) whose decrease is (are) compared to the control is (are) selected from (Table 12): 
         [0000]    Cer(d18:0/24:0)/apolipoprotein B (mg/dL), Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL), Cer(d18:0/24:0)/apolipoprotein B (mg/dL), PC 16:0/20:4/apolipoprotein B (mg/dL) and Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL). 
         [0077]    In a particularly preferred embodiment, the one or more lipid-clinical concentration ratio(s) whose increase is (are) compared to the control is (are) selected from (Table 13): 
         [0000]    Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) and Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL). 
         [0078]    For the purposes of the invention, and particularly for lipid-clinical concentration ratios, an Apolipoprotein A-I measurement may alternatively be an Apolipoprotein A-II measurement. 
         [0079]    Claim  5  In one embodiment of the invention, the treatment the effectiveness of which is to be evaluated or which is to be chosen as appropriate in accordance with the methods described and claimed herein, is a lipid modifying treatment. 
         [0080]    Claim  7  For the purposes of the invention, at least one lipid concentration, lipid-lipid ratio or lipid-clinical concentration ratio from Tables 4-13, or combinations thereof, may be determined to assess whether the patient is at risk to develop one or more of CVD complications such as AMI or CVD death; to evaluate the effectiveness of the treatment of CVD and/or one or more of its complications, such as AMI or CVD death in a subject; or to choose an appropriate treatment of CVD and/or one or more of its complications, such as AMI or CVD death in a subject. However, it is also possible, and may be advantageous, to determine at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 lipid concentrations, lipid-lipid ratios or lipid-clinical concentration ratios from Tables 4-13, or combinations thereof, in this regard. Where more than one lipidomic markers are determined and used for the assessment, it may be advantageous that a specific lipid concentration, lipid-lipid ratio, lipid-clinical concentration ratio or combination thereof, is given greater weight than others in the above-mentioned assessment, evaluation or choice. 
         [0081]    Preferred embodiments of the invention are methods wherein the one or more lipid(s) or lipid ratio(s), or combination thereof, comprise(s): (particularly preferred lipid species and ratios in claim  6 ) Cer(d18:1/20:0), LacCer(d18:1/20:0), Cer(d18:1/24:1), LacCer(d18:1/24:1), LacCer(d18:1/22:0), Cer(d18:1/18:0), PC 16:0/20:4, Cer(d18:0/24:0), Cer(d18:1/24:1)/PC 16:0/20:4, LacCer(d18:1/20:0)/PC 16:0/20:3, PS O-16:0/18:2-alkenyl/Total PS O, Cer(d18:1/18:0)/PC 16:0/20:4, GlcCer(d18:1/26:0)/LacCer(d18:1/20:0), DAG 16:0/18:1/Total DAG, Cer(d18:0/24:0)/Total Cer, Total LPC/Total LacCer, GlcCer(d18:1/26:0)/LacCer(d18:1/22:0), Cer(d18:0/24:0)/Cer(d18:1/24:1), Cer(d18:0/24:0)/Cer(d18:1/18:0), Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/24:0)/Cer(d18:1/22:0), Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl, Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl, Cer(d18:0/24:0)/LacCer(d18:1/24:0), Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL), Total LacCer/apolipoprotein A-I (mg/dL), LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) and Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL). 
         [0082]    In the context of the present invention, CVD is typically characterized by coronary artery disease, peripheral artery disease, a stroke and/or CVD death. The CVD in the subject whose sample is analyzed in accordance with the invention may be atherosclerosis-induced. However, the invention also embodies methods involving subjects who are at risk of developing CVD, but who may or may not have atherosclerosis. 
         [0083]    In a further embodiment, the methods of the invention may further comprise determining the serum level of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein B (ApoB) and/or Apolipoprotein C-III in the subject&#39;s sample. In one embodiment of the invention, the subject does not have elevated serum levels of one or more of total cholesterol, low-density lipoprotein cholesterol (LDL-C), Apolipoprotein C-III or Apolipoprotein B (ApoB), or a decreased serum level of HDL-cholesterol (HDL-C). 
         [0084]    As mentioned above, for the purposes of the present invention, a control sample may be obtained from (a) CAD patient(s) or a group of CAD patients that has/have remained free of any major CVD complications e.g., by mixing a variety of samples from said population. If a group of CAD patients is used then several lipid profiles from a population are combined and the lipidomic marker is created from this combination. The levels or amounts of the individual lipids or the lipid-lipid ratios or lipid-clinical concentration ratios in the sample from a subject are compared to the levels or amounts of the lipids or lipid ratios in the control for determining the risk of one or more of CVD complications, such as AMI or CVD death, in said subject. 
         [0085]    The invention encompasses the analysis of lipid concentrations, lipid-lipid ratios and/or lipid-clinical concentration ratios in samples from a subject that has been or is being treated with one or more statins and/or any other HMG-CoA reductase inhibitor. 
         [0086]    Alternatively, the invention encompasses the analysis of lipid concentrations, lipid-lipid ratios and/or lipid-clinical concentration ratios in samples from a subject that has not yet undergone statin therapy or therapy with any other HMG-CoA reductase inhibitor. 
         [0087]    In accordance with the aspects and embodiments of the invention described and claimed herein, the statin may be one selected from the group consisting of atorvastatin, cerivastatin, fluvastatin, fluvastatin XL, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. 
         [0088]    Collecting information on a lipidomic marker or a lipidomic profile from a subject&#39;s biological sample can be performed via various chemical and high resolution analytical techniques. Suitable analytical techniques include but are not limited to mass spectrometry and nuclear resonance spectroscopy. Any high resolution technique capable of resolving individual lipids or lipid classes and providing structural information of the same can be used to collect the lipid profile from the biological sample. For methods of the present invention the level of the lipid is determined by using mass spectrometry, nuclear magnetic resonance spectroscopy, fluorescence spectroscopy or dual polarisation interferometry, a high performance separation method such as HPLC or UPLC and/or an immunoassay such as an ELISA. According to an alternative or further embodiment an analyte in a sample can be detected and/or quantified by combining the analyte with a binding moiety capable of specifically binding the analyte. The binding moiety can include, for example, a member of a ligand-receptor pair, i.e., a pair of molecules capable of having a specific binding interaction. The binding moiety can also include, for example, a member of a specific binding pair, such as antibody-antigen, enzyme-substrate, nucleic acid-based ligands, other protein ligands, or other specific binding pairs known in the art. In a preferred embodiment, the lipidomic profile is collected with mass spectrometry (MS), wherein the MS instrument may be coupled to direct infusion methods and high performance separation methods such as HPLC or HPLC. The amount of the individual lipids or lipid classes in the collected lipidomic profile is used when comparing the collected lipid profile to a control. 
         [0089]    The methods of the present invention may be used for determining a risk of said patient to develop CVD complications, particularly severe CVD complications such as death and myocardial infarction (MI), including acute myocardial infarction (AMI). 
         [0090]    In one embodiment of the invention, a method for treating or preventing CVD complications, such as AMI or CVD death, in a subject in need thereof is provided. The method comprises administering a therapeutically effective dose of a drug capable of modulating one or more of the lipid concentration(s), lipid-lipid ratio(s) or lipid-clinical concentration ratio(s) described in Tables 4-13, wherein the dose is such that said one or more lipid concentration(s), lipid-lipid ratio(s) or lipid-clinical concentration ratio(s) in a sample of said subject does not significantly change when compared to (a) corresponding lipid concentration(s), (a) corresponding lipid-lipid ratio(s) or (a) corresponding lipid-clinical concentration ratio(s) in a control, e.g., a control sample. In a preferred embodiment, the drug is a statin or another HMG CoA reductase inhibitor. Particularly preferred statins in this regard are atorvastatin, cerivastatin, fluvastatin, fluvastatin XL, lovastatin, pitavastatin, pravastatin, rosuvastatin or simvastatin. In another preferred embodiment, the drug is niacin (nicotinic acid); a cholesterol absorption inhibitor, such as ezetimibe or SCH-48461; a cholesteryl ester transfer protein (CETP) inhibitor, such as torcetrapib, anacetrapib or JTT-705; a bile acids sequestrant, such as colesevelam, cholestyramine and colestipol; or a fibrate, such as fenofibrate, gemfibrozil, clofibrate, and bezafibrate. Alternatively, it may also be a phytosterol. 
         [0091]    Also embodied by the present invention is a lipid as described herein, e.g. a lipid from any of Tables 4, 7, 10 or 13, for use in preventing or treating a subject at risk to develop CVD complications such as AMI or CVD death, wherein the said lipid is to be taken as a dietary supplement or a medicament. A corresponding method of treatment is likewise encompassed. Likewise, the invention also encompasses a modulator for use for modulating a lipid concentration, lipid-lipid ratio or lipid-clinical concentration ratio as described herein, e.g., in Tables 4-13, in a subject at risk to develop CVD and/or one or more of its complications such as AMI or CVD death. A corresponding method of treatment is likewise encompassed. In a further embodiment, the said modulator is a small molecule, an antisense RNA, a small interfering RNA (siRNA) or a natural or modified lipid. 
         [0092]    In one embodiment of the present invention, an antibody against any one of the lipids in Tables 4-13 is used for predicting one or more CVD complications such as AMI or CVD death. In another embodiment of the invention, the antibody may be used for preventing or treating one or more of the above complications in a subject. 
         [0093]    Any of the methods, drugs, lipids or antibodies of the present invention may be used for a subject which is at risk to develop or has suffered from one or more CVD complications such as acute myocardial infarction and/or a cardiovascular death. For the purposes of the invention, CVD complication(s) includes severe CVD complication(s), particularly death. 
         [0094]    Also encompassed by the present invention is a kit for predicting CVD complications or for performing any of the methods or uses of the present invention, wherein the kit comprises a lipid standard chosen from the lipids in Tables 4, 7, 10 or 13, one or more control lipidomic markers, an antibody against one of the said lipids, and reagents for performing the method. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0095]      FIG. 1 . 
           [0096]    This FIGURE demonstrates the importance of molecular lipid measurements. Two examples are given in this FIGURE to illustrate that two closely related molecular lipids may have a very different or even opposite effect on CVD complications. First quadrangles are used to indicate two Lactosylceramides (LacCer). LacCer (18:1/20:0) is a significant predictor for CVD Death, while closely related LacCer (18:1/16:0) has only limited or no value as a risk predictor. Second example proves that that two lipid species from the same lipid class may have even an opposite effect on CVD events. PC (18:0/20:4) proved to be a protective lipid against CVD death while PC (16:0/16:0) seems to increase CVD complications. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Definitions 
       [0097]    Coronary vascular disease/cardiovascular disease (CVD) has its general meaning in the art and is used to classify numerous conditions that affect the heart, heart valves, blood, and vasculature of the body, including CAD. In the present invention the terms CVD and CAD may be used interchangeably. Cardiovascular diseases include endothelial dysfunction, coronary artery disease, angina pectoris, myocardial infarction, atherosclerosis, congestive heart failure, hypertension, cerebrovascular disease, stroke, transient ischemic attacks, deep vein thrombosis, peripheral artery disease, cardiomyopathy, arrhythmias, aortic stenosis, and aneurysm. Such diseases frequently involve atherosclerosis. In a preferred embodiment of the invention, the cardiovascular disease is a cardiovascular disease associated with atherosclerosis. 
         [0098]    CAD is coronary artery disease, AMI is acute myocardial infarction, ACS is acute coronary syndrome, CAC is coronary artery calcification, RCT is reverse cholesterol transport, LDL is low density lipoprotein, HDL is high density lipoprotein, LDL-C is low density lipoprotein cholesterol, HDL-C is high density lipoprotein cholesterol, ApoA is Apolipoprotein A, ApoB is Apolipoprotein B, ApoC is apolipoprotein C, MS is mass spectrometry, HPLC is high performance liquid chromatography, and UPLC is ultra performance liquid chromatography. 
         [0099]    As used herein, “a subject” includes all mammals, including without limitation humans, but also non-human primates, dogs, cats, horses, sheep, goats, cows, rabbits, pigs and rodents. 
         [0100]    A “sample” is defined as any biological sample obtained from a subject or a group or population of subjects. For the purposes of the present invention, the biological sample may be whole blood, blood serum, or blood plasma. It may also be a tissue sample. However, a preferred embodiment is wherein the biological sample is plasma or serum. Taking a blood sample of a patient is a part of normal clinical practice. The blood sample can be taken in connection with e.g. measuring the cholesterol levels in the patients. The collected blood sample can be prepared and serum or plasma can be separated with techniques well known to a person skilled in the art. Vena blood samples can be collected from patients using a needle and a BD Vacutainer® Plastic Tubes or Vacutainer® Plus Plastic Tubes (BD Vacutainer® SST™ Tubes contain spray-coated silia and a polymer gel for serum separation). Serum can be separated by centrifugation at 1300 RCF for 10 min at room temperature and stored in small plastic tubes at −80° C. 
         [0101]    For the purposes of the present invention, lipids from the Lipidomic analysis were named according to the following nomenclature: CE is cholesteryl ester, Cer is ceramide, DAG is diacylglycerol, PC O is ether-linked PC, GD is disialogangliosides, GlcCer is galactosyl- and glucosylceramides, GM is monosialogangliosides, LacCer is lactosylceramides, LPC is lysophosphatidylcholine, PC is Phosphatidylcholine, PE is Phosphatidylethanolamine, PI is Phosphatidylinositol, SM is Sphingomyelin, SIP is sphingosine-1-phosphate. 
         [0102]    The nomenclature X:Y indicates, X number of total carbon atoms in the fatty acid(s) portions of the molecule, and Y the total number of double bonds in the fatty acid portion(s) of the molecule. 
         [0103]    The nomenclature A/B indicates, for a molecule of DAG and PC, A and B types of fatty acid moieties attached to the glycerol backbone of the molecule. 
         [0104]    The nomenclature (dC/A) indicates, for a molecule of Cer, GlcCer, LacCer and SM, C the type of long-chain base with an amide-linked, A, fatty acid moiety. 
         [0105]    The wording “compared to a control sample” as used herein will be understood to include embodiments where control samples are actually analyzed in respect of a lipidomic marker of interest, i.e., in respect of the concentration of one or more of the lipid(s), the lipid-lipid ratios, or the lipid-clinical concentration ratios or combinations thereof as specifically described herein in connection with the various aspects and embodiments of the present invention. It will be appreciated, however, that the above wording also includes embodiments where the corresponding information on said lipidomic marker in said control sample is merely taken from the literature, or has been previously determined, calculated or extrapolated, or is yet to be determined, calculated or extrapolated. 
         [0106]    As used herein, the term “antibody” includes monoclonal and polyclonal antibodies, whole antibodies, antibody fragments, and antibody sub-fragments that exhibit specific binding to a said lipid. Thus, suitable “antibodies” can be whole immunoglobulins of any class, e.g., IgG, IgM, IgA, IgD, IgE, chimeric antibodies or hybrid antibodies with dual or multiple antigen or epitope specificities, or fragments, e.g., F(ab′) 2 , Fab′, Fab and the like, including hybrid fragments, and additionally includes any immunoglobulin or any natural, synthetic or genetically engineered protein that acts like an antibody by binding to a specific antigen to form a complex. The term “antibody” encompasses antigen-binding fragments of antibodies (e.g., single chain antibodies, Fab fragments, F(ab) 2 , a Fd fragment, a Fv fragment and dAb fragments) as well as complete antibodies. For example, Fab molecules can be expressed and assembled in a genetically transformed host like  E. coli . A lambda vector system is available thus to express a population of Fab&#39;s with a potential diversity equal to or exceeding that of subject generating the predecessor antibody. See Huse W D, et al.,  Science  1989, 246:1275-81. Such Fab&#39;s are included in the definition of “antibody.” The ability of a given molecule, including an antibody fragment or sub-fragment, to act like an antibody and specifically bind to a specific antigen can be determined by binding assays known in the art, for example, using the antigen of interest as the binding partner. 
         [0107]    Antibodies against lipids in accordance with the present invention may be prepared by methods well known to those skilled in the art. For example, mice may be immunized with a lipid with adjuvant. Splenocytes are harvested as a pool from the mice that were administered 3 immunizations at 2-week intervals with test bleeds performed on alternate weeks for serum antibody titers. Splenocytes are prepared as 3 aliquots that are either used immediately in fusion experiments or stored in liquid nitrogen for use in future fusions. 
         [0108]    Fusion experiments are then performed according to the procedure of Stewart &amp; Fuller,  J. Immunol. Methods  1989, 123:45-53. Supernatants from wells with growing hybrids are screened by enzyme-linked immunosorbent assay (ELISA) for monoclonal antibody (MAb) secretors on 96-well ELISA plates coated with the said lipid. ELISA positive cultures are cloned by limiting dilutions, typically resulting in hybridomas established from single colonies after 2 serial cloning experiments. 
       EXAMPLES 
     Example 1 
     Materials and Methods 
       [0109]    This study is a sub-cohort of the LURK study that is a large scale prospective study on cardiovascular epidemiology. LURIC database contains clinical information over 3000 patients including baseline coronary angiography, clinically used biomarker data and also e.g. CVD mortality data for the follow-up period (3 years). In this biomarker study the inventors compared CAD cases (n=62) that died during the follow-up due to CVD with patients (n=173) having a stable CAD. Subjects with a significant atherosclerosis level in the angiogram but no CVD related death during the follow-up were used as controls, while the case group had similarly a significant atherosclerosis based on the angiography at baseline and in addition they died during the follow-up due to acute cardiovascular events. A statistical analysis was performed separately also for cases (n=48) and controls (n=124) that were not treated with statins. The clinical characteristics are described in Table 1. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Background characteristics for LURIC patients 
               
               
                 analyzed with lipidomics 
               
             
          
           
               
                 Variable 
                 Controls (n = 173) 
                 Cases (n = 62) 
               
               
                   
               
             
          
           
               
                 Age (average) 
                 60 
                 67 
               
               
                 LDL-C (mg/dL) 
                 122 
                 117.5 
               
               
                 HDL-C (mg/dL) 
                 37.2 
                 35.3 
               
               
                 DM2 patients 
                 62 (36%) 
                 36 (58%) 
               
               
                 Hypertensive patients 
                 101 (58%)  
                 39 (63%) 
               
               
                 Lipid lowering users 
                 49 (28%) 
                 14 (23%) 
               
               
                 Smokers (active or quit less than 3 
                 46 (27%) 
                  8 (13%) 
               
               
                 years before sampling) 
               
               
                   
               
             
          
         
       
     
