Low-Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a). Should both HDL-C and LDL-C be targets for lipid therapy? A review of current evidence. Canadian Cardiovascular Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Effects of Prescription Omega-3-Acid Ethyl Esters on Fasting Lipid Profile in Subjects With Primary Hypercholesterolemia Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial. Effects on lipoprotein particles of long-term dehydroepiandrosterone in elderly men and women and testosterone in elderly men. Extended-release niacin reduces LDL particle number without changing total LDL cholesterol in patients with stable CAD. Extended-release niacin/laropiprant effects on lipoprotein subfractions in patients with type 2 diabetes mellitus. An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL particle number in hypertriglyceridemic men - a nuclear magnetic resonance study. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia. The effects of extended release niacin on lipoprotein sub-particle concentrations in HIV-infected patients. Effects of simvastatin and ciprofibrate alone and in combination on lipid profile, plasma fibrinogen and low density lipoprotein particle structure and distribution in patients with familial combined hyperlipidaemia and coronary artery disease The Lipoprotein and Coronary Atherosclerosis Study (LCAS): design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia. Substituting Walnuts for Monounsaturated Fat Improves the Serum Lipid Profile of Hypercholesterolemic Men and Women Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes. Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).
Background — Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease ( CHD ) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial ( VA-HIT ) . We examined whether measurement of low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) particle subclasses provides additional information relative to CHD risk reduction . Methods and Results — This is a prospect i ve nested case-control study of 364 men with a new CHD event ( nonfatal myocardial infa rct ion or cardiac death ) during a 5.1-year ( median ) follow-up and 697 age-matched controls .  Nuclear magnetic resonance ( NMR ) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo . Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models . Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles ( −5 % ) while raising numbers of HDL particles ( 10 % ) and small HDL subclass particles ( 21 % ) . Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant , independent predictors of new CHD events . For total LDL and HDL particles , odds ratios predicting CHD benefit were 1.28 ( 95 % CI , 1.12 to 1.47 ) and 0.71 ( 95 % CI , 0.61 to 0.81 ) , respectively . Mean LDL and HDL particle sizes were not associated with CHD events . Conclusions — The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses , which are not reflected by conventional lipoprotein cholesterol measures , help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol OBJECTIVES To test the hypothesis that a garlic supplement alters plasma lipoproteins , postpr and ial lipemia , low-density lipoprotein ( LDL ) size and high-density lipoprotein ( HDL ) subclass distribution differently in 50 moderately hypercholesterolemic subjects classified as LDL subclass pattern A or B. BACKGROUND Garlic has been variably reported to reduce or not affect plasma cholesterol values . Low-density lipoprotein pattern B is a common inherited disorder of lipoprotein metabolism that has been shown to have a significantly greater response to several lipid lowering treatments including low fat diet when compared with LDL pattern A individuals . METHODS A double blind , r and omized , placebo controlled trial in an outpatient lipid research clinic was performed and included fifty moderately hypercholesterolemic subjects ( mean LDL cholesterol = 166 + /- 22 mg/dl ) classified as LDL subclass pattern A ( predominantly large LDL , n = 22 ) or B ( predominantly small LDL , n = 28 ) . Following a two-month stabilization period , subjects were r and omly assigned to a placebo or 300 mg three times a day of a st and ardized garlic tablet for three months . RESULTS For all subjects , LDL pattern A and B subjects combined , garlic treatment for three months result ed in no significant change in total cholesterol , LDL cholesterol , HDL cholesterol , HDL subclass distribution , postpr and ial triglycerides , apolipoprotein B , lipoprotein ( a ) ( Lp[a ] ) , LDL peak particle diameter or LDL subclass distribution . There was no significant difference in response for the same parameters among subjects classified as LDL pattern A or B with the exception of significantly greater ( p = 0.01 ) reduction in mean peak particle diameter in pattern A subjects treated with either garlic or placebo . There was no significant change in LDL subclass distribution . CONCLUSIONS This investigation confirms that garlic therapy has no effect on major plasma lipoproteins and further , that it has no impact on HDL subclasses , Lp(a ) , apolipoprotein B , postpr and ial triglycerides or LDL subclass distribution .  