         [0110]    Definition of Cases: All cases had a significant vessel disease (&gt;=20% stenosis) in coronary angiogram and they all died due to CVD during the follow-up. 
         [0111]    Definition of Controls: All controls had a significant vessel disease (&gt;=20% stenosis) in coronary angiogram, but they did not die due to CVD during the follow-up. 
       Example 2 
     Analytical Methods 
     Mass Spectrometry Driven Lipidomics 
       [0112]    Direct infusion coupled to tandem mass spectrometry, i.e. shotgun lipidomics, and two liquid chromatography tandem mass spectrometry (LC-MS/MS) approaches, i.e. ceramide and cerebroside lipidomics and ganglioside lipidomics, were used to identify lipid biomarkers for coronary artery disease (CVD) risk by analyzing molecular lipid species in human serum, plasma, and carotid artery plaques. The applied methods were optimized especially for quantification of molecular cholesteryl esters (CE), phosphatidylcholines (PC), lysophosphatidylcholines (LPC) and other lysophospholipids (LPL), ether-linked phosphatidylcholines (PC O) and other ether-linked phospholipids (PL O), phosphatidylserines (PS), phosphatidylethanolamines (PE), phosphatidylglycerols (PG), phosphatidylinositols (PI), phosphatidic acids (PA), diacylglycerols (DAG), ceramides (Cer), glucosylceramides (GlcCer) and lactosylceramides (LacCer). 
         [0113]    The following materials were used according to the methods. HPLC or LC-MS grade of chloroform, methanol, water, acetonitrile, formic acid, methanol, isopropanol, ammonium acetate, acetic acid, potassium chloride and butylated hydroxytoluene (BHT) were purchased from Sigma-Aldrich (St. Louis, Mo., USA). 
         [0114]    HPLC column (Acquity BEH C18, 2.1×50 mm id. 1.7 μm) was purchased from Waters (Milford, Mass., USA). HPLC pre-column (Widepore C18 4×2.0 mm) was purchased from Phenomenex (Torrance, Calif., USA). All labware used for the extraction were resistant to chloroform. Aerosol resistant filter tips (Molecular BioProducts) and Eppendorf 2 ml safe-lock tubes, 96-well twin.tec PCR plates, and Pierce-it-lite thermo-sealing foils were purchased from VWR International (West Chester, Pa., USA). CO-RE Filter Tips and 96-well 2 ml Whatman Uniplates were purchased from Hamilton Robotics (Bonaduz, Switzerland). Synthetic lipid standards were purchased from Avanti Polar Lipids (Alabaster, Ala., USA) and from Matreya (Pleasant Gap, PA, USA). 
         [0115]    Lipids were extracted in chloroform:methanol according to the following protocols. Samples were spiked with known amounts of non-endogenous synthetic internal standards for data normalization and endogenous lipid quantification. In shotgun lipidomics analysis; LPC 17:0, PC 17:0/17:0, PA 17:0/17:0, PE 17:0/17:0, PG 17:0/17:0, PS 17:0/17:0, DAG 17:0/17:0, D6-CE 18:0, in ceramide and cerebroside lipidomics; Cer d18:1/17:0, D3-LacCer d18:1/16:0, and D3-GlcCer d18:1/16:0, were used as internal standards. Post-extract spiked non-endogenous synthetic external standards were used for quality controlling. Stock solutions of standards were prepared by dissolving appropriately weighed amounts of each standard in chloroform:methanol (2:1, V:V) to achieve a final concentration of 500 μM. An internal standard mixture containing each of the standard stock was created and used in lipid extraction. 
         [0116]    Samples and quality control samples for each extraction batch were thawed on ice. The carotid artery plaque samples were weighed on ice by using a cryo-box and homogenized in ice-cold 70% methanol in water. The Mixer Mill 301 Teflon adapters were kept at −20° C. Homogenization was performed at 15-25 Hz for 2-15 minutes with Mixer Mill 301 (Retch GmbH, Germany). 
         [0117]    Lipid extraction of human samples was carried out in automated fashion using a Hamilton MICROLAB STAR system (Hamilton Robotics, Switzerland). Well-mixed samples were aliquoted into a 96-well 2 ml Whatman Uniplate containing ice-cold methanol and 0.1% BHT. 5 μl of serum and plasma and 30 μl of carotid artery plaques were used for shotgun- and ceramide and cerebroside lipidomics and 100 μl of serum and plasma and 200 μl of carotid artery plaques was used for ganglioside lipidomics. The samples were mixed thoroughly after each step in the extraction protocol. The extraction proceeded at room temperature by adding an appropriate volume of internal standard mixture and chloroform, and methanol and water in the case of ganglioside lipidomics. In shotgun and ceramide and cerebroside lipidomics, the organic phase separation was facilitated by adding 20 mM acetic acid and centrifuging the plate for 5 min at 500×g. The organic phase was transferred into a new 96-well 2 ml Whatman Uniplate. The remaining water-containing phase was washed by adding appropriate volume of chloroform followed by centrifugation. The two organic phases were pooled and evaporated under N 2  until dryness. The lipid extracts were then re-dissolved in chloroform:methanol (1:2, v:v) including the addition of the synthetic external standard. In ganglioside lipidomics, after thorough mixing the supernatant was collected after 30 min centrifugation at 2000×g. The remaining pellet was re-extracted with appropriate volume of water and chloroform:methanol (1:2, v:v) and the supernatant was collected in the same way as above. The pooled supernatant was subjected to solvent partitioning by addition of water and inversion of the sample tubes. The upper phase was collected after 30 min centrifugation at 2000×g. The lower phase was thoroughly re-extracted with potassium chloride and the produced upper phase was collected as mentioned above. The upper phases were pooled and evaporated under N 2  until dryness. The lipid extracts were then re-dissolved in chloroform:methanol (1:2, v:v). The extracts were stored in 2 ml safe-lock Eppendorf tubes at −20° C. prior to MS analysis. Required volumes of lipid extracts were aliquoted into an Eppendorf 96-well twin.tec PCR plate and the plate was heat-sealed with aluminum foil to avoid evaporation. 
         [0118]    In shotgun lipidomics, lipid extracts were analyzed on a hybrid triple quadrupole/linear ion trap mass spectrometer (QTRAP 5500, AB Sciex) equipped with a robotic nanoflow ion source (NanoMate HD, Advion Biosciences). The instruments were operated in positive and negative ion modes. In positive ion the spray voltage was set to 1.0 to 1.4 kV and in negative ion mode to −1.0 to −1.4 kV. A gas pressure of 0.3-0.8 psi was used and the interface heater was set at 60° C. The collision energy (CE) and declustering potential (DP) was optimized for each lipid class using synthetic standards. The mass spectrometer was operated in unit resolution mode using a scan speed of 200 Da/s. Molecular lipids were analyzed in both positive and negative ion modes using multiple precursor ion scanning (MPIS) and neutral loss scanning (NLS). The used precursor ion and neutral loss scans in positive mode and negative mode are summarized in Table 2. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Shotgun lipidomics. 
               
             
          
           
               
                 Lipid Class 
                 Characteristic Fragment 
                   
               
               
                   
               
               
                   
                   
                 PIS or NL 
               
               
                   
                   
                 [M + H] +  (m/z) 
               
               
                 PC/SM/LPC 
                 Phosphorylcholine 
                 184.1 
               
               
                 DAG 
                 FA 14:1 
                 283.25 
               
               
                 DAG 
                 FA 14:0 
                 285.25 
               
               
                 DAG 
                 FA 16:2 
                 309.25 
               
               
                 DAG 
                 FA 16:1 
                 311.25 
               
               
                 DAG 
                 FA 16:0 
                 313.25 
               
               
                 DAG 
                 FA 17:0 
                 327.25 
               
               
                 DAG 
                 FA 18:3 
                 335.25 
               
               
                 DAG 
                 FA 18:2 
                 337.25 
               
               
                 DAG 
                 FA 18:1 
                 339.25 
               
               
                 DAG 
                 FA 18:0 
                 341.25 
               
               
                 DAG 
                 FA 20:5 
                 359.25 
               
               
                 DAG 
                 FA 20:4 
                 361.25 
               
               
                 DAG 
                 FA 20:3 
                 363.25 
               
               
                 DAG 
                 FA 20:2 
                 365.25 
               
               
                 DAG 
                 FA 20:1 
                 367.25 
               
               
                 CE 
                 Cholestadiene 
                 369.35 
               
               
                 d6-CE 
                 d6-Cholestadiene 
                 375.35 
               
               
                 DAG 
                 FA 22:6 
                 385.30 
               
               
                 DAG 
                 FA 22:5 
                 387.30 
               
               
                 DAG 
                 FA 22:4 
                 389.30 
               
               
                 DAG 
                 FA 22:3 
                 391.30 
               
               
                 PE/PE-O 
                 phosphorylethanolamine 
                 NL 141.0 
               
               
                 PS 
                 phosphorylserine 
                 NL 185.0 
               
               
                 PG 
                 phosphorylglycerol +NH 4   
                 NL 189.0 
               
               
                 PI 
                 phosphorylinositol +NH 4   
                 NL 277.1 
               
               
                   
                   
                 PIS or NL 
               
               
                   
                   
                 [M − H] −  (m/z) 
               
               
                 PA/PG/PS/PI 
                 Glycerophosphate −H 2 0 
                 153.000 
               
               
                 PC/LPC 
                 Phosphorylcholine 
                 168.000 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 10:1 
                 169.100 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 10:0 
                 171.100 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 11:1 
                 183.100 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 11:0 
                 185.200 
               
               
                 PE 
                 dilyso PE −H 2 0 
                 196.000 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 12:1 
                 197.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 12:0 
                 199.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 13:1 
                 211.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 13:0 
                 213.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 14:2 
                 223.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 14:1 
                 225.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 14:0 
                 227.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 15:2, O-16:2 
                 237.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 15:1, O-16:1 
                 239.200 
               
               
                 PI 
                 PI-H 2 O 
                 241.000 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 15:0 
                 241.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 16:2 
                 251.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 16:1 
                 253.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 16:0 
                 255.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:5-CO 2   
                 257.200 
               
               
                 PC/LPC 
                 D3-FA 16:0 
                 258.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:4-CO 2   
                 259.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 17:2 
                 265.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 O-18:2 
                 265.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 17:1 
                 267.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 17:0 
                 269.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 18:3 
                 277.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 18:2 
                 279.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 18:1 
                 281.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 18:0 
                 283.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:5-CO 2   
                 285.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:4-CO 2   
                 287.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 19:2 
                 293.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 19:1 
                 295.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 19:0 
                 297.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:5 
                 301.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:4 
                 303.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:3 
                 305.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:2 
                 307.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:1 
                 309.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 20:0 
                 311.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:6 
                 327.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:5 
                 329.200 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:4 
                 331.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:3 
                 333.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:2 
                 335.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:1 
                 337.300 
               
               
                 PA/PG/PS/PI/PC/LPC 
                 FA 22:0 
                 339.300 
               
               
                 SGalCer 
                 HSO 4   
                 96.9 
               
               
                 PS 
                 Serine −H 2 O 
                 NL 87.1 
               
               
                   
               
             
          
         
       
     
         [0119]    In ceramide and cerebroside lipidomics, the high performance liquid chromatography (HPLC) analyses were conducted in the following way. Chromatographic apparatus consisted of a CTC HTC PAL autosampler (CTC Analytics AG, Switzerland), a Rheos Allegro UHPLC pump (Flux Instruments AG, Switzerland), an external column heater set to 60° C. for ceramide and cerebroside lipidomics and 45° C. for ganglioside lipidomics, and the Acquity BEH C18 column with an in-line pre-column. The extracted samples, 10 μl of each, were injected into the pre-column followed by the analytical column and delivered to the mass spectrometer at a flow rate of 500 μl/min In ceramide and cerebroside lipidomics, A gradient was used for lipid analyte separation with solvent A comprising 10 mM ammonium acetate in HPLC grade water containing 0.1% formic acid and solvent B of 10 mM ammonium acetate in acetonitrile:isopropanol (4:3, V:V) containing 0.1% formic acid. The gradient was constructed in the following way: 0 min—65% B; 2 min—65% B; 2.5 min—75% B; 17.5 min—100% B; 22.5 min—100% B; 22.6 min—65% B; 25 min—65% B. 
         [0120]    The lipid extracts were analyzed by HPLC-MS/MS. The MS analysis was performed on a hybrid triple quadrupole/linear ion trap mass spectrometer equipped with the Turbo V™ Ion Source (4000 QTRAP, AB Sciex). The instrument was operating in positive and negative ion modes. The ion source voltage was set to 5500V for ceramide and cerebroside lipidomics and to −4500V for ganglioside lipidomics, and source temperature at 400° C. The collision energy (CE) and declustering potential (DP) was optimized for each lipid class using synthetic standards. A 20 sec dwell time was applied for each scan. Multiple reaction monitoring (MRM) scan mode was used. MRM transitions for each lipid species are summarized in table 3. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Ceramide and cerebroside lipidomics. 
               
             
          
           
               
                 Lipid 
                 [M + H] +  (m/z) 
                 Product [M + H] +  (m/z) 
               
               
                   
               
             
          
           
               
                 Cer(d18:0/16:0) 
                 540.5 
                 266.25 
               
               
                 Cer(d18:0/18:0) 
                 568.6 
                 266.25 
               
               
                 Cer(d18:0/20:0) 
                 596.6 
                 266.25 
               
               
                 Cer(d18:0/22:0) 
                 624.6 
                 266.25 
               
               
                 Cer(d18:0/24:0) 
                 652.7 
                 266.25 
               
               
                 Cer(d18:0/24:1) 
                 650.6 
                 266.25 
               
               
                 Cer(d18:0/26:0) 
                 680.7 
                 266.25 
               
               
                 Cer(d18:0/26:1) 
                 678.7 
                 266.25 
               
               
                 Cer(d18:1/16:0) 
                 538.5 
                 264.25 
               
               
                 Cer(d18:1/18:0) 
                 566.5 
                 264.25 
               
               
                 Cer(d18:1/20:0) 
                 594.6 
                 264.25 
               
               
                 Cer(d18:1/22:0) 
                 622.6 
                 264.25 
               
               
                 Cer(d18:1/24:0) 
                 650.6 
                 264.25 
               
               
                 Cer(d18:1/24:1) 
                 648.6 
                 264.25 
               
               
                 Cer(d18:1/26:0) 
                 678.7 
                 264.25 
               
               
                 Cer(d18:1/26:1) 
                 676.7 
                 264.25 
               
               
                 GlcCer(d18:0/16:0) 
                 702.6 
                 266.25 
               
               
                 GlcCer(d18:0/18:0) 
                 730.6 
                 266.25 
               
               
                 GlcCer(d18:0/20:0) 
                 758.6 
                 266.25 
               
               
                 GlcCer(d18:0/22:0) 
                 786.7 
                 266.25 
               
               
                 GlcCer(d18:0/24:0) 
                 814.7 
                 266.25 
               
               
                 GlcCer(d18:0/24:1) 
                 812.7 
                 266.25 
               
               
                 GlcCer(d18:0/26:0) 
                 842.7 
                 266.25 
               
               
                 GlcCer(d18:0/26:1) 
                 840.7 
                 266.25 
               
               
                 GlcCer(d18:1/16:0) 
                 700.6 
                 264.25 
               
               
                 GlcCer(d18:1/18:0) 
                 728.6 
                 264.25 
               
               
                 GlcCer(d18:1/20:0) 
                 756.6 
                 264.25 
               
               
                 GlcCer(d18:1/22:0) 
                 784.7 
                 264.25 
               
               
                 GlcCer(d18:1/24:0) 
                 812.7 
                 264.25 
               
               
                 GlcCer(d18:1/24:1) 
                 810.7 
                 264.25 
               
               
                 GlcCer(d18:1/26:0) 
                 840.7 
                 264.25 
               
               
                 GlcCer(d18:1/26:1) 
                 838.7 
                 264.25 
               
               
                 LacCer(d18:1/16:0) 
                 862.6 
                 264.25 
               
               
                 LacCer(d18:1/18:0) 
                 890.7 
                 264.25 
               
               
                 LacCer(d18:1/20:0) 
                 918.7 
                 264.25 
               
               
                 LacCer(d18:1/22:0) 
                 946.7 
                 264.25 
               
               
                 LacCer(d18:1/24:0) 
                 974.7 
                 264.25 
               
               
                 LacCer(d18:1/24:1) 
                 972.7 
                 264.25 
               
               
                 LacCer(d18:1/26:0) 
                 1002.8 
                 264.25 
               
               
                 LacCer(d18:1/26:1) 
                 1000.8 
                 264.25 
               
               
                 LacCer(d18:0/16:0) 
                 864.6 
                 266.25 
               
               
                 LacCer(d18:0/18:0) 
                 892.7 
                 266.25 
               
               
                 LacCer(d18:0/20:0) 
                 920.7 
                 266.25 
               
               
                 LacCer(d18:0/22:0) 
                 948.7 
                 266.25 
               
               
                 LacCer(d18:0/24:0) 
                 976.7 
                 266.25 
               
               
                 LacCer(d18:0/24:1) 
                 974.7 
                 266.25 
               
               
                 LacCer(d18:0/26:0) 
                 1004.8 
                 266.25 
               
               
                 LacCer(d18:0/26:1) 
                 1002.8 
                 266.25 
               
               
                 Cer(d18:1/16:0)-OH 
                 554.5 
                 264.25 
               
               
                 Cer(d18:1/18:0)-OH 
                 582.5 
                 264.25 
               
               
                 Cer(d18:1/20:0)-OH 
                 610.6 
                 264.25 
               
               
                 Cer(d18:1/22:0)-OH 
                 638.6 
                 264.25 
               
               
                 Cer(d18:1/24:0)-OH 
                 666.6 
                 264.25 
               
               
                 Cer(d18:1/24:1)-OH 
                 664.6 
                 264.25 
               
               
                 Cer(d18:1/26:0)-OH 
                 694.7 
                 264.25 
               
               
                 Cer(d18:1/26:1)-OH 
                 692.7 
                 264.25 
               
               
                 IS D3-LacCer d18:1/16:0 
                 865.6 
                 264.25 
               
               
                 IS D3-GluCer d18:1/16:0 
                 703.7 
                 264.25 
               
               
                 IS Cer d18:1/17:0 
                 552.5 
                 264.25 
               
               
                 ES Cer d17:1/18:0 
                 552.5 
                 250.25 
               
               
                   
               
             
          
         
       
     
         [0121]    The data processing was done in the following way. Initially the retention time (in LC mode) and identification of each peak was done using endogenous standards and by Information Dependent Acquisition (IDA) experiments where applicable. The raw data were processed according to peak detected and retention time (in LC mode) in automated fashion. A stringent cutoff was applied for separating background noise from actual lipid peaks. Each sample was controlled and only accepted when fulfilling the stringent acceptance criteria. Peak area counts (cps) of detected peaks were converted into a list of corresponding lipid names. Lipids were normalized to their respective internal standard and sample volume or tissue weight to retrieve their concentrations. 
         [0122]    Several quality controls were used in the lipidomic analyses. A calibration line using synthetic or isolated standards was obtained prior to sample analysis. Synthetic standards were chosen based on application and had similar properties to the endogenous lipids or analyte(s) of interest. The calibration line consisted of a minimum of five standards points covering the expected quantification range. A sample extracted without standard and standards extracted with no matrix, were included with the calibration line. 
         [0123]    The calibration line was used to determine the dynamic quantification range for each lipid class monitored, e.g., the linear quantification limits. As the internal standards used behave in the same way as endogenous lipids they were used for quantifying endogenous lipid species. The calibration lines were based on the same internal standards that were used for quantification of the endogenous lipids. 
         [0124]    In each sample extracted for lipids, the ratio of synthetic internal standards (IS) to corresponding post-extract spiked external standard (ES) was determined. The peak area (cps) ratio of internal to external standard (IS/ES) was used for calculating the Coefficient of Variation (CV) across all samples. The IS/ES ratio enabled the calculation of lipid extraction recovery. 
         [0125]    Instrument control (IC) was included at the start, middle and end of each run. IC sample analyzed was an extracted reference plasma sample and a set of standards to monitor the instrument&#39;s performance, i.e., the intra- and inter-assay variation. 
         [0126]    For each platform, a stringent cutoff was applied for separating background noise from actual lipid peaks. Each sample was controlled and only accepted when fulfilling the stringent acceptance criteria. Masses and counts of detected peaks were converted into a list of corresponding lipid names. Lipids were normalized to their respective internal standard and sample volume to retrieve their concentrations. 
       Statistical Analyses 
       [0127]    Percentage changes in lipid concentrations between control and case groups were calculated as follows: 
         [0000]      100*(AVG[ C ] in case group−AVG[ C ] in control group)/AVG[ C ] in control group
 
         [0000]    Statistical significance was assigned based on standard t-test p-values. 
         [0128]    In addition, ROC curves were used for finding lipid molecules and concentration cutoffs that separate the best cases from controls. Selectivity is calculated as a number of correctly identified cases divided by the total number of cases. Specificity is calculated as a number of correctly identified controls divided by the total number of controls. Selectivity and specificity was calculated for each lipid concentration, lipid to lipid ratio and ratio of lipid to clinical concentrations. 
       Example 3 
     Ethics 
       [0129]    The LURIC study was approved by the ethics review committee at the “Landesärztekammer Rheinland-Pfalz” (Mainz, Germany). Written informed consent was obtained from each of the participants. 
       Results 
       [0130]    In this LURIC study sub-cohort, the traditional biomarkers including LDL-cholesterol and HDL-cholesterol concentrations were practically identical in both groups and therefore were not predictive of CVD-related mortality in this study. 
         [0131]    Multiple lipidomic markers appeared as significant predictors of CVD death (Tables 4-13). A total of 151 molecular lipids were quantified. The significant predictors were selected based on the top fifty candidates from each category, when available. The biomarker candidates based on molecular lipid concentrations are presented in Tables 4, 7, 10 and 13. The candidates were selected according to the following criteria: t-test p-value ≦0.05 or sensitivity ≧60% and specificity ≧60%. From traditional clinical chemistry only apolipoprotein A1 and total cholesterol reached statistical significance with p-value lower than 0.05, but % change was less than 10% between controls and cases, other clinical values did not show any statistical significance. The predictive value of new lipidomic biomarkers was increased when their levels were expressed as distinct lipid-lipid ratios or lipid-clinical ratios (e.g. LDL-C or HDL-C). The top biomarker candidates are presented in Table 13. Top candidates from each category, when available, were selected based on the following selection criteria: t-test p-value ≦0.05 and sensitivity ≧60% and specificity ≧60%. 
       Importance of Detailed Molecular Lipid Analyses 
       [0132]    Recent evolvement of mass spectrometry driven lipid analysis approaches has made it possible to resolve complex lipidomes to their molecular lipid species level at high-throughput and quality required for analyses of clinical cohorts. As a result of the high sensitivity and selectivity of the methods, a lipidome-wide analysis of minute sample amounts has become feasible. Present technologies are capable of identifying lipids with different sum compositions, i.e. phosphatidylcholine (PC) 34:1, but more important is the identification of molecular lipid species, e.g. PC 16:0/18:1. In the latter analysis, information of the type of fatty acids and their positions attached to the glycerol backbone making up the particular PC molecule is retrieved. 
         [0133]    The seminal work of Shinzawa-Itoh and colleagues showed by highly sophisticated experiments that the oxygen transfer mechanism in cytochrome c oxidase requires a specific phosphatidylglycerol molecular lipid with palmitate and vaccenate at the sn-1 and sn-2 positions respectively on the glycerol backbone (Shinzawa-Itoh K, Aoyama H, Muramoto K et al:  Structures and physiological roles of  13  integral lipids of bovine heart cytochrome c oxidase. EMBO  J 2007, 26:1713-1725). In line with other studies, this undoubtedly indicates that the lipid structure is an essential determinant of the biological effect. Therefore, molecular lipidomics is an essential for biomarker discovery.  FIG. 1  illustrates the importance of molecular lipid data by comparing the biomarker value of two PC and LacCer molecules in predicting CVD mortality in the LURIC cohort. The data reveals that while LacCer(d18:1/20:0) is a significant CVD predictor, LacCer (d18:1/18:16:0) has low biomarker potential. In addition, two PC molecules PC (18:0/20:4) and PC (18:0/16:0) have even opposite effects on CVD complications. Thus, it is always necessary to identify and quantify all lipid species for lipid classes of interest including but not limited to cholesterol esters, different phopsholipid classes, ceramides, cerebro sides (lactosylceramides, glycosylceramides), and gangliosides. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Significant lipids in LURIC study sorted by p-value. Lipid 
               
               
                 names, p-values and % change for negative correlation are 
               
               
                 presented. Table 4a shows significant lipids from all study 
               
               
                 subjects. The significant lipids from subjects not undergoing 
               
               
                 statin treatment are listed in table 4b. 
               
             
          
           
               
                   
                   
                   
                 Percentage 
               
               
                   
                 Lipid name 
                 p-value 
                 change 
               
               
                   
                   
               
             
          
           
               
                 4a) Significant lipids in LURIC study sorted by p-value 
               
               
                 from all study subjects. 
               
             
          
           
               
                   
                 Positive correlation 
                   
                   
               
               
                   
                 LacCer(d18:1/20:0) 
                 0.00008 
                 29.52421 
               
               
                   
                 LacCer(d18:1/22:0) 
                 0.00046 
                 22.75541 
               
               
                   
                 LacCer(d18:1/18:0) 
                 0.00094 
                 26.78692 
               
               
                   
                 Cer(d18:1/18:0) 
                 0.00177 
                 23.30373 
               
               
                   
                 Cer(d18:1/20:0) 
                 0.00302 
                 17.32385 
               
               
                   
                 LacCer(d18:1/24:1) 
                 0.00361 
                 24.72456 
               
               
                   
                 PS O-18:2/16:0-alkenyl 
                 0.00571 
                 49.89286 
               
               
                   
                 PS O-16:0/18:2-alkenyl 
                 0.00670 
                 49.99084 
               
               
                   
                 PS O-16:1/18:2-alkyl 
                 0.00670 
                 49.99084 
               
               
                   
                 Cer(d18:1/24:1) 
                 0.01142 
                 14.88898 
               
               
                   
                 Total LacCer 
                 0.01669 
                 13.83938 
               
               
                   
                 PS O-18:0/18:2-alkenyl 
                 0.02899 
                 40.93773 
               
               
                   
                 (PS O-18:1/18:2-alkyl) 
               
               
                   
                 LacCer(d18:1/24:0) 
                 0.04425 
                 15.80958 
               
               
                   
                 PC O-32:0 (KDdiA-PC) 
                 0.04546 
                 17.40815 
               
               
                   
                 GlcCer(d18:1/18:0) 
                 0.04913 
                 12.83156 
               
               
                   
                 Negative correlation 
               
               
                   
                 Total PC 
                 0.00011 
                 −16.07367 
               
               
                   
                 PC 16:0/20:4 
                 0.00077 
                 −18.06547 
               
               
                   
                 Total LPC 
                 0.00126 
                 −17.02070 
               
               
                   
                 CE 14:0 
                 0.00181 
                 −22.73309 
               
               
                   
                 PC 16:0/20:3 
                 0.00191 
                 −18.78110 
               
               
                   
                 Cer(d18:0/24:0) 
                 0.00254 
                 −27.27562 
               
               
                   
                 PC 18:0/20:4 
                 0.00303 
                 −16.02110 
               
               
                   
                 CE 20:3 
                 0.00312 
                 −19.02446 
               
               
                   
                 CE 17:1 
                 0.00694 
                 −16.90145 
               
               
                   
                 PC 18:0/20:3 
                 0.00726 
                 −17.20664 
               
               
                   
                 PC 18:0/18:1 
                 0.00765 
                 −18.18002 
               
               
                   
                 Cer(d18:0/22:0) 
                 0.01158 
                 −22.37263 
               
               
                   
                 PC 16:0/22:6 
                 0.01180 
                 −16.65050 
               
               
                   
                 LPC 18:1 
                 0.01457 
                 −14.45827 
               
               
                   
                 SM (d18:1/23:0) (d18:1/22:1-OH) 
                 0.01920 
                 −14.02360 
               
               
                   
                 CE 16:0 
                 0.02427 
                 −10.63490 
               
               
                   
                 Total CE 
                 0.02745 
                 −11.83333 
               
               
                   
                 SM (d18:1/24:0) (d18:1/23:1-OH) 
                 0.02784 
                 −13.83715 
               
               
                   
                 PC 18:1/18:2 
                 0.03666 
                 −10.83371 
               
             
          
           
               
                 4b) Significant lipids in LURIC study sorted by p-value 
               
               
                 from subjects not undergoing statin treatment. 
               
             
          
           
               
                   
                 Positive correlation 
                   
                   
               
               
                   
                 Cer(d18:1/20:0) 
                 0.00004 
                 28.00357 
               
               
                   
                 Cer(d18:1/18:0) 
                 0.00009 
                 34.32550 
               
               
                   
                 LacCer(d18:1/20:0) 
                 0.00010 
                 32.91154 
               
               
                   
                 Cer(d18:1/24:1) 
                 0.00039 
                 23.37606 
               
               
                   
                 LacCer(d18:1/22:0) 
                 0.00048 
                 25.61851 
               
               
                   
                 LacCer(d18:1/18:0) 
                 0.00144 
                 29.19850 
               
               
                   
                 LacCer(d18:1/24:1) 
                 0.00199 
                 29.83279 
               
               
                   
                 PS O-18:2/16:0-alkenyl 
                 0.00432 
                 33.81177 
               
               
                   
                 Cer(d18:1/22:0) 
                 0.00473 
                 18.32126 
               
               
                   
                 PS O-16:0/18:2-alkenyl 
                 0.00590 
                 32.17190 
               
               
                   
                 PS O-16:1/18:2-alkyl 
                 0.00590 
                 32.17190 
               
               
                   
                 Total DAG 
                 0.00794 
                 31.67365 
               
               
                   
                 Cer(d18:1/16:0) 
                 0.00952 
                 16.71359 
               
               
                   
                 Total Cer 
                 0.00932 
                 15.44601 
               
               
                   
                 Total LacCer 
                 0.01105 
                 16.00541 
               
               
                   
                 LacCer(d18:1/24:0) 
                 0.01989 
                 19.85622 
               
               
                   
                 GlcCer(d18:1/20:0) 
                 0.02288 
                 17.74772 
               
               
                   
                 PC O-32:0 (KDdiA-PC) 
                 0.02467 
                 22.23265 
               
               
                   
                 GlcCer(d18:1/18:0) 
                 0.02584 
                 16.12961 
               
               
                   
                 GlcCer(d18:1/24:1) 
                 0.03290 
                 18.89331 
               
               
                   
                 GlcCer(d18:1/26:1) 
                 0.04702 
                 17.52675 
               
               
                   
                 Cer(d18:1/26:1) 
                 0.04802 
                 13.59618 
               
               
                   
                 Negative correlation 
               
               
                   
                 Total PC 
                 0.00921 
                 −12.44220 
               
               
                   
                 CE 14:0 
                 0.01090 
                 −21.01258 
               
               
                   
                 CE 20:3 
                 0.02157 
                 −16.03606 
               
               
                   
                 CE 17:1 
                 0.02204 
                 −15.93952 
               
               
                   
                 PC 16:0/20:4 
                 0.02256 
                 −14.96966 
               
               
                   
                 PC 18:0/20:4 
                 0.03376 
                 −13.60917 
               
               
                   
                 Cer(d18:0/24:0) 
                 0.03376 
                 −21.87004 
               
               
                   
                 Total LPC 
                 0.03443 
                 −12.91576 
               
               
                   
                 PC 16:0/20:3 
                 0.04337 
                 −13.43056 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
             
               
               
               
             
               
             
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Table of significant lipid to lipid ratios in LURIC study sorted 
               
               
                 by p-value. Lipid names, p-values, % change both for positive 
               
               
                 and negative correlation are presented. Table 5a shows 
               
               
                 significant lipids from all study subjects. The significant 
               
               
                 lipids from subjects not undergoing statin treatment are listed 
               
               
                 in table 5b. 
               
             
          
           
               
                   
                   
                 Percentage 
               
               
                 Lipid name/lipid name 
                 p-value 
                 change 
               
               
                   
               
             
          
           
               
                 5a) Significant lipid to lipid ratios in LURIC study sorted by 
               
               
                 p-value from all study subjects. 
               
             
          
           
               
                 Positive correlation 
                   
                   
               
               
                 GlcCer(d18:1/26:0)/Total CE 
                 0.0000000 
                 12.8050228 
               
               
                 GlcCer(d18:1/26:1)/Total CE 
                 0.0000000 
                 29.5576923 
               
               
                 PS O-16:0/18:2-alkenyl/Total PS O 
                 0.0000000 
                 26.0723978 
               
               
                 PS O-16:1/18:2-alkyl/Total PS O 
                 0.0000000 
                 26.0723978 
               
               
                 PS O-18:2/16:0-alkenyl/Total PS O 
                 0.0000000 
                 28.7826715 
               
               
                 Cer(d18:1/24:1)/Total PC 
                 0.0000000 
                 38.6612692 
               
               
                 PC 16:0/16:0/Total PC 
                 0.0000000 
                 26.1328496 
               
               
                 LacCer(d18:1/20:0)/Total PC 
                 0.0000000 
                 55.3076855 
               
               
                 Cer(d18:1/24:1)/PC 16:0/20:4 
                 0.0000000 
                 52.6701270 
               
               
                 Cer(d18:1/20:0)/Total PC 
                 0.0000000 
                 40.0940286 
               
               
                 LacCer(d18:1/18:0)/Total PC 
                 0.0000000 
                 53.5855166 
               
               
                 Cer(d18:1/18:0)/Total PC 
                 0.0000000 
                 48.2586905 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:4 
                 0.0000000 
                 65.7060860 
               
               
                 Cer(d18:1/24:1)/PC 16:0/18:1 
                 0.0000000 
                 34.2415459 
               
               
                 PS O-18:0/18:2-alkenyl 
                 0.0000000 
                 18.7146206 
               
               
                 (PS O-18:1/18:2-alkyl)/Total PS O 
               
               
                 Total LacCer/Total PC 
                 0.0000001 
                 40.0389043 
               
               
                 Cer(d18:1/24:1)/PC 16:0/20:3 
                 0.0000001 
                 39.6033049 
               
               
                 Cer(d18:1/22:0)/Total PC 
                 0.0000001 
                 31.3604924 
               
               
                 Cer(d18:1/20:0)/PC 16:0/20:4 
                 0.0000001 
                 55.6619154 
               
               
                 LacCer(d18:1/22:0)/Total PC 
                 0.0000001 
                 48.7385500 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:3 
                 0.0000001 
                 57.2475183 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:3 
                 0.0000002 
                 53.4975004 
               
               
                 LacCer(d18:1/20:0)/PC 18:0/20:3 
                 0.0000002 
                 56.3125345 
               
               
                 LacCer(d18:1/18:0)/PC 18:0/20:3 
                 0.0000002 
                 58.4642532 
               
               
                 Cer(d18:1/22:0)/PC 16:0/20:4 
                 0.0000002 
                 42.5755107 
               
               
                 LacCer(d18:1/20:0)/PC 18:0/18:1 
                 0.0000004 
                 50.6042672 
               
               
                 Cer(d18:1/24:1)/LPC 18:1 
                 0.0000004 
                 37.9852355 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/18:1 
                 0.0000004 
                 46.3528827 
               
               
                 LacCer(d18:1/20:0)/PC 18:1/18:1 
                 0.0000004 
                 49.6378601 
               
               
                 Cer(d18:1/18:0)/PC 16:0/18:1 
                 0.0000004 
                 42.1348344 
               
               
                 Cer(d18:1/18:0)/PC 18:0/20:4 
                 0.0000005 
                 55.4207048 
               
               
                 Cer(d18:1/24:1)/PC 18:0/20:4 
                 0.0000005 
                 40.7129933 
               
               
                 Cer(d18:1/20:0)/PC 16:0/20:3 
                 0.0000005 
                 44.8451813 
               
               
                 LacCer(d18:1/18:0)/PC 18:0/18:1 
                 0.0000006 
                 50.0860210 
               
               
                 Cer(d18:1/20:0)/PC 16:0/18:1 
                 0.0000006 
                 35.2897482 
               
               
                 LacCer(d18:1/20:0)/PC 18:1/18:2 
                 0.0000007 
                 47.4807020 
               
               
                 Cer(d18:1/24:1)/Total LPC 
                 0.0000007 
                 37.5873387 
               
               
                 Total Cer/Total PC 
                 0.0000007 
                 28.8638001 
               
               
                 Cer(d18:1/20:0)/PC 18:0/20:4 
                 0.0000007 
                 46.2204972 
               
               
                 LacCer(d18:1/18:0)/PC 18:1/18:1 
                 0.0000007 
                 47.3110220 
               
               
                 LacCer(d18:1/18:0)/PC 16:0/20:3 
                 0.0000007 
                 55.5925567 
               
               
                 LacCer(d18:1/24:1)/Total PC 
                 0.0000008 
                 56.5726916 
               
               
                 Cer(d18:1/24:1)/PC 18:0/18:1 
                 0.0000008 
                 38.3563305 
               
               
                 Cer(d18:1/24:1)/PC 18:0/20:3 
                 0.0000013 
                 39.6802706 
               
               
                 LacCer(d18:1/22:0)/PC 16:0/20:4 
                 0.0000013 
                 57.8428560 
               
               
                 LacCer(d18:1/18:0)/PC 16:0/18:1 
                 0.0000014 
                 45.2070855 
               
               
                 LacCer(d18:1/22:0)/PC 18:0/20:3 
                 0.0000014 
                 50.7183795 
               
               
                 Cer(d18:1/20:0)/PC 18:1/18:1 
                 0.0000016 
                 40.1833717 
               
               
                 LacCer(d18:1/18:0)/PC 18:1/18:2 
                 0.0000017 
                 46.5169450 
               
               
                 Cer(d18:1/22:0)/PC 16:0/20:3 
                 0.0000018 
                 33.7513783 
               
               
                 Negative correlation 
               
               
                 Cer(d18:0/22:0)/Total CE 
                 0.0000000 
                 −11.7767698 
               
               
                 Cer(d18:0/24:0)/Total CE 
                 0.0000000 
                 −18.9531828 
               
               
                 Cer(d18:0/24:1)/Total CE 
                 0.0000000 
                 −1.2444181 
               