Garlic may have a greater effect on LDL particle diameter in LDL pattern A compared with pattern B subjects . This difference was not reflected in other plasma lipid measurements The current guidelines for treatment of high-risk of lipid disorders do not specify a therapeutic target level of high-density lipoprotein cholesterol ( HDL-C ) for prevention of vascular disease in high-risk population s. However , there is a substantial body of evidence from basic science and epidemiologic studies and from clinical trials , providing the strong , consistent message that raising HDL-C by therapeutic means will effectively and independently reduce cardiovascular risk . This review summarizes epidemiologic evidence and the results of a meta- analysis of 23 published , prospect i ve , r and omized , placebo-controlled clinical trials . It focuses on the effects of lipid therapies on coronary stenosis progression , as measured by quantitative arteriography and /or , on clinical cardiovascular endpoints . Among the seven drug/treatment classes into which individual study results were categorized and averaged , reduction in stenosis progression and reduction in clinical events are both very highly correlated with the composite lipid variable ( % ΔHDL-C - % Δ low-density lipoprotein cholesterol [ LDL-C ] ; where % Δ is percent change relative to the placebo group response ) . This holds true for all lipid drug classes or combinations of lipid drug therapy , with the exception of the unexpectedly anomalous effects of the torcetrapib-atorvastatin combination . There is a strong and consistent body of evidence that therapeutic HDL-C-raising is at least as effective as comparable percentages of LDL-C-lowering for reduction of atherosclerosis progression or clinical cardiovascular events over a broad range of risk levels . Adoption of this strategy into guidelines probably awaits results of at least one large controlled HDL-C-raising clinical trial , of which two are ongoing and one other is planned Since the last publication of the recommendations for the management and treatment of dyslipidemia , new clinical trial data have emerged that support a more vigorous approach to lipid lowering in specific patient groups . The decision was made to up date the lipid guidelines in collaboration with the Canadian Cardiovascular Society . A systematic electronic search of medical literature for original research consisting of blinded , r and omized controlled trials was performed . Meta-analyses of studies of the efficacy and safety of lipid-lowering therapies , and of the predictive value of established and emerging risk factors were also review ed . All recommendations are evidence -based , and have been review ed in detail by primary and secondary review panels . Major changes include a lower low-density lipoprotein cholesterol ( LDL-C ) treatment target ( lower than 2.0 mmol/L ) for high-risk patients , a slightly higher intervention point for the initiation of drug therapy in most low-risk individuals ( LDL-C of 5.0 mmol/L or a total cholesterol to high-density lipoprotein cholesterol ratio of 6.0 ) and recommendations regarding additional investigations of potential use in the further evaluation of coronary artery disease risk in subjects in the moderate-risk category This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia . This was a multicenter , r and omized , open-label , parallel- design study of patients with total cholesterol > 200 mg/dl , triglycerides between 200 and 800 mg/dl , and apolipoprotein B > 110 mg/dl . Patients were r and omly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg daily for 12 weeks following a low-fat diet stabilization period . Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy . Atorvastatin and niacin both significantly reduced the concentrations of very low-density lipoprotein ( VLDL ) particles ( -31 % and -29 % , respectively ) and small low-density lipoprotein ( LDL ) particles ( -44 % and -35 % , respectively ) . Niacin increased the concentration of large LDL ( + 75 % ) . Atrovastatin reduced the number of LDL particles more than niacin ( 31 % vs 14 % ) . In patients with atherogenic dyslipidemia , both drugs had important effects on lipoprotein subfractions , which contributed to a reduction in coronary heart disease risk . The drugs equally reduced VLDL subclass levels . Niacin shifted the LDL subclass distribution toward the larger particles , more effectively converted patients from LDL phenotype B to phenotype A , and increased levels of the larger and perhaps more cardioprotective high-density lipoprotein particles . In contrast , atorvastatin preferentially lowered the concentration of small LDL particles without increasing levels of large LDL , and more effectively , reduced LDL particle numbers .  