               
                 CE 18:3/Cer(d18:1/24:1) 
                 0.0000000 
                 −35.9591235 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/24:1) 
                 0.0000004 
                 −36.1288066 
               
               
                 CE 18:3/Total Cer 
                 0.0000021 
                 −30.3105704 
               
               
                 CE 18:3/PC 16:0/16:0 
                 0.0000028 
                 −30.4716021 
               
               
                 CE 18:3/LacCer(d18:1/20:0) 
                 0.0000028 
                 −44.3063424 
               
               
                 CE 20:3/Cer(d18:1/24:1) 
                 0.0000034 
                 −28.1216690 
               
               
                 CE 18:3/PS O-16:0/18:2-alkenyl 
                 0.0000036 
                 −38.5094276 
               
               
                 CE 18:3/PS O-16:1/18:2-alkyl 
                 0.0000036 
                 −38.5094276 
               
               
                 CE 18:3/Total LacCer 
                 0.0000037 
                 −34.1308012 
               
               
                 CE 18:3/Cer(d18:1/20:0) 
                 0.0000037 
                 −33.6203392 
               
               
                 LPC 18:2/LacCer(d18:1/20:0) 
                 0.0000040 
                 −41.6604394 
               
               
                 Cer(d18:0/24:0)/Total Cer 
                 0.0000049 
                 −31.4531758 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/18:0) 
                 0.0000052 
                 −40.2960344 
               
               
                 Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl 
                 0.0000059 
                 −40.8329837 
               
               
                 Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl 
                 0.0000059 
                 −40.8329837 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/24:1) 
                 0.0000064 
                 −32.1886967 
               
               
                 Cer(d18:0/24:0)/LacCer(d18:1/24:0) 
                 0.0000067 
                 −37.0287234 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/18:0) 
                 0.0000071 
                 −36.5400374 
               
               
                 CE 14:0/Cer(d18:1/24:1) 
                 0.0000076 
                 −29.9054883 
               
               
                 CE 18:3/Cer(d18:1/16:0) 
                 0.0000079 
                 −32.5598715 
               
               
                 CE 18:3/Cer(d18:1/18:0) 
                 0.0000082 
                 −38.1543108 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/20:0) 
                 0.0000087 
                 −35.4631184 
               
               
                 CE 18:3/GlcCer(d18:1/20:0) 
                 0.0000087 
                 −36.4665498 
               
               
                 CE 18:3/Cer(d18:1/22:0) 
                 0.0000101 
                 −30.6595286 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/22:0) 
                 0.0000105 
                 −32.4086711 
               
               
                 Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl 
                 0.0000114 
                 −37.4226868 
               
               
                 Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl 
                 0.0000114 
                 −37.4226868 
               
               
                 CE 18:3/PC O-34:1 
                 0.0000122 
                 −33.4941413 
               
               
                 CE 18:3/Total CE 
                 0.0000151 
                 −20.2882080 
               
               
                 PC 16:0/20:3/PS O-16:0/18:2-alkenyl 
                 0.0000154 
                 −29.5280580 
               
               
                 PC 16:0/20:3/PS O-16:1/18:2-alkyl 
                 0.0000154 
                 −29.5280580 
               
               
                 PC 18:1/18:2/PS O-16:0/18:2-alkenyl 
                 0.0000155 
                 −23.7129392 
               
               
                 PC 18:1/18:2/PS O-16:1/18:2-alkyl 
                 0.0000155 
                 −23.7129392 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/20:0) 
                 0.0000165 
                 −31.5266149 
               
               
                 CE 18:3/LacCer(d18:1/22:0) 
                 0.0000174 
                 −37.1525849 
               
               
                 LPC 18:2/PS O-16:0/18:2-alkenyl 
                 0.0000175 
                 −30.3450779 
               
               
                 LPC 18:2/PS O-16:1/18:2-alkyl 
                 0.0000175 
                 −30.3450779 
               
               
                 CE 17:1/Cer(d18:1/24:1) 
                 0.0000186 
                 −24.8594478 
               
               
                 CE 16:0/Cer(d18:1/24:1) 
                 0.0000188 
                 −19.2509390 
               
               
                 CE 18:3/GlcCer(d18:1/18:0) 
                 0.0000221 
                 −35.5601491 
               
               
                 CE 18:3/LacCer(d18:1/18:0) 
                 0.0000326 
                 −37.4416706 
               
               
                 CE 18:3/PS O-16:0/18:1-alkenyl 
                 0.0000326 
                 −34.1672013 
               
               
                 (PS O-16:1/18:1-alkyl) 
               
               
                 CE 18:3/Cer(d18:1/24:0) 
                 0.0000331 
                 −27.4645341 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/22:0) 
                 0.0000377 
                 −28.0899033 
               
               
                 LPC 16:0/LacCer(d18:1/20:0) 
                 0.0000391 
                 −35.6188222 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/16:0) 
                 0.0000446 
                 −34.6695918 
               
               
                 Total LPC/Total LacCer 
                 0.0000469 
                 −26.0881987 
               
             
          
           
               
                 5b) Significant lipid to lipid ratios in LURIC study sorted by 
               
               
                 p-value from subjects not undergoing statin treatment 
               
             
          
           
               
                 Positive correlation 
                   
                   
               
               
                 GlcCer(d18:1/26:0)/Total CE 
                 0.000000 
                 13.329316 
               
               
                 GlcCer(d18:1/26:1)/Total CE 
                 0.000000 
                 35.356592 
               
               
                 PS O-16:0/18:2-alkenyl/Total PS O 
                 0.000000 
                 26.426208 
               
               
                 PS O-16:1/18:2-alkyl/Total PS O 
                 0.000000 
                 26.426208 
               
               
                 PS O-18:2/16:0-alkenyl/Total PS O 
                 0.000000 
                 29.590682 
               
               
                 Cer(d18:1/24:1)/Total PC 
                 0.000000 
                 43.040800 
               
               
                 Cer(d18:1/24:1)/PC 16:0/20:4 
                 0.000000 
                 59.876132 
               
               
                 Cer(d18:1/24:1)/PC 18:0/20:4 
                 0.000000 
                 46.504629 
               
               
                 Cer(d18:1/20:0)/Total PC 
                 0.000000 
                 46.216544 
               
               
                 PC 16:0/16:0/Total PC 
                 0.000000 
                 28.139641 
               
               
                 Total DAG/Total LPC 
                 0.000000 
                 57.426180 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:4 
                 0.000000 
                 73.073704 
               
               
                 Cer(d18:1/18:0)/Total PC 
                 0.000000 
                 53.769121 
               
               
                 Cer(d18:1/22:0)/Total PC 
                 0.000000 
                 34.704834 
               
               
                 Cer(d18:1/22:0)/PC 16:0/20:4 
                 0.000000 
                 47.860118 
               
               
                 Cer(d18:1/20:0)/PC 16:0/20:4 
                 0.000000 
                 64.045788 
               
               
                 LacCer(d18:1/20:0)/Total PC 
                 0.000000 
                 55.686130 
               
               
                 Cer(d18:1/18:0)/PC 18:0/20:4 
                 0.000000 
                 61.943925 
               
               
                 Cer(d18:1/20:0)/PC 18:0/20:4 
                 0.000000 
                 53.941480 
               
               
                 Cer(d18:1/24:1)/PC 16:0/18:1 
                 0.000000 
                 35.646899 
               
               
                 Cer(d18:1/24:1)/PC 16:0/20:3 
                 0.000000 
                 44.382440 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:3 
                 0.000001 
                 61.224227 
               
               
                 Cer(d18:1/20:0)/PC 16:0/20:3 
                 0.000001 
                 52.891307 
               
               
                 Cer(d18:1/24:1)/PC 18:0/18:1 
                 0.000001 
                 42.115354 
               
               
                 Cer(d18:1/22:0)/PC 18:0/20:4 
                 0.000001 
                 36.949978 
               
               
                 Cer(d18:1/20:0)/PC 18:0/18:1 
                 0.000004 
                 47.396000 
               
               
                 SM (d18:1/17:0) (d18:1/16:1-OH)/Total PC O 
                 0.000004 
                 39.660537 
               
               
                 PC O-32:0 (KDdiA-PC)/Total PC O 
                 0.000005 
                 46.418572 
               
               
                 Cer(d18:1/20:0)/PC 16:0/18:1 
                 0.000005 
                 37.704904 
               
               
                 Cer(d18:1/24:1)/LPC 18:1 
                 0.000005 
                 40.092181 
               
               
                 Cer(d18:1/24:1)/PC 18:1/18:1 
                 0.000005 
                 38.720001 
               
               
                 Cer(d18:1/18:0)/PC 16:0/18:1 
                 0.000006 
                 44.307054 
               
               
                 LacCer(d18:1/18:0)/Total PC 
                 0.000006 
                 50.539560 
               
               
                 Cer(d18:1/20:0)/PC 18:1/18:1 
                 0.000006 
                 44.664936 
               
               
                 Cer(d18:1/18:0)/PC 18:0/18:1 
                 0.000006 
                 54.563687 
               
               
                 LacCer(d18:1/20:0)/PC 18:0/20:4 
                 0.000007 
                 66.072520 
               
               
                 Cer(d18:1/24:1)/PC 18:0/20:3 
                 0.000007 
                 44.320399 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:3 
                 0.000008 
                 56.972652 
               
               
                 Cer(d18:1/22:0)/PC 16:0/20:3 
                 0.000008 
                 37.291136 
               
               
                 PC 16:0/16:0/PC 16:0/20:4 
                 0.000009 
                 42.512740 
               
               
                 PS O-16:0/18:2-alkenyl/Total PC 
                 0.000009 
                 53.059092 
               
               
                 PS O-16:1/18:2-alkyl/Total PC 
                 0.000009 
                 53.059092 
               
               
                 LacCer(d18:1/20:0)/PC 18:0/20:3 
                 0.000009 
                 55.403274 
               
               
                 Total Cer/Total PC 
                 0.000011 
                 29.949121 
               
               
                 Total LacCer/Total PC 
                 0.000012 
                 37.815865 
               
               
                 Total DAG/Total PC 
                 0.000012 
                 57.897424 
               
               
                 Cer(d18:1/18:0)/PC 18:1/18:1 
                 0.000012 
                 49.427440 
               
               
                 LacCer(d18:1/20:0)/PC 18:1/18:2 
                 0.000013 
                 48.432788 
               
               
                 Total DAG/Total PC O 
                 0.000014 
                 52.258466 
               
               
                 Cer(d18:1/24:1)/Total LPC 
                 0.000014 
                 38.684740 
               
               
                 Negative correlation 
               
               
                 Cer(d18:0/22:0)/Total CE 
                 0.000000 
                 −6.628640 
               
               
                 Cer(d18:0/24:0)/Total CE 
                 0.000000 
                 −13.307278 
               
               
                 DAG 16:0/18:1/Total DAG 
                 0.000000 
                 −17.305276 
               
               
                 CE 18:3/Cer(d18:1/24:1) 
                 0.000000 
                 −37.975733 
               
               
                 CE 16:0/Cer(d18:1/24:1) 
                 0.000001 
                 −23.257135 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/24:1) 
                 0.000003 
                 −36.760563 
               
               
                 CE 20:4/Cer(d18:1/24:1) 
                 0.000004 
                 −28.636879 
               
               
                 CE 20:3/Cer(d18:1/24:1) 
                 0.000007 
                 −30.787067 
               
               
                 CE 14:0/Cer(d18:1/24:1) 
                 0.000008 
                 −32.409429 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/24:1) 
                 0.000011 
                 −34.086320 
               
               
                 CE 20:4/Cer(d18:1/18:0) 
                 0.000017 
                 −31.313949 
               
               
                 CE 18:3/LacCer(d18:1/20:0) 
                 0.000017 
                 −45.652383 
               
               
                 CE 18:3/Cer(d18:1/20:0) 
                 0.000019 
                 −34.938575 
               
               
                 CE 17:1/Cer(d18:1/24:1) 
                 0.000020 
                 −27.626744 
               
               
                 CE 18:3/Cer(d18:1/18:0) 
                 0.000022 
                 −39.797182 
               
               
                 CE 18:3/PS O-16:0/18:2-alkenyl 
                 0.000023 
                 −40.724368 
               
               
                 CE 18:3/PS O-16:1/18:2-alkyl 
                 0.000023 
                 −40.724368 
               
               
                 CE 18:3/PC O-34:1 
                 0.000025 
                 −36.379680 
               
               
                 CE 18:3/Total DAG 
                 0.000025 
                 −40.454303 
               
               
                 CE 18:3/PC 16:0/16:0 
                 0.000026 
                 −31.169278 
               
               
                 CE 18:2/Cer(d18:1/24:1) 
                 0.000027 
                 −23.500781 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/18:0) 
                 0.000031 
                 −38.447200 
               
               
                 CE 18:3/Total Cer 
                 0.000034 
                 −30.424215 
               
               
                 Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl 
                 0.000045 
                 −37.930990 
               
               
                 Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl 
                 0.000045 
                 −37.930990 
               
               
                 LPC 18:2/LacCer(d18:1/20:0) 
                 0.000045 
                 −40.925010 
               
               
                 PC 18:0/20:4/PS O-16:0/18:2-alkenyl 
                 0.000046 
                 −31.467609 
               
               
                 PC 18:0/20:4/PS O-16:1/18:2-alkyl 
                 0.000046 
                 −31.467609 
               
               
                 PC 16:0/20:4/Total DAG 
                 0.000046 
                 −36.637600 
               
               
                 CE 16:0/Cer(d18:1/18:0) 
                 0.000047 
                 −26.423623 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/20:0) 
                 0.000051 
                 −32.923442 
               
               
                 PC 16:0/20:3/PS O-16:0/18:2-alkenyl 
                 0.000051 
                 −30.612669 
               
               
                 PC 16:0/20:3/PS O-16:1/18:2-alkyl 
                 0.000051 
                 −30.612669 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/18:0) 
                 0.000052 
                 −41.966868 
               
               
                 CE 17:1/Cer(d18:1/18:0) 
                 0.000062 
                 −30.441023 
               
               
                 CE 20:4/LacCer(d18:1/20:0) 
                 0.000062 
                 −34.937892 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/20:0) 
                 0.000077 
                 −36.424116 
               
               
                 CE 18:3/GlcCer(d18:1/20:0) 
                 0.000078 
                 −38.775015 
               
               
                 PC 16:0/20:4/PS O-16:0/18:2-alkenyl 
                 0.000079 
                 −31.649115 
               
               
                 PC 16:0/20:4/PS O-16:1/18:2-alkyl 
                 0.000079 
                 −31.649115 
               
               
                 Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl 
                 0.000082 
                 −40.069396 
               
               
                 Cer(d18:0/24:0)/PS O-16:1/18:2-alkyl 
                 0.000082 
                 −40.069396 
               
               
                 Cer(d18:0/24:0)/Total Cer 
                 0.000091 
                 −30.775984 
               
               
                 Cer(d18:0/22:0)/Total DAG 
                 0.000096 
                 −39.183597 
               
               
                 CE 18:3/Cer(d18:1/16:0) 
                 0.000101 
                 −32.942871 
               
               
                 PC 18:1/18:2/PS O-16:0/18:2-alkenyl 
                 0.000106 
                 −24.667433 
               
               
                 PC 18:1/18:2/PS O-16:1/18:2-alkyl 
                 0.000106 
                 −24.667433 
               
               
                 CE 18:3/Cer(d18:1/22:0) 
                 0.000109 
                 −30.876034 
               
               
                 CE 14:0/Cer(d18:1/18:0) 
                 0.000117 
                 −35.001327 
               
               
                 PC 18:0/20:3/PS O-16:0/18:2-alkenyl 
                 0.000119 
                 −29.825217 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
             
               
               
               
             
           
               
                 TABLE 6 
               
               
                   
               
               
                 Table of significant lipid to clinical ratios in LURIC study sorted by p-value. 
               
               
                 Lipid names and clinical measurement, p-values and percentage change both for 
               
               
                 positive and negative correlation are presented. Table 6a shows significant lipids from 
               
               
                 all study subjects. The significant lipids from subjects not undergoing statin treatment 
               
               
                 are listed in table 6b 
               
               
                   
               
             
             
               
                 6a) Significant lipid to clinical ratios in LURIC study sorted by p-value from all study 
               
               
                 subjects. 
               
             
          
           
               
                 Lipid name/clinical measurement 
                 p-value 
                 Percentage change 
               
               
                   
               
               
                 Positive correlation 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00000 
                 43.04967 
               
               
                 LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00000 
                 41.46919 
               
               
                 LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00000 
                 32.24669 
               
               
                 LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL) 
                 0.00001 
                 54.05564 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 32.96039 
               
               
                 Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL) 
                 0.00001 
                 40.06643 
               
               
                 Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00002 
                 31.56099 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 0.00002 
                 37.03057 
               
               
                 Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL) 
                 0.00003 
                 34.46408 
               
               
                 Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00003 
                 25.23403 
               
               
                 LacCer(d18:1/18:0)/triglycerides (EDTA) (mg/dL) 
                 0.00004 
                 52.60972 
               
               
                 LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL) 
                 0.00004 
                 60.79934 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein B (mg/dL) 
                 0.00004 
                 29.83861 
               
               
                 Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00004 
                 31.35691 
               
               
                 LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00005 
                 38.87517 
               
               
                 Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL) 
                 0.00005 
                 32.27486 
               
               
                 LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00006 
                 39.32664 
               
               
                 LacCer(d18:1/22:0)/triglycerides (EDTA) (mg/dL) 
                 0.00006 
                 49.54525 
               
               
                 LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL) 
                 0.00007 
                 41.61371 
               
               
                 LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL) 
                 0.00007 
                 36.35465 
               
               
                 Total LacCer/total cholesterol (EDTA) (mg/dL) 
                 0.00008 
                 23.69633 
               
               
                 Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL) 
                 0.00008 
                 37.38237 
               
               
                 Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL) 
                 0.00011 
                 21.94547 
               
               
                 Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 0.00011 
                 27.12684 
               
               
                 Cer(d18:1/18:0)/apolipoprotein B (mg/dL) 
                 0.00017 
                 27.27914 
               
               
                 LacCer(d18:1/20:0)/total-c/HDL-c 
                 0.00018 
                 33.48550 
               
               
                 LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 0.00018 
                 36.33201 
               
               
                 Total LacCer/triglycerides (EDTA) (mg/dL) 
                 0.00022 
                 38.52220 
               
               
                 LacCer(d18:1/24:1)/apolipoprotein B (mg/dL) 
                 0.00022 
                 33.98045 
               
               
                 LacCer(d18:1/18:0)/apolipoprotein B (mg/dL) 
                 0.00022 
                 33.69302 
               
               
                 LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00024 
                 29.19905 
               
               
                 Total LacCer/apolipoprotein A-I (mg/dL) 
                 0.00025 
                 25.87122 
               
               
                 PC O-32:0 (KDdiA-PC)/triglycerides (EDTA) (mg/dL) 
                 0.00029 
                 48.31010 
               
               
                 LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL) 
                 0.00031 
                 31.95659 
               
               
                 Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL) 
                 0.00037 
                 28.23304 
               
               
                 Total Cer/triglycerides (EDTA) (mg/dL) 
                 0.00043 
                 26.80115 
               
               
                 LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL) 
                 0.00050 
                 24.24011 
               
               
                 Cer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 0.00052 
                 20.79615 
               
               
                 LacCer(d18:1/22:0)/total-c/HDL-c 
                 0.00061 
                 27.84411 
               
               
                 Total LacCer/apolipoprotein B (mg/dL) 
                 0.00065 
                 20.63257 
               
               
                 PC O-34:1/triglycerides (EDTA) (mg/dL) 
                 0.00066 
                 38.80785 
               
               
                 PC O-32:0 (KDdiA-PC)/apolipoprotein A-I (mg/dL) 
                 0.00066 
                 36.57664 
               
               
                 Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00067 
                 30.67863 
               
               
                 LacCer(d18:1/18:0)/total-c/HDL-c 
                 0.00073 
                 30.67436 
               
               
                 PS O-18:2/16:0-alkenyl/HDL cholesterol (EDTA) (mg/dL) 
                 0.00073 
                 57.54661 
               
               
                 LacCer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00079 
                 38.04132 
               
               
                 Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL) 
                 0.00083 
                 28.51323 
               
               
                 Cer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00085 
                 36.16483 
               
               
                 Cer(d18:1/18:0)/total-c/HDL-c 
                 0.00087 
                 21.75165 
               
               
                 LacCer(d18:1/20:0)/apoA1/apoB 
                 0.00090 
                 32.36387 
               
               
                 Negative correlation 
               
               
                 CE 18:3/apolipoprotein B (mg/dL) 
                 0.00016 
                 −25.31907 
               
               
                 CE 18:3/total cholesterol (EDTA) (mg/dL) 
                 0.00026 
                 −23.67665 
               
               
                 CE 18:3/LDL cholesterol (EDTA) (mg/dL) 
                 0.00052 
                 −27.21759 
               
               
                 CE 18:3/apolipoprotein A-I (mg/dL) 
                 0.00054 
                 −23.09816 
               
               
                 CE 18:3/LDL-c/HDL-c 
                 0.00060 
                 −31.33346 
               
               
                 CE 18:3/apoA1/apoB 
                 0.00068 
                 −27.55825 
               
               
                 CE 18:3/total-c/HDL-c 
                 0.00070 
                 −27.28733 
               
               
                 CE 18:3/HDL cholesterol (EDTA) (mg/dL) 
                 0.00072 
                 −24.04060 
               
               
                 Cer(d18:0/24:0)/apolipoprotein B (mg/dL) 
                 0.00181 
                 −26.25271 
               
               
                 CE 14:0/LDL-c/HDL-c 
                 0.00241 
                 −27.07756 
               
               
                 Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00281 
                 −24.73116 
               
               
                 Cer(d18:0/24:0)/total-c/HDL-c 
                 0.00347 
                 −27.84469 
               
               
                 CE 14:0/total-c/HDL-c 
                 0.00356 
                 −23.22809 
               
               
                 PC 16:0/20:3/total-c/HDL-c 
                 0.00364 
                 −19.07121 
               
               
                 CE 14:0/apolipoprotein B (mg/dL) 
                 0.00375 
                 −19.76414 
               
               
                 Total PC/LDL-c/HDL-c 
                 0.00402 
                 −21.24583 
               
               
                 Cer(d18:0/24:0)/LDL-c/HDL-c 
                 0.00502 
                 −33.76759 
               
               
                 Total PC/apolipoprotein B (mg/dL) 
                 0.00513 
                 −12.91145 
               
               
                 Total PC/total-c/HDL-c 
                 0.00535 
                 −16.13350 
               
               
                 CE 20:3/LDL-c/HDL-c 
                 0.00547 
                 −21.16631 
               
               
                 PC 16:0/20:4/apolipoprotein B (mg/dL) 
                 0.00576 
                 −15.39247 
               
               
                 PC 16:0/20:4/total-c/HDL-c 
                 0.00682 
                 −18.06323 
               
               
                 Cer(d18:0/22:0)/LDL-c/HDL-c 
                 0.00748 
                 −29.05891 
               
               
                 Total PC/total cholesterol (EDTA) (mg/dL) 
                 0.00760 
                 −10.60231 
               
               
                 Cer(d18:0/22:0)/total-c/HDL-c 
                 0.00765 
                 −23.72182 
               
               
                 PC 16:0/20:3/LDL-c/HDL-c 
                 0.00784 
                 −22.56336 
               
               
                 PC 18:0/20:3/total-c/HDL-c 
                 0.00794 
                 −17.83335 
               
               
                 CE 14:0/total cholesterol (EDTA) (mg/dL) 
                 0.00816 
                 −17.44260 
               
               
                 CE 20:3/total-c/HDL-c 
                 0.00819 
                 −17.34055 
               
               
                 PC 16:0/20:4/LDL-c/HDL-c 
                 0.00828 
                 −21.49898 
               
               
                 CE 17:1/LDL-c/HDL-c 
                 0.00832 
                 −21.33179 
               
               
                 CE 14:0/LDL cholesterol (EDTA) (mg/dL) 
                 0.00832 
                 −20.55966 
               
               
                 Cer(d18:0/24:0)/LDL cholesterol (EDTA) (mg/dL) 
                 0.00848 
                 −30.08563 
               
               
                 LPC 18:2/LDL-c/HDL-c 
                 0.00873 
                 −21.70580 
               
               
                 Total LPC/LDL-c/HDL-c 
                 0.00881 
                 −20.39287 
               
               
                 PC 18:0/20:3/LDL-c/HDL-c 
                 0.00947 
                 −22.19538 
               
               
                 Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL) 
                 0.01052 
                 −22.39254 
               
               
                 Cer(d18:0/22:0)/apolipoprotein B (mg/dL) 
                 0.01094 
                 −21.02661 
               
               
                 CE 20:3/apolipoprotein B (mg/dL) 
                 0.01105 
                 −15.18746 
               
               
                 PC 16:0/20:4/total cholesterol (EDTA) (mg/dL) 
                 0.01131 
                 −13.37554 
               
               
                 Total LPC/total-c/HDL-c 
                 0.01183 
                 −16.82334 
               
               
                 LPC 18:2/apoA1/apoB 
                 0.01189 
                 −19.23316 
               
               
                 PC 16:0/20:3/apolipoprotein B (mg/dL) 
                 0.01273 
                 −15.11848 
               
               
                 CE 16:1/apolipoprotein B (mg/dL) 
                 0.01456 
                 −26.99397 
               
               
                 Cer(d18:0/24:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.01507 
                 −23.10073 
               
               
                 CE 16:1/LDL cholesterol (EDTA) (mg/dL) 
                 0.01581 
                 −29.68280 
               
               
                 PC 18:0/18:1/LDL-c/HDL-c 
                 0.01581 
                 −25.72002 
               
               
                 CE 20:5/HDL cholesterol (EDTA) (mg/dL) 
                 0.01584 
                 −23.45029 
               
               
                 CE 20:5/apolipoprotein B (mg/dL) 
                 0.01619 
                 −27.03163 
               
               
                 LPC 18:2/LDL cholesterol (EDTA) (mg/dL) 
                 0.01648 
                 −17.26480 
               
               
                   
               
             
          
           
               
                 6b) Significant lipid to clinical ratios in LURIC study sorted by p-value from subjects 
               
               
                 not undergoing statin treatment. 
               
             
          
           
               
                 Lipid name/Clinical measurement 
                 p-value 
                 Percentage change 
               
               
                   
               
               
                 Positive correlation 
               
               
                 Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00000 
                 38.78716 
               
               
                 Cer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 0.00000 
                 35.29473 
               
               
                 Cer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00000 
                 44.87416 
               
               
                 Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL) 
                 0.00000 
                 31.81230 
               
               
                 Cer(d18:1/18:0)/apolipoprotein B (mg/dL) 
                 0.00000 
                 41.46939 
               
               
                 Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00000 
                 43.22923 
               
               
                 Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 0.00000 
                 36.15491 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 47.52465 
               
               
                 Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 49.43693 
               
               
                 LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00001 
                 47.43498 
               
               
                 Cer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00001 
                 26.21569 
               
               
                 LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00001 
                 36.57029 
               
               
                 Cer(d18:1/24:1)/apolipoprotein B (mg/dL) 
                 0.00001 
                 29.03655 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 35.92744 
               
               
                 Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL) 
                 0.00002 
                 45.88769 
               
               
                 Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL) 
                 0.00002 
                 41.38147 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 0.00002 
                 43.58427 
               
               
                 Total Cer/total cholesterol (EDTA) (mg/dL) 
                 0.00002 
                 22.69184 
               
               
                 Total DAG/triglycerides (EDTA) (mg/dL) 
                 0.00003 
                 42.61436 
               
               
                 LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL) 
                 0.00003 
                 42.53680 
               
               
                 Cer(d18:1/18:0)/total-c/HDL-c 
                 0.00003 
                 32.87649 
               
               
                 Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL) 
                 0.00004 
                 37.38060 
               
               
                 Cer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00004 
                 44.64484 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein B (mg/dL) 
                 0.00004 
                 35.19942 
               
               
                 Cer(d18:1/22:0)/apolipoprotein B (mg/dL) 
                 0.00005 
                 24.23877 
               
               
                 LacCer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL) 
                 0.00006 
                 43.51653 
               
               
                 LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00006 
                 45.00931 
               
               
                 Total LacCer/total cholesterol (EDTA) (mg/dL) 
                 0.00007 
                 27.38505 
               
               
                 Cer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00008 
                 50.71310 
               
               
                 Cer(d18:1/24:1)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00008 
                 36.69128 
               
               
                 LacCer(d18:1/20:0)/triglycerides (EDTA) (mg/dL) 
                 0.00009 
                 53.20068 
               
               
                 LacCer(d18:1/24:1)/apolipoprotein B (mg/dL) 
                 0.00009 
                 42.74199 
               
               
                 Cer(d18:1/20:0)/total-c/HDL-c 
                 0.00010 
                 26.38965 
               
               
                 LacCer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL) 
                 0.00010 
                 31.99739 
               
               
                 Cer(d18:1/22:0)/apolipoprotein A-I (mg/dL) 
                 0.00011 
                 28.85911 
               
               
                 LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL) 
                 0.00013 
                 64.74061 
               
               
                 Total Cer/apolipoprotein B (mg/dL) 
                 0.00015 
                 21.06506 
               
               
                 Total Cer/apolipoprotein A-I (mg/dL) 
                 0.00016 
                 25.36811 
               
               
                 Cer(d18:1/16:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00016 
                 27.48182 
               
               
                 LacCer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 0.00017 
                 41.35186 
               
               
                 Cer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL) 
                 0.00018 
                 35.64759 
               
               
                 LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL) 
                 0.00019 
                 42.30922 
               
               
                 LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL) 
                 0.00020 
                 33.63345 
               
               
                 LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL) 
                 0.00022 
                 44.38352 
               
               
                 Cer(d18:1/18:0)/LDL cholesterol (EDTA) (mg/dL) 
                 0.00023 
                 42.34532 
               
               
                 Total LacCer/apolipoprotein A-I (mg/dL) 
                 0.00031 
                 28.05057 
               
               
                 Total LacCer/apolipoprotein B (mg/dL) 
                 0.00035 
                 24.82894 
               
               
                 Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL) 
                 0.00039 
                 32.11726 
               
               
                 LacCer(d18:1/20:0)/total-c/HDL-c 
                 0.00040 
                 37.19117 
               
               
                 Cer(d18:1/16:0)/apolipoprotein A-I (mg/dL) 
                 0.00042 
                 30.73655 
               
               
                 Negative correlation 
               
               
                 CE 18:3/apoA1/apoB 
                 0.00213 
                 −27.06449 
               
               
                 CE 18:3/apolipoprotein A-I (mg/dL) 
                 0.00385 
                 −21.63982 
               
               
                 CE 18:3/apolipoprotein B (mg/dL) 
                 0.00576 
                 −21.66212 
               
               
                 CE 18:3/total cholesterol (EDTA) (mg/dL) 
                 0.00593 
                 −20.58905 
               
               
                 CE 18:3/HDL cholesterol (EDTA) (mg/dL) 
                 0.00621 
                 −21.44255 
               
               
                 CE 18:3/total-c/HDL-c 
                 0.01166 
                 −23.94433 
               
               
                 CE 18:3/LDL-c/HDL-c 
                 0.01395 
                 −25.96634 
               
               
                 CE 18:3/LDL cholesterol (EDTA) (mg/dL) 
                 0.01410 
                 −22.13225 
               
               
                 CE 14:0/total-c/HDL-c 
                 0.02379 
                 −20.97683 
               
               
                 CE 14:0/LDL-c/HDL-c 
                 0.03038 
                 −22.86773 
               
               
                 Cer(d18:0/24:0)/apolipoprotein B (mg/dL) 
                 0.03428 
                 −21.10483 
               
               
                 CE 14:0/apolipoprotein B (mg/dL) 
                 0.03640 
                 −16.53355 
               
               
                 Cer(d18:0/24:0)/total-c/HDL-c 
                 0.04122 
                 −23.22174 
               
               
                 Cer(d18:0/24:0)/total cholesterol (EDTA) (mg/dL) 
                 0.04309 
                 −19.71324 
               
               
                 CE 14:0/apoA1/apoB 
                 0.04354 
                 −18.62921 
               
               
                 CE 16:1/apoA1/apoB 
                 0.04511 
                 −23.73367 
               
               
                   
               
             
          
         
       
     
         [0134]    The biomarker ability of measured lipids was assessed also by calculating the sensitivity and specificity values for each lipid and their ratios to other lipids or classical biomarkers such as LDL-C and apolipoproteins. This ROC curve analysis revealed a number of biomarker candidates that have equal of higher than 60% sensitivity and specificity for predicting CVD complications (Tables 7-9). 
         [0000]    
       
         
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Significant lipids in LURIC study sorted by top sensitivity and specificity. 
               
               
                 Table 7a shows significant lipids from all study subjects. The significant 
               
               
                 lipids from subjects not undergoing statin treatment are listed in table 7b. 
               
             
          
           
               
                   
                   
                   
                 Percentage 
               
               
                 Lipid name 
                 Sensitivity 
                 Specificity 
                 change 
               
               
                   
               
             
          
           
               
                 7a) Significant lipids in LURIC study sorted by top sensitivity and 
               
               
                 specificity from all study subjects. 
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
               
               
                 LacCer(d18:1/20:0) 
                 66.03774 
                 63.70370 
                 29.52421 
               
               
                 Total LacCer 
                 63.15789 
                 60.12270 
                 13.83938 
               
               
                 Cer(d18:1/24:1) 
                 61.40351 
                 60.12270 
                 14.88898 
               
               
                 Negative correlation 
               
               
                 Total PC 
                 71.92982 
                 63.29114 
                 −16.07367 
               
               
                 PC 16:0/20:3 
                 71.42857 
                 60.75949 
                 −18.78110 
               
               
                 Total LPC 
                 70.17544 
                 60.75949 
                 −17.02070 
               
               
                 PC 18:0/20:3 
                 66.03774 
                 63.05732 
                 −17.20664 
               
               
                 LPC 18:1 
                 64.91228 
                 60.12658 
                 −14.45827 
               
               
                 SM (d18:1/14:0) (d18:1/13:1-OH) 
                 63.79310 
                 60.50955 
                 −10.49341 
               
               
                 Cer(d18:0/22:0) 
                 61.40351 
                 61.34969 
                 −22.37263 
               
               
                 PC 16:0/18:2 
                 61.40351 
                 60.12658 
                 −8.30551 
               
               
                 PC 16:0/22:6 
                 60.37736 
                 61.14650 
                 −16.65050 
               
             
          
           
               
                 7b) Significant lipids in LURIC study sorted by top sensitivity and 
               
               
                 specificity from subjects not undergoing statin treatment. 
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
               
               
                 LacCer(d18:1/20:0) 
                 70.45455 
                 60.00000 
                 29.52421 
               
               
                 Cer(d18:1/24:1) 
                 69.56522 
                 60.34483 
                 14.88898 
               
               
                 Cer(d18:1/20:0) 
                 65.21739 
                 64.65517 
                 17.32385 
               
               
                 Cer(d18:1/22:0) 
                 60.86957 
                 62.93103 
                 10.65433 
               
               
                 GlcCer(d18:1/24:1) 
                 60.86957 
                 62.06897 
                 12.75066 
               
               
                 LacCer(d18:1/22:0) 
                 60.00000 
                 61.76471 
                 22.75541 
               
               
                 Negative correlation 
               
               
                 Total PC 
                 69.56522 
                 61.60714 
                 −16.07367 
               
               
                 PC 16:0/20:3 
                 64.44444 
                 60.71429 
                 −18.78110 
               
               
                 SM (d18:1/14:0) 
                 63.82979 
                 60.71429 
                 −10.49341 
               
               
                 (d18:1/13:1-OH) 
               
               
                 LPC 18:1 
                 63.04348 
                 60.71429 
                 −14.45827 
               
               
                 Total LPC 
                 63.04348 
                 60.71429 
                 −17.02070 
               
               
                 PC O-40:3 
                 60.97561 
                 60.43956 
                 −1.88354 
               
               
                 PC 16:0/20:4 
                 60.86957 
                 60.71429 
                 −18.06547 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Table of significant lipid to lipid ratios in LURIC study sorted by top 
               
               
                 sensitivity and specificity. Table 8a shows significant lipids from all study subjects. 
               
               
                 The significant lipids from subjects not undergoing statin treatment are listed in table 
               
               
                 8b. 
               