Atorvastatin had a preferred LDL effect , whereas niacin had a preferred high-density lipoprotein effect This double-blind , r and omized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters ( POM3 , 4 g/day ) versus placebo ( soy oil ) on low-density lipoprotein cholesterol ( LDL-C ) and other aspects of the fasting lipid profile in 31 men and women with primary , isolated hypercholesterolemia ( LDL-C 130 - 220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies ) . Mean ± st and ard error of the mean baseline concentrations of total cholesterol , LDL-C , high-density lipoprotein cholesterol ( HDL-C ) , very-low-density lipoprotein cholesterol , and triglycerides were 229 ± 3 , 146 ± 3 , 60 ± 2 , 23 ± 2 , and 113 ± 8 mg/dL , respectively . POM3 produced a modest increase from baseline in LDL-C ( 3.4 % ) versus the placebo response ( -0.7 % , P = 0.010 ) . Significant changes ( P < 0.05 ) for POM3 ( placebo-corrected ) were observed for very-low-density lipoprotein cholesterol ( -18.8 % ) , triglycerides ( -18.7 % ) , and HDL-C ( 3.3 % ) . Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo , whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo . Total cholesterol , non-HDL-C , apolipoproteins A1 and B , and LDL particle concentration responses did not differ between treatments . These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary , isolated hypercholesterolemia . Effects on other variables were consistent with prior results in mixed dyslipidemia Objective : To compare the effects of combination niacin extended-release + simvastatin ( NER/S ) versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME , a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia . Patients and methods : Patients ( n = 137 ) with dyslipidemia ( not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study ) received NER/S ( 1000/40 mg/day for four weeks , then 2000/40 mg/day for eight weeks ) or atorvastatin 40 mg/day for 12 weeks . Median percent changes in apolipoprotein ( apo ) A-1 , apo B , and the apo B : A-I ratio , and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher ’s exact test . Results : NER/S treatment produced significantly greater percent changes in apo A-I and apo B : A-I , and , at the final visit , apo B < 80 mg/dL was attained by 59 % versus 33 % of patients , compared with atorvastatin treatment ( P = 0.003 ) . NER/S treatment result ed in greater percent reductions in calculated particle numbers for low-density lipoprotein ( LDL , 52 % versus 43 % ; P = 0.022 ) , small LDL ( 55 % versus 45 % ; P = 0.011 ) , very low-density lipoprotein ( VLDL ) and total chylomicrons ( 63 % versus 39 % ; P < 0.001 ) , and greater increases in particle size for LDL ( 2.7 % versus 1.0 % ; P = 0.007 ) and VLDL ( 9.3 % versus 0.1 % ; P < 0.001 ) , compared with atorvastatin . Conclusion : NER/S treatment significantly improved apo A-I levels and the apo B : A-I ratio , significantly lowered the number of atherogenic LDL particles and VLDL and chylomicron particles , and increased the mean size of LDL and VLDL particles , compared with atorvastatin Lipoprotein subclass measurements may enhance the prediction of coronary artery disease ( CAD ) risk , but clinical application of such information has been hindered by the relatively laborious and time-consuming nature of laboratory measurement methods . In this study , lipoprotein subclass analyses were performed on frozen plasma sample s from 241 participants in the Pravastatin Limitation of Atherosclerosis in the Coronary arteries Trial using an automated nuclear magnetic resonance technique . The objective was to determine if levels of these subclasses provided additional information on the progression of CAD , based on the change in the minimum lumen diameter , over a 3-year period . After adjustment for race , sex , age , treatment group , baseline lumen diameter , and chemically measured levels of triglycerides , low-density lipoprotein ( LDL ) cholesterol , and high-density lipoprotein ( HDL ) cholesterol , on-trial predictors ( p < 0.05 ) of progression included an elevated LDL particle number , and levels of small LDL and small HDL . Within treatment groups , CAD progression was most strongly related to the LDL particle number  ( placebo ) and levels of small HDL  ( pravastatin ) . In logistic regression models that adjusted for chemically determined lipid levels and other covariates , a small LDL level > or = 30 mg/dl ( median ) was associated with a ninefold increased risk of CAD progression ( p < 0.01 ) in the placebo group . These results indicate that levels of various lipoprotein subclasses may provide useful information on CAD risk even if levels of traditional risk factors are known BACKGROUND The DASH ( Dietary Approaches to Stop Hypertension ) dietary pattern , which is high in fruit , vegetables , and low-fat dairy foods , significantly lowers blood pressure as well as low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol . OBJECTIVE The study was design ed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet , with a corresponding increase in fat and a reduction in sugar intake , on blood pressure and plasma lipids and lipoproteins . DESIGN This was a 3-period r and omized crossover trial in free-living healthy individuals who consumed in r and om order a control diet , a st and ard DASH diet , and a higher-fat , lower-carbohydrate modification of the DASH diet ( HF-DASH diet ) for 3 wk each , separated by 2-wk washout periods . Laboratory measurements , which included lipoprotein particle concentrations determined by ion mobility , were made at the end of each experimental diet . RESULTS Thirty-six participants completed all 3 dietary periods . Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet . The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein ( VLDL ) particle concentrations and increased LDL peak particle diameter compared with the DASH diet . The DASH diet , but not the HF-DASH diet , significantly reduced LDL cholesterol , HDL cholesterol , apolipoprotein A-I , intermediate-density lipoprotein and large LDL particles , and LDL peak diameter compared with the control diet . CONCLUSIONS The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol . This trial was registered at clinical trials.gov as NCT01404897 CONTEXT Although age-related declines in dehydroepi and rosterone sulfate ( DHEAS ) and testosterone are associated with cardiovascular risk , it remains to be determined whether replacement of these hormones improves cardiovascular risk factors . OBJECTIVE This study sought to determine the effect of long-term replacement of dehydroepi and rosterone ( DHEA ) in elderly men and women and testosterone in elderly men on lipid and lipoprotein concentrations and particle sizes . METHODS A 2-yr r and omized , placebo-controlled , double-blind study was conducted in 87 elderly men with low levels of DHEAS and bioavailable testosterone and 57 elderly women with low levels of DHEAS . Among elderly men , 29 received DHEA ( 75 mg/d ) , 27 received testosterone ( 5 mg/d ) , and 31 received placebo . Among the elderly women , 27 received DHEA ( 50 mg/d ) , and 30 received placebo . Baseline lipoprotein profiles in the elderly were compared to healthy younger participants .  Low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) particle sizes and concentrations were quantified using nuclear magnetic resonance spectroscopy . RESULTS The elderly had higher concentrations of total cholesterol , triglycerides , LDL cholesterol , total LDL particles , and small , dense LDL particles than the young . In men , neither DHEA nor testosterone affected LDL or HDL particle concentrations . In women , DHEA reduced HDL cholesterol [ median difference ( 95 % confidence intervals ) , -5.0 ( -8.0 , -2.0 ) mg/dl ; P = 0.002 ] and the number of large HDL particles [ -1.0 ( -1.8 , -0.2 ) micromol/liter ; P = 0.003 ] . CONCLUSIONS Long-term DHEA and testosterone had no significant effect on plasma lipoproteins in elderly men , but elderly women showed a lowering of the large HDL particles that may have potential adverse clinical implication BACKGROUND The importance of the number of circulating low-density lipoprotein ( LDL ) cholesterol particles , in addition to total LDL level , has been increasingly recognized . The effects of extended-release niacin ( ERN ) on LDL particle numbers have not been studied . OBJECTIVE To evaluate ERN 's effects on LDL particle numbers . METHODS Fifty-four patients with stable coronary artery disease ( CAD ) and well-controlled LDL levels were r and omly assigned to 3 months of ERN ( 1 g/day ) or placebo in addition to their baseline medications . Lipoprotein particle number was analyzed by proton nuclear magnetic resonance spectroscopy at baseline and after 3 months . RESULTS Compared to baseline , the addition of ERN had no significant effect on total LDL cholesterol levels ; however , ERN decreased the number of medium and small LDL particles ( P < .005 ) . After 3 months , ERN decreased the number of medium and small LDL particles compared to placebo-treated patients ( P < .05 ) . ERN raised HDL cholesterol levels by 2.7 % , significantly increased the number of large HDL particles ( P < .001 ) , and decreased the number of small HDL particles ( P = .027 ) compared to placebo . There were no significant changes in lipid values or particle numbers in the placebo-treated patients . In patients with stable coronary artery disease and well-controlled LDL cholesterol levels , ERN reduced the number of circulating particles of the more atherogenic subtypes of LDL , despite having no effect on total LDL cholesterol levels .  