             
          
           
               
                 Lipid name/Lipid name 
                 Sensitivity 
                 Specificity 
                 Percentage change 
               
               
                   
               
             
          
           
               
                 8a) Table of significant lipid to lipid ratios in LURIC study sorted by top sensitivity 
               
               
                 and specificity from all study subjects. 
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
               
               
                 PS O-16:0/18:2-alkenyl/Total PS O 
                 98.24561 
                 63.92405 
                 26.07240 
               
               
                 PS O-16:1/18:2-alkyl/Total PS O 
                 98.24561 
                 63.92405 
                 26.07240 
               
               
                 PS O-18:2/16:0-alkenyl/Total PS O 
                 85.45455 
                 70.66667 
                 28.78267 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:3 
                 80.39216 
                 65.11628 
                 57.24752 
               
               
                 CE 18:2/CE 18:3 
                 79.31034 
                 60.37736 
                 26.34366 
               
               
                 LacCer(d18:1/20:0)/Total LPC 
                 78.84615 
                 61.24031 
                 53.68111 
               
               
                 LacCer(d18:1/20:0)/Total PC 
                 78.84615 
                 64.34109 
                 55.30769 
               
               
                 LacCer(d18:1/20:0)/PC 18:0/20:3 
                 77.08333 
                 60.15625 
                 56.31253 
               
               
                 Cer(d18:1/24:1)/LPC 18:2 
                 75.92593 
                 63.69427 
                 48.79017 
               
               
                 CE 16:0/CE 18:3 
                 75.86207 
                 60.37736 
                 25.64615 
               
               
                 LacCer(d18:1/20:0)/Total SM 
                 75.47170 
                 60.60606 
                 29.12486 
               
               
                 Cer(d18:1/16:0)/Total PC 
                 75.00000 
                 61.14650 
                 32.91697 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:4 
                 75.00000 
                 63.05732 
                 65.70609 
               
               
                 Cer(d18:1/18:0)/Total LPC 
                 75.00000 
                 61.14650 
                 45.10211 
               
               
                 Cer(d18:1/24:1)/SM (d18:1/24:0) (d18:1/23:1- 
                 75.00000 
                 62.42038 
                 36.77357 
               
               
                 OH) 
               
               
                 Cer(d18:1/24:1)/Total LPC 
                 75.00000 
                 63.05732 
                 37.58734 
               
               
                 Cer(d18:1/24:1)/Total PC 
                 75.00000 
                 60.50955 
                 38.66127 
               
               
                 LacCer(d18:1/18:0)/Total LPC 
                 75.00000 
                 60.13072 
                 55.13308 
               
               
                 LacCer(d18:1/20:0)/SM (d18:1/17:1-OH) 
                 75.00000 
                 62.60163 
                 36.30844 
               
               
                 LacCer(d18:1/20:0)/SM (d18:1/18:0) 
                 75.00000 
                 62.60163 
                 36.30844 
               
               
                 Total Cer/Total PC 
                 75.00000 
                 63.92405 
                 28.86380 
               
               
                 LacCer(d18:1/24:0)/Total LPC 
                 74.54545 
                 61.94030 
                 36.27249 
               
               
                 LacCer(d18:1/20:0)/PC 18:2/18:2 
                 74.46809 
                 60.31746 
                 47.81762 
               
               
                 PC 16:0/16:0/Total PC 
                 73.68421 
                 65.18987 
                 26.13285 
               
               
                 Cer(d18:1/22:0)/Total PC 
                 73.21429 
                 61.78344 
                 31.36049 
               
               
                 GlcCer(d18:1/20:0)/Total PC 
                 73.21429 
                 60.50955 
                 36.81380 
               
               
                 LacCer(d18:1/16:0)/Total LPC 
                 73.21429 
                 60.50955 
                 26.35547 
               
               
                 LacCer(d18:1/18:0)/Total PC 
                 73.21429 
                 61.43791 
                 53.58552 
               
               
                 LacCer(d18:1/22:0)/SM (d18:1/14:0) 
                 73.21429 
                 60.00000 
                 30.07361 
               
               
                 (d18:1/13:1-OH) 
               
               
                 Total LacCer/Total PC 
                 73.21429 
                 60.50955 
                 40.03890 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/18:1 
                 73.07692 
                 62.01550 
                 46.35288 
               
               
                 LacCer(d18:1/20:0)/PC 18:1/18:2 
                 73.07692 
                 60.46512 
                 47.48070 
               
               
                 Cer(d18:1/26:0)/PC O-40:0 
                 72.72727 
                 62.22222 
                 9.97951 
               
               
                 LacCer(d18:1/22:0)/Total LPC 
                 72.72727 
                 64.92537 
                 41.61463 
               
               
                 LacCer(d18:1/24:1)/Total LPC 
                 72.72727 
                 60.44776 
                 45.29327 
               
               
                 PC O-18:0/18:2-alkyl/PC O-36:5 
                 72.72727 
                 61.18421 
                 25.99402 
               
               
                 PC O-32:0 (KDdiA-PC)/PC O-38:5 
                 72.54902 
                 61.36364 
                 34.00112 
               
               
                 Cer(d18:1/22:0)/LPC 18:2 
                 72.22222 
                 61.78344 
                 41.72749 
               
               
                 LacCer(d18:1/22:0)/PC 16:0/20:3 
                 72.22222 
                 66.41791 
                 51.38070 
               
               
                 LacCer(d18:1/24:0)/PC 16:0/20:3 
                 72.22222 
                 61.19403 
                 39.48118 
               
               
                 Cer(d18:1/24:1)/Total CE 
                 71.92982 
                 61.39241 
                 31.32927 
               
               
                 PC 16:0/16:0/PC 16:0/20:4 
                 71.92982 
                 61.39241 
                 38.61464 
               
               
                 PC 16:0/18:2/Total PC 
                 71.92982 
                 60.75949 
                 8.88941 
               
               
                 Total LacCer/Total PC O 
                 71.92982 
                 60.24845 
                 17.49430 
               
               
                 Cer(d18:1/16:0)/LPC 18:1 
                 71.42857 
                 63.69427 
                 30.55279 
               
               
                 Cer(d18:1/18:0)/LPC 16:0 
                 71.42857 
                 61.14650 
                 40.41256 
               
               
                 Cer(d18:1/18:0)/LPC 18:1 
                 71.42857 
                 61.78344 
                 45.33865 
               
               
                 GlcCer(d18:1/20:0)/PC 16:0/20:4 
                 71.42857 
                 60.50955 
                 46.04915 
               
               
                 LacCer(d18:1/24:1)/Total PC O 
                 71.42857 
                 60.14493 
                 21.09716 
               
               
                 CE 19:1/Cer(d18:0/22:0) 
                 71.15385 
                 60.14493 
                 39.21301 
               
               
                 Negative correlation 
               
               
                 CE 18:3/LacCer(d18:1/20:0) 
                 84.90566 
                 62.87879 
                 −44.30634 
               
               
                 CE 18:3/Cer(d18:1/24:1) 
                 80.70175 
                 60.12658 
                 −35.95912 
               
               
                 Cer(d18:0/24:0)/Total Cer 
                 80.70175 
                 60.12270 
                 −31.45318 
               
               
                 LPC 18:2/LacCer(d18:1/20:0) 
                 80.00000 
                 64.34109 
                 −41.66044 
               
               
                 CE 18:3/Total CE 
                 79.31034 
                 61.00629 
                 −20.28821 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/20:0) 
                 79.16667 
                 61.40351 
                 −23.71130 
               
               
                 CE 16:1/Cer(d18:1/20:0) 
                 78.94737 
                 61.39241 
                 −33.84979 
               
               
                 CE 16:1/Cer(d18:1/24:1) 
                 77.19298 
                 61.39241 
                 −36.17234 
               
               
                 CE 16:1/LacCer(d18:1/18:0) 
                 77.19298 
                 60.38961 
                 −37.93756 
               
               
                 CE 18:3/Cer(d18:1/20:0) 
                 77.19298 
                 60.75949 
                 −33.62034 
               
               
                 LPC 18:1/LacCer(d18:1/20:0) 
                 76.92308 
                 63.56589 
                 −34.40451 
               
               
                 CE 18:3/LacCer(d18:1/22:0) 
                 76.78571 
                 61.02941 
                 −37.15258 
               
               
                 CE 16:1/CE 19:1 
                 75.47170 
                 60.86957 
                 −66.77151 
               
               
                 CE 16:1/Cer(d18:1/18:0) 
                 75.43860 
                 61.39241 
                 −39.42716 
               
               
                 CE 16:1/LacCer(d18:1/16:0) 
                 75.43860 
                 60.12658 
                 −30.53235 
               
               
                 CE 16:1/Total LacCer 
                 75.43860 
                 60.75949 
                 −34.87060 
               
               
                 CE 18:3/PC 16:0/16:0 
                 75.43860 
                 60.00000 
                 −30.47160 
               
               
                 CE 18:3/PS O-16:0/18:2-alkenyl 
                 75.43860 
                 60.64516 
                 −38.50943 
               
               
                 CE 18:3/PS O-16:1/18:2-alkyl 
                 75.43860 
                 60.64516 
                 −38.50943 
               
               
                 CE 18:3/Total LacCer 
                 75.43860 
                 63.29114 
                 −34.13080 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/22:0) 
                 75.43860 
                 66.25767 
                 −32.40867 
               
               
                 CE 16:1/LacCer(d18:1/22:0) 
                 75.00000 
                 61.02941 
                 −37.29505 
               
               
                 CE 16:1/LacCer(d18:1/24:0) 
                 75.00000 
                 60.29412 
                 −36.84318 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/22:0) 
                 75.00000 
                 60.86957 
                 −20.64622 
               
               
                 LPC 16:0/LacCer(d18:1/20:0) 
                 75.00000 
                 61.24031 
                 −35.61882 
               
               
                 Total LPC/Total LacCer 
                 75.00000 
                 61.78344 
                 −26.08820 
               
               
                 LPC 16:0/LacCer(d18:1/24:1) 
                 74.54545 
                 60.44776 
                 −24.61533 
               
               
                 CE 17:1/GlcCer(d18:1/24:1) 
                 74.07407 
                 60.25641 
                 −24.94421 
               
               
                 CE 16:1/GlcCer(d18:1/18:0) 
                 73.68421 
                 60.12658 
                 −36.48698 
               
               
                 CE 16:1/GlcCer(d18:1/20:0) 
                 73.68421 
                 60.75949 
                 −38.30453 
               
               
                 CE 16:1/PC 16:0/16:0 
                 73.68421 
                 60.64516 
                 −29.10430 
               
               
                 CE 18:1/Total LacCer 
                 73.68421 
                 60.12658 
                 −20.87773 
               
               
                 CE 18:3/Cer(d18:1/16:0) 
                 73.68421 
                 67.08861 
                 −32.55987 
               
               
                 CE 18:3/Cer(d18:1/22:0) 
                 73.68421 
                 61.39241 
                 −30.65953 
               
               
                 CE 20:3/Cer(d18:1/24:1) 
                 73.68421 
                 61.39241 
                 −28.12167 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/24:1) 
                 73.68421 
                 61.96319 
                 −32.18870 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/18:0) 
                 73.68421 
                 63.80368 
                 −40.29603 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/24:1) 
                 73.68421 
                 65.64417 
                 −36.12881 
               
               
                 Cer(d18:0/24:0)/GlcCer(d18:1/20:0) 
                 73.68421 
                 60.73620 
                 −40.34621 
               
               
                 CE 16:1/LacCer(d18:1/20:0) 
                 73.58491 
                 62.12121 
                 −39.47654 
               
               
                 CE 20:3/LacCer(d18:1/20:0) 
                 73.58491 
                 62.12121 
                 −35.94789 
               
               
                 CE 18:3/LacCer(d18:1/24:0) 
                 73.21429 
                 62.50000 
                 −35.91095 
               
               
                 CE 18:3/PS O-16:0/18:1-alkenyl (PS O- 
                 73.21429 
                 60.64516 
                 −34.16720 
               
               
                 16:1/18:1-alkyl) 
               
               
                 Cer(d18:0/22:0)/LacCer(d18:1/24:0) 
                 73.21429 
                 60.00000 
                 −31.24173 
               
               
                 Cer(d18:0/24:0)/LacCer(d18:1/24:0) 
                 73.21429 
                 62.85714 
                 −37.02872 
               
               
                 LPC 16:0/Total LacCer 
                 73.21429 
                 61.78344 
                 −24.37341 
               
               
                 SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer 
                 73.21429 
                 61.14650 
                 −13.97590 
               
               
                 Cer(d18:0/24:0)/SM (d18:1/17:0) (d18:1/16:1- 
                 72.91667 
                 60.00000 
                 −44.87505 
               
               
                 OH) 
               
               
                 LPC 16:0/LacCer(d18:1/22:0) 
                 72.72727 
                 67.16418 
                 −27.47521 
               
               
                 CE 17:1/LacCer(d18:1/18:0) 
                 72.22222 
                 60.52632 
                 −27.90709 
               
             
          
           
               
                 8b) Table of significant lipid to lipid ratios in LURIC study sorted by top sensitivity 
               
               
                 and specificity from subjects not undergoing statin treatment. 
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
               
               
                 PS O-16:0/18:2-alkenyl/Total PS O 
                 97.82609 
                 62.50000 
                 26.42621 
               
               
                 PS O-16:1/18:2-alkyl/Total PS O 
                 97.82609 
                 62.50000 
                 26.42621 
               
               
                 PS O-18:2/16:0-alkenyl/Total PS O 
                 88.63636 
                 72.64151 
                 29.59068 
               
               
                 Cer(d18:1/24:1)/LPC 18:2 
                 81.39535 
                 62.16216 
                 51.68188 
               
               
                 CE 18:2/CE 18:3 
                 80.85106 
                 60.52632 
                 24.84398 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:4 
                 80.00000 
                 62.16216 
                 73.07370 
               
               
                 Cer(d18:1/24:1)/PC 16:0/18:2 
                 80.00000 
                 60.36036 
                 27.45405 
               
               
                 Cer(d18:1/24:1)/Total LPC 
                 80.00000 
                 62.16216 
                 38.68474 
               
               
                 Cer(d18:1/24:1)/Total PC 
                 80.00000 
                 62.16216 
                 43.04080 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:4 
                 79.06977 
                 68.42105 
                 82.44735 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:3 
                 78.57143 
                 64.21053 
                 56.97265 
               
               
                 Cer(d18:1/16:0)/Total PC 
                 77.77778 
                 60.36036 
                 34.07762 
               
               
                 Cer(d18:1/18:0)/LPC 18:1 
                 77.77778 
                 60.36036 
                 45.52166 
               
               
                 Cer(d18:1/24:1)/SM (d18:1/24:0) (d18:1/23:1-OH) 
                 77.77778 
                 60.17699 
                 32.27927 
               
               
                 Cer(d18:1/24:1)/PC O-40:3 
                 77.50000 
                 60.43956 
                 20.46959 
               
               
                 LacCer(d18:1/20:0)/Total LPC 
                 76.74419 
                 60.00000 
                 49.56627 
               
               
                 LacCer(d18:1/20:0)/Total PC 
                 76.74419 
                 63.15789 
                 55.68613 
               
               
                 Cer(d18:1/18:0)/Total CE 
                 76.08696 
                 60.17699 
                 49.43112 
               
               
                 Cer(d18:1/20:0)/SM (d18:1/14:0) (d18:1/13:1-OH) 
                 76.08696 
                 60.71429 
                 28.98221 
               
               
                 Cer(d18:1/20:0)/Total PC O 
                 76.08696 
                 60.86957 
                 29.01076 
               
               
                 Cer(d18:1/24:1)/Total CE 
                 76.08696 
                 60.17699 
                 39.34990 
               
               
                 PS O-16:0/18:2-alkenyl/Total PC O 
                 76.08696 
                 61.60714 
                 20.69456 
               
               
                 PS O-16:1/18:2-alkyl/Total PC O 
                 76.08696 
                 61.60714 
                 20.69456 
               
               
                 Cer(d18:1/16:0)/LPC 18:1 
                 75.55556 
                 60.36036 
                 26.36925 
               
               
                 Cer(d18:1/18:0)/Total LPC 
                 75.55556 
                 63.06306 
                 44.40414 
               
               
                 Cer(d18:1/22:0)/Total PC 
                 75.55556 
                 63.06306 
                 34.70483 
               
               
                 Total Cer/Total PC 
                 75.55556 
                 61.60714 
                 29.94912 
               
               
                 LacCer(d18:1/20:0)/Total SM 
                 75.00000 
                 61.61616 
                 27.48798 
               
               
                 LacCer(d18:1/24:0)/Total LPC 
                 75.00000 
                 67.01031 
                 34.46432 
               
               
                 PS O-18:2/16:0-alkenyl/Total PC O 
                 75.00000 
                 60.37736 
                 21.65448 
               
               
                 CE 16:0/CE 18:3 
                 74.46809 
                 61.40351 
                 25.51627 
               
               
                 CE 18:0/CE 18:3 
                 74.46809 
                 65.13761 
                 29.77017 
               
               
                 Cer(d18:1/22:0)/LPC 18:2 
                 74.41860 
                 60.36036 
                 44.40272 
               
               
                 LacCer(d18:1/20:0)/PC 18:1/18:2 
                 74.41860 
                 64.21053 
                 48.43279 
               
               
                 LacCer(d18:1/20:0)/SM (d18:1/17:1-OH) 
                 74.41860 
                 60.86957 
                 34.96305 
               
               
                 LacCer(d18:1/20:0)/SM (d18:1/18:0) 
                 74.41860 
                 60.86957 
                 34.96305 
               
               
                 LacCer(d18:1/20:0)/PC 18:0/20:3 
                 74.35897 
                 62.76596 
                 55.40327 
               
               
                 Cer(d18:1/18:0)/SM (d18:1/14:0) (d18:1/13:1-OH) 
                 73.91304 
                 74.10714 
                 34.95249 
               
               
                 Cer(d18:1/18:0)/SM (d18:1/17:2-OH) 
                 73.91304 
                 60.00000 
                 25.13954 
               
               
                 Cer(d18:1/18:0)/SM (d18:1/18:1) 
                 73.91304 
                 60.00000 
                 25.13954 
               
               
                 Cer(d18:1/24:1)/SM (d18:1/23:0) (d18:1/22:1-OH) 
                 73.91304 
                 60.71429 
                 29.95139 
               
               
                 PC 16:0/16:0/PC 16:0/20:4 
                 73.91304 
                 60.71429 
                 42.51274 
               
               
                 Cer(d18:1/20:0)/Total LPC 
                 73.33333 
                 61.26126 
                 36.63159 
               
               
                 Cer(d18:1/24:1)/PC 16:0/20:4 
                 73.33333 
                 62.16216 
                 59.87613 
               
               
                 Cer(d18:1/24:1)/PC 18:0/18:2 
                 73.33333 
                 62.16216 
                 29.37710 
               
               
                 Cer(d18:1/24:1)/PC 18:1/18:2 
                 73.33333 
                 61.26126 
                 36.88389 
               
               
                 Cer(d18:1/24:1)/SM (d18:1/17:1-OH) 
                 73.33333 
                 64.42308 
                 23.41916 
               
               
                 Cer(d18:1/24:1)/SM (d18:1/18:0) 
                 73.33333 
                 64.42308 
                 23.41916 
               
               
                 LacCer(d18:1/20:0)/PC 18:0/18:1 
                 73.17073 
                 62.10526 
                 50.18761 
               
               
                 LacCer(d18:1/20:0)/Total CE 
                 72.72727 
                 62.62626 
                 53.71776 
               
               
                 Negative correlation 
               
               
                 DAG 16:0/18:1/Total DAG 
                 88.88889 
                 61.16505 
                 −17.30528 
               
               
                 CE 18:3/LacCer(d18:1/20:0) 
                 86.36364 
                 66.66667 
                 −45.65238 
               
               
                 LPC 18:2/LacCer(d18:1/20:0) 
                 82.92683 
                 62.10526 
                 −40.92501 
               
               
                 CE 18:3/Cer(d18:1/24:1) 
                 82.60870 
                 61.06195 
                 −37.97573 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/20:0) 
                 80.48780 
                 64.77273 
                 −26.83109 
               
               
                 CE 14:0/Total DAG 
                 80.00000 
                 61.16505 
                 −39.38279 
               
               
                 CE 18:3/Total CE 
                 78.72340 
                 62.28070 
                 −19.58872 
               
               
                 PC 18:0/20:3/PS O-16:0/18:2-alkenyl 
                 78.57143 
                 60.36036 
                 −29.82522 
               
               
                 PC 18:0/20:3/PS O-16:1/18:2-alkyl 
                 78.57143 
                 60.36036 
                 −29.82522 
               
               
                 CE 16:1/Cer(d18:1/24:1) 
                 78.26087 
                 61.06195 
                 −37.53854 
               
               
                 CE 18:3/PS O-16:0/18:2-alkenyl 
                 78.26087 
                 60.90909 
                 −40.72437 
               
               
                 CE 18:3/PS O-16:1/18:2-alkyl 
                 78.26087 
                 60.90909 
                 −40.72437 
               
               
                 CE 18:3/Total LacCer 
                 78.26087 
                 60.17699 
                 −32.64187 
               
               
                 Cer(d18:0/24:0)/Total Cer 
                 78.26087 
                 62.06897 
                 −30.77598 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/22:0) 
                 78.04878 
                 61.79775 
                 −21.27116 
               
               
                 CE 18:3/LacCer(d18:1/22:0) 
                 77.77778 
                 63.63636 
                 −34.76187 
               
               
                 CE 20:3/LacCer(d18:1/20:0) 
                 77.27273 
                 60.60606 
                 −36.58675 
               
               
                 PC O-40:3/PS O-18:2/16:0-alkenyl 
                 76.92308 
                 62.79070 
                 −28.59638 
               
               
                 LPC 18:1/LacCer(d18:1/20:0) 
                 76.74419 
                 60.00000 
                 −33.84809 
               
               
                 CE 16:0/Cer(d18:1/24:1) 
                 76.08696 
                 61.06195 
                 −23.25713 
               
               
                 CE 16:1/Cer(d18:1/18:0) 
                 76.08696 
                 63.71681 
                 −41.11023 
               
               
                 CE 16:1/Cer(d18:1/20:0) 
                 76.08696 
                 66.37168 
                 −34.98271 
               
               
                 CE 16:1/GlcCer(d18:1/24:1) 
                 76.08696 
                 60.17699 
                 −39.81218 
               
               
                 CE 16:1/LacCer(d18:1/18:0) 
                 76.08696 
                 60.36036 
                 −37.28535 
               
               
                 CE 18:3/Cer(d18:1/20:0) 
                 76.08696 
                 63.71681 
                 −34.93858 
               
               
                 CE 18:3/Cer(d18:1/22:0) 
                 76.08696 
                 61.94690 
                 −30.87603 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/24:1) 
                 76.08696 
                 61.20690 
                 −34.08632 
               
               
                 Cer(d18:0/22:0)/Total GlcCer 
                 76.08696 
                 60.34483 
                 −28.95910 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/20:0) 
                 76.08696 
                 60.34483 
                 −36.42412 
               
               
                 PC 18:0/20:3/PS O-18:2/16:0-alkenyl 
                 75.60976 
                 60.95238 
                 −29.83126 
               
               
                 CE 16:1/LacCer(d18:1/24:0) 
                 75.55556 
                 60.60606 
                 −36.83943 
               
               
                 CE 18:3/LacCer(d18:1/24:0) 
                 75.55556 
                 60.60606 
                 −37.84417 
               
               
                 PC 18:1/18:2/Total Cer 
                 75.55556 
                 60.71429 
                 −19.58862 
               
               
                 SM (d18:1/23:0) (d18:1/22:1-OH)/Total DAG 
                 75.55556 
                 63.10680 
                 −37.45206 
               
               
                 SM (d18:1/24:0) (d18:1/23:1-OH)/Total Cer 
                 75.55556 
                 61.94690 
                 −11.07113 
               
               
                 Total CE/Total DAG 
                 75.55556 
                 66.01942 
                 −31.35698 
               
               
                 Total LPC/Total LacCer 
                 75.55556 
                 69.36937 
                 −23.44706 
               
               
                 CE 16:1/CE 19:1 
                 75.00000 
                 60.82474 
                 −56.18741 
               
               
                 CE 20:5/LacCer(d18:1/20:0) 
                 75.00000 
                 61.61616 
                 −37.54401 
               
               
                 LPC 16:0/LacCer(d18:1/24:0) 
                 75.00000 
                 60.82474 
                 −25.29458 
               
               
                 CE 15:0/Cer(d18:1/20:0) 
                 74.41860 
                 60.57692 
                 −21.94830 
               
               
                 CE 16:0/Cer(d18:1/18:0) 
                 73.91304 
                 61.06195 
                 −26.42362 
               
               
                 CE 16:1/Total LacCer 
                 73.91304 
                 63.71681 
                 −33.50629 
               
               
                 CE 18:2/Cer(d18:1/20:0) 
                 73.91304 
                 61.94690 
                 −19.85408 
               
               
                 CE 18:3/Cer(d18:1/24:0) 
                 73.91304 
                 61.40351 
                 −28.00256 
               
               
                 CE 18:3/GlcCer(d18:1/20:0) 
                 73.91304 
                 65.48673 
                 −38.77502 
               
               
                 CE 18:3/PC 16:0/16:0 
                 73.91304 
                 63.63636 
                 −31.16928 
               
               
                 CE 20:3/Cer(d18:1/24:1) 
                 73.91304 
                 61.06195 
                 −30.78707 
               
               
                 CE 20:4/GlcCer(d18:1/20:0) 
                 73.91304 
                 62.83186 
                 −30.95570 
               
               
                 CE 20:4/GlcCer(d18:1/24:1) 
                 73.91304 
                 61.06195 
                 −28.82844 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 Table of significant lipid to clinical ratios in LURIC study sorted by top 
               
               
                 sensitivity and specificity. Table 9a shows significant lipids from all study subjects. 
               
               
                 The significant lipids from subjects not undergoing statin treatment are listed in table 
               
               
                 9b. 
               
             
          
           
               
                   
                   
                   
                 Percentage 
               
               
                 Lipid name/Clinical measurement 
                 Sensitivity 
                 Specificity 
                 change 
               
               
                   
               
             
          
           
               
                 9a) Table of significant lipid to clinical ratios in LURIC study sorted by top sensitivity 
               
               
                 and specificity from all study subjects. 
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
               
               
                 LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 75.47170 
                 61.48148 
                 43.04967 
               
               
                 Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL) 
                 70.17544 
                 60.73620 
                 21.94547 
               
               
                 Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL) 
                 70.17544 
                 60.12270 
                 32.27486 
               
               
                 LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) 
                 69.81132 
                 62.22222 
                 39.32664 
               
               
                 LacCer(d18:1/20:0)/apoA1/apoB 
                 67.92453 
                 61.48148 
                 32.36387 
               
               
                 LacCer(d18:1/22:0)/HDL cholesterol (EDTA) (mg/dL) 
                 67.85714 
                 60.00000 
                 29.19905 
               
               
                 Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL) 
                 66.66667 
                 61.34969 
                 28.51323 
               
               
                 Cer(d18:1/22:0)/apolipoprotein B (mg/dL) 
                 66.66667 
                 60.12270 
                 14.20773 
               
               
                 Cer(d18:1/24:1)/apolipoprotein B (mg/dL) 
                 66.66667 
                 62.57669 
                 18.05222 
               
               
                 Total Cer/total cholesterol (EDTA) (mg/dL) 
                 66.66667 
                 65.85366 
                 15.12131 
               
               
                 LacCer(d18:1/20:0)/LDL-c/HDL-c 
                 66.03774 
                 60.74074 
                 23.54484 
               
               
                 LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 66.03774 
                 62.96296 
                 41.46919 
               
               
                 LacCer(d18:1/20:0)/total-c/HDL-c 
                 66.03774 
                 60.00000 
                 33.48550 
               
               
                 Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL) 
                 64.91228 
                 60.73620 
                 40.06643 
               
               
                 Cer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL) 
                 64.91228 
                 61.34969 
                 17.20335 
               
               
                 Cer(d18:1/24:1)/total-c/HDL-c 
                 64.91228 
                 61.34969 
                 13.34657 
               
               
                 GlcCer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL) 
                 64.91228 
                 61.96319 
                 17.04608 
               
               
                 LacCer(d18:1/18:0)/apolipoprotein A-I (mg/dL) 
                 64.91228 
                 60.37736 
                 41.61371 
               
               
                 LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL) 
                 64.91228 
                 61.00629 
                 38.87517 
               
               
                 Total LacCer/total cholesterol (EDTA) (mg/dL) 
                 64.91228 
                 65.03067 
                 23.69633 
               
               
                 LacCer(d18:1/22:0)/apoA1/apoB 
                 64.28571 
                 62.85714 
                 24.17423 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL) 
                 64.28571 
                 62.85714 
                 32.96039 
               
               
                 LacCer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL) 
                 64.28571 
                 60.00000 
                 32.24669 
               
               
                 LacCer(d18:1/24:0)/apoA1/apoB 
                 64.28571 
                 62.14286 
                 15.23336 
               
               
                 LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL) 
                 64.15094 
                 61.48148 
                 31.95659 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 64.15094 
                 60.00000 
                 37.03057 
               
               
                 PS O-18:2/16:0-alkenyl/triglycerides (EDTA) (mg/dL) 
                 63.63636 
                 63.33333 
                 99.88127 
               
               
                 Cer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 63.15789 
                 60.12270 
                 20.79615 
               
               
                 Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 63.15789 
                 61.96319 
                 25.23403 
               
               
                 Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL) 
                 63.15789 
                 60.12270 
                 11.30545 
               
               
                 Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL) 
                 63.15789 
                 60.12270 
                 14.20759 
               
               
                 PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL) 
                 63.15789 
                 63.29114 
                 97.78843 
               
               
                 PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL) 
                 63.15789 
                 63.29114 
                 97.78843 
               
               
                 Total GlcCer/total cholesterol (EDTA) (mg/dL) 
                 63.15789 
                 60.73620 
                 17.56924 
               
               
                 Total LacCer/apolipoprotein A-I (mg/dL) 
                 63.15789 
                 61.34969 
                 25.87122 
               
               
                 Total LacCer/apolipoprotein B (mg/dL) 
                 63.15789 
                 61.96319 
                 20.63257 
               
               
                 LacCer(d18:1/24:1)/triglycerides (EDTA) (mg/dL) 
                 62.50000 
                 62.14286 
                 60.79934 
               
               
                 PS O-16:0/18:1-alkenyl (PS O-16:1/18:1- 
                 62.50000 
                 61.39241 
                 65.88734 
               
               
                 alkyl)/triglycerides (EDTA) (mg/dL) 
               
               
                 Cer(d18:1/20:0)/triglycerides (EDTA) (mg/dL) 
                 61.40351 
                 60.73620 
                 34.46408 
               
               
                 Cer(d18:1/22:0)/triglycerides (EDTA) (mg/dL) 
                 61.40351 
                 63.19018 
                 28.23304 
               
               
                 Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 61.40351 
                 65.03067 
                 27.12684 
               
               
                 LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL) 
                 61.40351 
                 64.41718 
                 25.01312 
               
               
                 LacCer(d18:1/18:0)/HDL cholesterol (EDTA) (mg/dL) 
                 61.40351 
                 60.37736 
                 38.04132 
               
               
                 LacCer(d18:1/18:0)/LDL cholesterol (EDTA) (mg/dL) 
                 61.40351 
                 64.15094 
                 28.50180 
               
               
                 LacCer(d18:1/18:0)/apolipoprotein B (mg/dL) 
                 61.40351 
                 61.00629 
                 33.69302 
               
               
                 LacCer(d18:1/18:0)/triglycerides (EDTA) (mg/dL) 
                 61.40351 
                 62.26415 
                 52.60972 
               
               
                 Total Cer/apolipoprotein A-I (mg/dL) 
                 61.40351 
                 63.41463 
                 19.09944 
               
               
                 Total GlcCer/apolipoprotein B (mg/dL) 
                 61.40351 
                 60.12270 
                 14.92180 
               
               
                 Total LacCer/triglycerides (EDTA) (mg/dL) 
                 61.40351 
                 62.57669 
                 38.52220 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein B (mg/dL) 
                 60.71429 
                 65.00000 
                 29.83861 
               
               
                 Negative correlation 
               
               
                 CE 18:3/total-c/HDL-c 
                 67.24138 
                 62.89308 
                 −27.28733 
               
               
                 LPC 18:2/apolipoprotein B (mg/dL) 
                 65.45455 
                 60.12658 
                 −16.19596 
               
               
                 Total PC/apolipoprotein B (mg/dL) 
                 64.91228 
                 61.39241 
                 −12.91145 
               
               
                 Total PC/total cholesterol (EDTA) (mg/dL) 
                 64.91228 
                 60.75949 
                 −10.60231 
               
               
                 CE 16:1/HDL cholesterol (EDTA) (mg/dL) 
                 63.79310 
                 61.63522 
                 −22.01197 
               
               
                 CE 18:3/HDL cholesterol (EDTA) (mg/dL) 
                 63.79310 
                 62.26415 
                 −24.04060 
               
               
                 CE 18:3/LDL cholesterol (EDTA) (mg/dL) 
                 63.79310 
                 62.26415 
                 −27.21759 
               
               
                 LPC 18:2/LDL-c/HDL-c 
                 63.63636 
                 61.39241 
                 −21.70580 
               
               
                 Total PC/total-c/HDL-c 
                 63.15789 
                 60.12658 
                 −16.13350 
               
               
                 PC 16:0/20:3/HDL cholesterol (EDTA) (mg/dL) 
                 62.50000 
                 62.65823 
                 −11.45558 
               
               
                 PC 16:0/20:3/apolipoprotein B (mg/dL) 
                 62.50000 
                 60.12658 
                 −15.11848 
               
               
                 CE 16:1/apolipoprotein B (mg/dL) 
                 62.06897 
                 62.26415 
                 −26.99397 
               
               
                 CE 16:1/total cholesterol (EDTA) (mg/dL) 
                 62.06897 
                 60.37736 
                 −24.28770 
               
               
                 CE 18:3/LDL-c/HDL-c 
                 62.06897 
                 62.89308 
                 −31.33346 
               
               
                 CE 18:3/apolipoprotein A-I (mg/dL) 
                 62.06897 
                 60.37736 
                 −23.09816 
               
               
                 LPC 18:2/HDL cholesterol (EDTA) (mg/dL) 
                 61.81818 
                 60.75949 
                 −16.07209 
               
               
                 LPC 18:2/apoA1/apoB 
                 61.81818 
                 63.92405 
                 −19.23316 
               
               
                 PC 16:0/20:4/LDL cholesterol (EDTA) (mg/dL) 
                 61.40351 
                 60.12658 
                 −15.98292 
               
               
                 PC 16:0/20:4/apolipoprotein A-I (mg/dL) 
                 61.40351 
                 60.75949 
                 −12.23661 
               
               
                 PC 16:0/20:4/total cholesterol (EDTA) (mg/dL) 
                 61.40351 
                 61.39241 
                 −13.37554 
               
               
                 Total PC/LDL-c/HDL-c 
                 61.40351 
                 62.65823 
                 −21.24583 
               
               
                 PC 16:0/20:3/total-c/HDL-c 
                 60.71429 
                 61.39241 
                 −19.07121 
               
               
                 PC 18:0/20:4/apoA1/apoB 
                 60.71429 
                 62.02532 
                 −13.36540 
               
               
                 CE 18:3/apoA1/apoB 
                 60.34483 
                 60.37736 
                 −27.55825 
               
               
                 CE 18:3/apolipoprotein B (mg/dL) 
                 60.34483 
                 61.00629 
                 −25.31907 
               
               
                 CE 20:5/HDL cholesterol (EDTA) (mg/dL) 
                 60.34483 
                 60.37736 
                 −23.45029 
               
               
                 CE 20:5/LDL cholesterol (EDTA) (mg/dL) 
                 60.34483 
                 60.37736 
                 −25.93288 
               
               
                 LPC 18:2/LDL cholesterol (EDTA) (mg/dL) 
                 60.00000 
                 62.02532 
                 −17.26480 
               
               
                 LPC 18:2/total cholesterol (EDTA) (mg/dL) 
                 60.00000 
                 62.65823 
                 −14.92954 
               
             
          
           
               
                 9b) Table of significant lipid to clinical ratios in LURIC study sorted by top sensitivity 
               
               
                 and specificity from subjects not undergoing statin treatment. 
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
               
               
                 Cer(d18:1/24:1)/apolipoprotein B (mg/dL) 
                 82.60870 
                 62.06897 
                 18.05222 
               
               
                 Cer(d18:1/24:1)/total cholesterol (EDTA) (mg/dL) 
                 80.43478 
                 61.20690 
                 21.94547 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 77.27273 
                 67.00000 
                 43.04967 
               
               
                 Cer(d18:1/22:0)/LDL cholesterol (EDTA) (mg/dL) 
                 73.91304 
                 60.34483 
                 11.30545 
               
               
                 Total Cer/LDL cholesterol (EDTA) (mg/dL) 
                 73.91304 
                 62.39316 
                 8.25598 
               
               
                 Total Cer/total cholesterol (EDTA) (mg/dL) 
                 73.91304 
                 70.08547 
                 15.12131 
               
               
                 LacCer(d18:1/20:0)/HDL cholesterol (EDTA) (mg/dL) 
                 72.72727 
                 61.00000 
                 39.32664 
               
               
                 LacCer(d18:1/20:0)/apoA1/apoB 
                 72.72727 
                 60.00000 
                 32.36387 
               
               
                 Cer(d18:1/22:0)/total cholesterol (EDTA) (mg/dL) 
                 71.73913 
                 61.20690 
                 17.20335 
               
               
                 Cer(d18:1/24:1)/LDL cholesterol (EDTA) (mg/dL) 
                 71.73913 
                 61.20690 
                 14.20759 
               
               
                 Cer(d18:1/24:1)/total-c/HDL-c 
                 71.73913 
                 60.34483 
                 13.34657 
               
               
                 Total Cer/apolipoprotein A-I (mg/dL) 
                 71.73913 
                 61.53846 
                 19.09944 
               
               
                 Total Cer/apolipoprotein B (mg/dL) 
                 71.73913 
                 61.53846 
                 12.34421 
               
               
                 LacCer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL) 
                 70.45455 
                 61.00000 
                 31.95659 
               
               
                 LacCer(d18:1/20:0)/LDL-c/HDL-c 
                 70.45455 
                 61.00000 
                 23.54484 
               
               
                 Cer(d18:1/20:0)/LDL cholesterol (EDTA) (mg/dL) 
                 69.56522 
                 60.34483 
                 18.51094 
               
               
                 Cer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 69.56522 
                 68.10345 
                 20.79615 
               
               
                 Cer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 69.56522 
                 71.55172 
                 25.23403 
               
               
                 Cer(d18:1/20:0)/total-c/HDL-c 
                 69.56522 
                 60.34483 
                 14.96816 
               
               
                 Cer(d18:1/22:0)/apolipoprotein B (mg/dL) 
                 69.56522 
                 65.51724 
                 14.20773 
               
               
                 Cer(d18:1/24:0)/total cholesterol (EDTA) (mg/dL) 
                 69.56522 
                 60.68376 
                 11.30123 
               