ERN also favorably altered the number of HDL particles . CONCLUSION ERN-induced alterations in lipoprotein particle numbers may contribute to its anti-atherosclerotic effects , and these effects may not be evident from the st and ard lipid profile BACKGROUND A potentially atherogenic lipid profile often found in patients with type 2 diabetes mellitus ( T2DM ) includes increased concentrations of small , low-density lipoprotein ( LDL ) and intermediate-density lipoprotein ( IDL ) and decreased concentration of medium/large high-density lipoprotein ( HDL ) particles . Extended-release niacin/laropiprant ( ERN/LRPT ) lowers LDL-cholesterol ( LDL-C ) and triglycerides ( TG ) , and raises HDL cholesterol ( HDL-C ) levels with attenuation of niacin-induced flushing . METHODS Plasma HDL , LDL , IDL , very-low-density lipoprotein ( VLDL ) , and chylomicron particle concentration and size at were evaluated at baseline and week 12 using nuclear magnetic resonance ( NMR ) . The data were acquired from a r and omized , multicenter , double-blind , placebo-controlled study including 796 patients with T2DM treated with either 1 tablet of ERN 1 gram/LRPT 20 mg or matching placebo  daily , increased after 4 weeks to 2 tablets daily . RESULTS ERN/LRPT significantly ( P≤0.001 for all ) reduced LDL-C 17.9 % and TG 23.1 % , and increased HDL-C levels 23.2 % . Compared to placebo , ERN/LRPT decreased LDL , IDL , VLDL , and chylomicron particle concentrations [ median concentration of smallest LDL particles decreased 16.6 % , 95 % confidence interval ( CI ) -22.3 , -10.9 , whereas the largest LDL particles decreased 11.0 % , 95 % CI -18.7 , -3.2 , and total VLDL/chylomicron mean plasma particle concentration decreased 34.7 % , 95 % CI -41.3 , -28.1 ] . Compared to placebo , ERN/LRPT shifted the distribution of HDL particle diameter from smaller to larger ( median concentration of the largest HDL particles increased 32.7 % ( 95 % CI 25.30 , 40.58 ) , whereas concentration of the smallest HDL particles decreased 8.2 % ( 95 % CI -11.29 , -5.06 ) . CONCLUSIONS Compared with placebo in patients with T2DM , ERN/LRPT shifted the lipoprotein profile toward a potentially less atherogenic pattern with reduced atherogenic LDL and IDL particle concentrations , and increased large HDL plasma particle concentrations . ( Clinical Trials.gov : NCT00485758 ) We investigated the effect of olive oil , rapeseed oil , and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses .  Eighteen young , healthy men participated in a double-blinded r and omized cross-over study ( 3-week intervention period ) with 50 g of oil per 10 MJ incorporated into a constant diet .  Plasma cholesterol , triacylglycerol , apolipoprotein B , and very low density lipoprotein ( VLDL ) , intermediate density lipoprotein ( IDL ) , and low density lipoprotein ( LDL ) cholesterol concentrations were 10;-20 % higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [ analysis of variance ( ANOVA ) , P < 0.05 ] . The size of IDL , VLDL , and LDL subfractions did not differ between the diets , whereas a significantly higher number ( apolipoprotein B concentration ) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets ( ANOVA , P < 0.05 ) . Total HDL cholesterol concentration did not differ significantly , but HDL(2a ) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil ( ANOVA , P < 0.05).In conclusion , rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil . Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils BACKGROUND Icosapent ethyl ( IPE ; formerly AMR101 ) is a high-purity prescription form of eicosapentaenoic acid ethyl ester . In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides ( TG ; ≥500 mg/dL ) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein ( LDL ) cholesterol levels  . OBJECTIVES In this follow-up , exploratory analysis , we report the effects of IPE on lipoprotein particle concentration and size . METHODS MARINE was a phase 3 , multicenter , placebo-controlled , r and omized , double-blind , 12-week study . Hypertriglyceridemic patients ( N = 229 ) were r and omized to three treatment groups : IPE 4 g/day , IPE 2 g/day , or placebo . Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy . RESULTS Compared with placebo , IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein ( VLDL ; -27.9 % ; P = .0211 ) , total LDL ( -16.3 % ; P = .0006 ) , small LDL ( -25.6 % ; P < .0001 ) , and total high-density lipoprotein ( HDL ; -7.4 % ; P = .0063 ) particles and reduced VLDL particle size ( -8.6 % ; P = .0017 ) . In this patient population with TG ≥500 mg/dL , IPE did not significantly change the overall sizes of LDL or HDL particles . CONCLUSION IPE 4 g/day significantly reduced large VLDL , total LDL , small LDL , and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid . The reduction in LDL particle concentration  with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels . CLINICAL TRIAL REGISTRATION NUMBER NCT01047683 Hypertriglyceridemia is often associated with small dense low density lipoprotein ( LDL ) , elevated remnants , and decreased high density lipoprotein (HDL)-cholesterol ( C ) , which comprise the dyslipidemic triad . The objective of this study was to investigate the effect of fenofibrate on the lipoprotein subfraction profile and inflammation markers in hypertriglyceridemic