               
                 Cer(d18:1/24:1)/LDL-c/HDL-c 
                 69.56522 
                 62.93103 
                 5.34922 
               
               
                 Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 69.56522 
                 60.34483 
                 27.12684 
               
               
                 Cer(d18:1/24:1)/triglycerides (EDTA) (mg/dL) 
                 69.56522 
                 63.79310 
                 32.27486 
               
               
                 GlcCer(d18:1/24:1)/apolipoprotein B (mg/dL) 
                 69.56522 
                 61.20690 
                 17.03707 
               
               
                 Total DAG/apolipoprotein A-I (mg/dL) 
                 68.88889 
                 60.19417 
                 15.46034 
               
               
                 LacCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 68.18182 
                 61.00000 
                 41.46919 
               
               
                 PC O-34:1/apolipoprotein B (mg/dL) 
                 68.18182 
                 60.00000 
                 22.73127 
               
               
                 Cer(d18:1/16:0)/LDL cholesterol (EDTA) (mg/dL) 
                 67.39130 
                 62.06897 
                 10.42412 
               
               
                 Cer(d18:1/18:0)/total-c/HDL-c 
                 67.39130 
                 61.20690 
                 21.75165 
               
               
                 Cer(d18:1/18:0)/triglycerides (EDTA) (mg/dL) 
                 67.39130 
                 64.65517 
                 40.06643 
               
               
                 Cer(d18:1/24:0)/LDL cholesterol (EDTA) (mg/dL) 
                 67.39130 
                 62.39316 
                 4.69599 
               
               
                 Cer(d18:1/24:0)/apolipoprotein A-I (mg/dL) 
                 67.39130 
                 61.53846 
                 14.67208 
               
               
                 GlcCer(d18:1/20:0)/total cholesterol (EDTA) (mg/dL) 
                 67.39130 
                 60.34483 
                 20.60005 
               
               
                 Total GlcCer/apolipoprotein B (mg/dL) 
                 67.39130 
                 60.34483 
                 14.92180 
               
               
                 Total LacCer/total cholesterol (EDTA) (mg/dL) 
                 67.39130 
                 62.93103 
                 23.69633 
               
               
                 LacCer(d18:1/22:0)/apoA1/apoB 
                 66.66667 
                 61.76471 
                 24.17423 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL) 
                 66.66667 
                 60.78431 
                 32.96039 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 65.90909 
                 61.00000 
                 37.03057 
               
               
                 LacCer(d18:1/20:0)/total-c/HDL-c 
                 65.90909 
                 62.00000 
                 33.48550 
               
               
                 Cer(d18:1/16:0)/triglycerides (EDTA) (mg/dL) 
                 65.21739 
                 62.06897 
                 28.51323 
               
               
                 Cer(d18:1/22:0)/apolipoprotein A-I (mg/dL) 
                 65.21739 
                 66.37931 
                 21.04730 
               
               
                 Cer(d18:1/24:0)/apolipoprotein B (mg/dL) 
                 65.21739 
                 62.39316 
                 9.26738 
               
               
                 GlcCer(d18:1/20:0)/apolipoprotein B (mg/dL) 
                 65.21739 
                 60.34483 
                 17.00627 
               
               
                 GlcCer(d18:1/26:1)/apolipoprotein A-I (mg/dL) 
                 65.21739 
                 61.60714 
                 21.90520 
               
               
                 LacCer(d18:1/16:0)/triglycerides (EDTA) (mg/dL) 
                 65.21739 
                 60.34483 
                 25.01312 
               
               
                 LacCer(d18:1/18:0)/apolipoprotein B (mg/dL) 
                 65.21739 
                 61.40351 
                 33.69302 
               
               
                 LacCer(d18:1/18:0)/total cholesterol (EDTA) (mg/dL) 
                 65.21739 
                 62.28070 
                 38.87517 
               
               
                 PS O-16:0/18:2-alkenyl/triglycerides (EDTA) (mg/dL) 
                 65.21739 
                 61.60714 
                 97.78843 
               
               
                 PS O-16:1/18:2-alkyl/triglycerides (EDTA) (mg/dL) 
                 65.21739 
                 61.60714 
                 97.78843 
               
               
                 Negative correlation 
               
               
                 CE 18:3/total-c/HDL-c 
                 68.08511 
                 62.28070 
                 −27.28733 
               
               
                 CE 18:3/LDL-c/HDL-c 
                 63.82979 
                 60.52632 
                 −31.33346 
               
               
                 CE 18:3/apoA1/apoB 
                 61.70213 
                 64.03509 
                 −27.55825 
               
               
                 CE 20:5/triglycerides (EDTA) (mg/dL) 
                 61.70213 
                 60.52632 
                 −15.26342 
               
               
                 PC O-38:6/apolipoprotein A-I (mg/dL) 
                 60.86957 
                 62.03704 
                 −3.87776 
               
               
                 Total LPC/apoA1/apoB 
                 60.86957 
                 60.71429 
                 −14.81039 
               
               
                 Total PC/apolipoprotein A-I (mg/dL) 
                 60.86957 
                 62.50000 
                 −8.50761 
               
               
                 PC 18:0/20:4/apoA1/apoB 
                 60.00000 
                 64.28571 
                 −13.36540 
               
               
                   
               
             
          
         
       
     
         [0135]    The preferred lipid molecules of the invention were selected as follows: a) it was likely to be biologically meaningful, b) it preferably belongs to a family of lipids that are behaving similarly, c) it is expressed in meaningful &amp; measurable concentrations, d) it has very significant p-value or good AUC-value (&gt;0.65) and for most also the %-change is substantial (&gt;20%), and e) it appeared significant in different tests. About 15 lipids or lipid ratios, each with either a positive or negative CVD correlation, were selected based on the highest p-values and best sensitivity and specificity subjectively ensuring the balanced representation of all lipid classes. Sensitivity and specificity thresholds were annotated in cases where the threshold of 60 and 70 were reached, respectively. The preferred embodiment lipids, lipid-lipid ratios and lipid-clinical ratios are presented in tables 10-13. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                 The preferred embodiment lipids selected from significant lipids detected 
               
               
                 from LURIC sample set. 
               
             
          
           
               
                   
                   
                 Percentage 
                   
                   
               
               
                 Lipid name 
                 p-value 
                 change 
                 Sensitivity 
                 Specificity 
               
               
                   
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
                   
               
               
                 Cer(d18:1/20:0) 
                 0.00004 
                 28.00357 
               
               
                 LacCer(d18:1/20:0) 
                 0.00010 
                 32.91154 
                 70.45455 
                 60.00000 
               
               
                 Cer(d18:1/24:1) 
                 0.00039 
                 23.37606 
                 69.56522 
                 60.34483 
               
               
                 LacCer(d18:1/24:1) 
                 0.00199 
                 29.83279 
               
               
                 PS O-18:2/16:0-alkenyl 
                 0.00432 
                 33.81177 
               
               
                 PS O-16:1/18:2-alkyl 
                 0.00590 
                 32.17190 
               
               
                 Total Cer 
                 0.00932 
                 15.44601 
               
               
                 Total LacCer 
                 0.01105 
                 16.00541 
               
               
                 GlcCer(d18:1/24:1) 
                   
                 12.75066 
                 60.86957 
                 62.06897 
               
               
                 LacCer(d18:1/22:0) 
                 0.00046 
                 22.75541 
               
               
                 Cer(d18:1/18:0) 
                 0.00009 
                 34.32550 
               
               
                 Negative correlation 
               
               
                 Total PC 
                 0.00921 
                 −12.44220 
               
               
                 PC 16:0/20:4 
                 0.02256 
                 −14.96966 
               
               
                 Cer(d18:0/24:0) 
                 0.03376 
                 −21.87004 
               
               
                 Total LPC 
                 0.03443 
                 −12.91576 
               
               
                 CE 14:0 
                 0.01090 
                 −21.01258 
               
               
                 CE 20:3 
                 0.02157 
                 −16.03606 
               
               
                 CE 17:1 
                 0.02204 
                 −15.93952 
               
               
                 PC 16:0/20:3 
                   
                 −18.78110 
                 64.44444 
                 60.71429 
               
               
                 LPC 18:1 
                   
                 −14.45827 
                 63.04348 
                 60.71429 
               
               
                 PC 18:0/20:3 
                 0.00726 
                 −17.20664 
               
               
                 PC 18:0/18:1 
                 0.00765 
                 −18.18002 
               
               
                 Cer(d18:0/22:0) 
                 0.01158 
                 −22.37263 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 11 
               
             
             
               
                   
               
               
                 Preferred embodiments from significant lipid to lipid ratios detected from LURIC 
               
               
                 sample set. 
               
             
          
           
               
                 Lipid name/Lipid name 
                 p-value 
                 Percentage change 
                 Sensitivity 
                 Specificity 
               
               
                   
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
                   
               
               
                 GlcCer(d18:1/26:1)/Total CE 
                 0.000000 
                 35.356592 
               
               
                 Cer(d18:1/24:1)/Total PC 
                 0.000000 
                 43.040800 
               
               
                 Cer(d18:1/24:1)/PC 16:0/20:4 
                 0.000000 
                 59.876132 
               
               
                 Cer(d18:1/20:0)/PC 16:0/20:4 
                 0.000000 
                 64.045788 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:3 
                 0.000008 
                 56.972652 
                 80.39216 
                 65.11628 
               
               
                 Total Cer/Total PC 
                 0.000011 
                 29.949121 
               
               
                 Total LacCer/Total PC 
                 0.000012 
                 37.815865 
               
               
                 LacCer(d18:1/20:0)/PC 18:1/18:2 
                 0.000013 
                 48.432788 
               
               
                 PS O-16:0/18:2-alkenyl/Total PS O 
                   
                 26.42621 
                 97.82609 
                 62.50000 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:4 
                   
                 73.07370 
                 80.00000 
                 62.16216 
               
               
                 LacCer(d18:1/20:0)/Total LPC 
                   
                 53.68111 
                 78.84615 
                 61.24031 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:4 
                   
                 82.44735 
                 79.06977 
                 68.42105 
               
               
                 Negative correlation 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/24:1) 
                 0.000003 
                 −36.760563 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/24:1) 
                 0.000011 
                 −34.086320 
               
               
                 DAG 16:0/18:1/Total DAG 
                   
                 −17.30528 
                 88.88889 
                 61.16505 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/22:0) 
                   
                 −32.40867 
                 75.43860 
                 66.25767 
               
               
                 Cer(d18:0/24:0)/Total CE 
                 0.0000000 
                 −18.9531828 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/24:1) 
                 0.000003 
                 −36.760563 
               
               
                 Cer(d18:0/24:0)/Total Cer 
                 0.0000049 
                 −31.4531758 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/18:0) 
                 0.0000052 
                 −40.2960344 
               
               
                 Cer(d18:0/24:0)/PS O-16:0/18:2- 
                 0.0000059 
                 −40.8329837 
               
               
                 alkenyl 
               
               
                 Cer(d18:0/24:0)/LacCer(d18:1/24:0) 
                 0.0000067 
                 −37.0287234 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/18:0) 
                 0.0000071 
                 −36.5400374 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/22:0) 
                 0.0000105 
                 −32.4086711 
               
               
                 Cer(d18:0/22:0)/Cer(d18:1/20:0) 
                 0.0000165 
                 −31.5266149 
               
               
                 Cer(d18:0/22:0)/PS O-16:0/18:2- 
                 0.000045 
                 −37.930990 
               
               
                 alkenyl 
               
               
                 Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl 
                 0.000045 
                 −37.930990 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/20:0) 
                   
                 −26.83109 
                 80.48780 
                 64.77273 
               
               
                 Total LPC/Total LacCer 
                 0.0000469 
                 −26.08820 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/22:0) 
                   
                 −21.27116 
                 78.04878 
                 61.79775 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 12 
               
             
             
               
                   
               
               
                 Preferred embodiments from significant lipid to clinical ratios from LURIC 
               
               
                 sample sct. 
               
             
          
           
               
                 Lipid name/Clinical measurement 
                 p-value 
                 Percentage change 
                 Sensitivity 
                 Specificity 
               
               
                   
               
             
          
           
               
                 Positive correlation 
                   
                   
                   
                   
               
               
                 Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00000 
                 43.22923 
               
               
                 Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 0.00000 
                 36.15491 
                 69.56522 
                 60.34483 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 47.52465 
                 77.27273 
                 67.00000 
               
               
                 Total Cer/apolipoprotein A-I (mg/dL) 
                 0.00016 
                 25.36811 
               
               
                 Total LacCer/apolipoprotein A-I (mg/dL) 
                 0.00031 
                 28.05057 
                 71.73913 
                 61.53846 
               
               
                 Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 49.43693 
               
               
                 LacCer(d18:1/22:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 35.92744 
               
               
                 LacCer(d18:1/20:0)/HDL cholesterol (EDTA) 
                   
                 39.32664 
                 72.72727 
                 61.00000 
               
               
                 (mg/dL) 
               
               
                 Cer(d18:1/24:1)/apolipoprotein B (mg/dL) 
                   
                 18.05222 
                 82.60870 
                 62.06897 
               
               
                 Negative correlation 
               
               
                 Cer(d18:0/24:0)/apolipoprotein B (mg/dL) 
                 0.03428 
                 −21.10483 
               
               
                 Cer(d18:0/24:0)/total cholesterol (EDTA) 
                 0.04309 
                 −19.71324 
               
               
                 (mg/dL) 
               
               
                 Cer(d18:0/24:0)/apolipoprotein B (mg/dL) 
                 0.00181 
                 −26.25271 
               
               
                 PC 16:0/20:4/apolipoprotein B (mg/dL) 
                 0.00576 
                 −15.39247 
               
               
                 Cer(d18:0/24:0)/apolipoprotein A-I (mg/dL) 
                 0.01052 
                 −22.39254 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                 Top candidates from each category, if available, are listed. The best 
               
               
                 candidates were selected based on following criteria: t-test p-value 
               
               
                 ≦0.05 and sensitivity ≧60% and specificity ≧60%. 
               
             
          
           
               
                   
                   
                 Percentage 
               
               
                 Measurement name 
                 p-value 
                 change 
               
               
                   
               
             
          
           
               
                 Positive correlation 
                   
                   
               
               
                 Cer(d18:1/20:0) 
                 0.00004 
                 28.00357 
               
               
                 LacCer(d18:1/20:0) 
                 0.00010 
                 32.91154 
               
               
                 Cer(d18:1/24:1) 
                 0.00039 
                 23.37606 
               
               
                 LacCer(d18:1/24:1) 
                 0.00199 
                 29.83279 
               
               
                 LacCer(d18:1/22:0) 
                 0.00046 
                 22.75541 
               
               
                 Cer(d18:1/18:0) 
                 0.00009 
                 34.32550 
               
               
                 Cer(d18:1/24:1)/PC 16:0/20:4 
                 0.000000 
                 59.876132 
               
               
                 LacCer(d18:1/20:0)/PC 16:0/20:3 
                 0.000008 
                 56.972652 
               
               
                 PS O-16:0/18:2-alkenyl/Total PS O 
                   
                 26.42621 
               
               
                 Cer(d18:1/18:0)/PC 16:0/20:4 
                 0.000000 
                 73.073704 
               
               
                 Cer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00000 
                 43.22923 
               
               
                 Cer(d18:1/24:1)/apolipoprotein A-I (mg/dL) 
                 0.00000 
                 36.15491 
               
               
                 LacCer(d18:1/20:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 47.52465 
               
               
                 Total LacCer/apolipoprotein A-I (mg/dL) 
                 0.00031 
                 28.05057 
               
               
                 LacCer(d18:1/20:0)/HDL cholesterol (EDTA) 
                   
                 39.32664 
               
               
                 (mg/dL) 
               
               
                 Cer(d18:1/18:0)/apolipoprotein A-I (mg/dL) 
                 0.00001 
                 49.43693 
               
               
                 Negative correlation 
               
               
                 PC 16:0/20:4 
                 0.02256 
                 −14.96966 
               
               
                 Cer(d18:0/24:0) 
                 0.03376 
                 −21.87004 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/20:0) 
                   
                 −26.83109 
               
               
                 DAG 16:0/18:1/Total DAG 
                   
                 −17.30528 
               
               
                 Cer(d18:0/24:0)/Total Cer 
                   
                 −31.45318 
               
               
                 Total LPC/Total LacCer 
                   
                 −26.08820 
               
               
                 GlcCer(d18:1/26:0)/LacCer(d18:1/22:0) 
                   
                 −21.27116 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/24:1) 
                 0.0000004 
                 −36.1288066 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/18:0) 
                 0.0000052 
                 −40.2960344 
               
               
                 Cer(d18:0/24:0)/PS O-16:0/18:2-alkenyl 
                 0.0000059 
                 −40.8329837 
               
               
                 Cer(d18:0/24:0)/Cer(d18:1/22:0) 
                 0.0000105 
                 −32.4086711 
               
               
                 Cer(d18:0/22:0)/PS O-16:0/18:2-alkenyl 
                 0.000045 
                 −37.930990 
               
               
                 Cer(d18:0/22:0)/PS O-16:1/18:2-alkyl 
                 0.000045 
                 −37.930990 
               
               
                 Cer(d18:0/24:0)/LacCer(d18:1/24:0) 
                 0.0000067 
                 −37.0287234 
               
               
                   
               
             
          
         
       
     
         [0136]    Lipidomic analysis proved to be efficient in identifying novel plasma biomarkers for CVD complications. 
         [0137]    Molecular lipid to molecular lipid ratio could be an important indicator of cellular lipid metabolism including e.g., enzyme activities in the lipid metabolism pathways. Thus, these ratios may provide more information as the absolute plasma concentrations of the molecular lipids alone. As the absolute molecular lipid plasma concentration differences in general between healthy individuals and atherosclerotic patients seem to be between 30-70%, it might be reasonable to calculate and use different ratios instead of absolute concentrations only. As lipoprotein particles (e.g. LDL, HDL, and VLDL) are serving as carriers for most of the lipids in the blood stream it is appropriate to relate molecular lipid concentrations to lipoprotein data. Thus, the molecular lipid to HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I and apolipoprotein B ratios were calculated. In fact, a number of ratios between the concentrations of different molecular lipids outperformed absolute plasma concentrations as disease biomarkers in CVD patients. 
         [0138]    As the detected lipids are carried in the lipoprotein particles (LDL, VLDL and HDL) it is obvious that the corresponding lipoprotein fraction concentrations will even improve the prediction potential of molecular lipids from the results of the present study in total serum/plasma samples. 
         [0139]    The lipid lowering drug efficiency measurements have so far been based on LDL-C and HDL-C assays. As the inventors have herein observed more potential biomarkers that predict the development of high-risk CVD complications better than these classical analyses, future drug efficiency profiling should be based on new sensitive and specific biomarkers that are more directly related to the risk of severe CVD-related complications rather than to LDL-C. 
         [0140]    Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific embodiments described herein both in the Examples in the body of the entire patent description. Such equivalents are considered to be within the scope of this invention and are covered by the following claims.