men . Twenty hypertriglyceridemic men were administered fenofibrate , 200 mg daily , for 8 weeks . Lipoprotein subclasses were measured by nuclear magnetic resonance ( NMR ) spectroscopy . Inflammation markers including C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and monocyte chemotactic protein-1 ( MCP-1 ) were also determined . Fenofibrate lowered triglyceride ( TG ) by 58 % and increased HDL-C by 18 % . NMR analysis revealed that very low density lipoprotein ( VLDL ) , particularly large VLDL , intermediate density lipoprotein ( IDL ) , and small LDL , were significantly decreased , and LDL distribution shifted towards the larger particles . HDL distribution was altered ; there was an increase in small HDL and a decrease in large HDL , result ing in a significant decrease in HDL particle size , from 9.1 to 8.9 nm , as well as a 27 % increase in HDL particle number . Among inflammation markers , CRP was significantly decreased by 42 % . In conclusion , fenofibrate effectively improves atherogenic dyslipidemia by reducing remnants and small LDL , as well as by increasing HDL particles . These effects , together with the favorable effect on inflammation , might provide a clinical benefit in hypertriglyceridemic subjects BACKGROUND the effects of smoking and smoking cessation on lipoproteins have not been studied in a large contemporary group of smokers . This study was design ed to determine the effects of smoking cessation on lipoproteins . METHODS this was a 1-year , prospect i ve , double-blind , r and omized , placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies . Fasting nuclear magnetic resonance spectroscopy lipoprotein profiles were obtained before and 1 year after the target smoking cessation date . The effects of smoking cessation and predictors of changes in lipoproteins after 1 year were identified by multivariable regression . RESULTS the 1,504 current smokers were ( mean [ SD ] ) 45.4 ( 11.3 ) years old and smoked 21.4 ( 8.9 ) cigarettes per day at baseline . Of the 923 adult smokers who returned at 1 year , 334 ( 36.2 % ) had quit smoking . Despite gaining more weight ( 4.6 kg [ 5.7 ] vs 0.7 kg [ 5.1 ] , P < .001 ] , abstainers had increases in high-density lipoprotein cholesterol ( HDL-C ) ( 2.4 [ 8.3 ] vs 0.1 [ 8.8 ] mg/dL , P < .001 ) , total HDL ( 1.0 [ 4.6 ] vs -0.3 micromol/L [ 5.0 ] , P < .001 ) , and large HDL ( 0.6 [ 2.2 ] vs 0.1 [ 2.1 ] micromol/L , P = .003 ) particles compared with continuing smokers . Significant changes in low-density lipoprotein ( LDL ) cholesterol and particles were not observed . After adjustment , abstinence from smoking ( P < .001 ) was independently associated with increases in HDL-C and total HDL particles . These effects were stronger in women . CONCLUSIONS despite weight gain , smoking cessation improved HDL-C , total HDL , and large HDL particles , especially in women . Smoking cessation did not affect LDL or LDL size . Increases in HDL may mediate part of the reduced cardiovascular disease risk observed after smoking cessation Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque . Oxidized low-density lipoprotein particles ( Ox-LDL ) have a key role in the pathogenesis of atherosclerosis . The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention . We conducted a r and omized double-blind placebo-controlled crossover clinical trial . Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract ( RGSE ) or placebo for 8 weeks . After an 8-week washout period , the groups were crossed over for another 8 weeks . Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase . RGSE consumption reduced total cholesterol ( -10.68±26.76 mg/dL , P=.015 ) , LDL cholesterol ( -9.66±23.92 mg/dL , P=.014 ) , and Ox-LDL ( -5.47±12.12 mg/dL , P=.008 ) . While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE , the changes were not statistically significant . RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals With the advent of highly active antiretroviral therapy ( HAART ) , Cardiovascular Disease ( CVD ) has emerged as the leading cause of death in Human Immunodeficiency Virus ( HIV ) infected patients . An atherogenic lipoprotein phenotype has been described in HIV- infected patients with a predominance of small , low density lipoprotein ( SLDL ) particles with accompanying elevated triglycerides and reduced high density lipoprotein cholesterol . This r and omized controlled pilot study was conducted to evaluate the efficacy of Extended Release Niacin ( ERN ) in improving the lipid profile in HIV patients . A total of 17 HIV positive subjects on HAART therapy with High Density Lipoprotein Cholesterol ( HDL ) levels below 40mg/dl and Low Density Lipoprotein Cholesterol ( LDL ) below 130mg/dl were enrolled . Nine were r and omized to be treated with ERN titrated from a starting level of 500mg/night and titrated to a level of 1500mg/night . Eight patients were assigned to the control arm . No placebo was used . Lipoprotein profiles of the subjects were analyzed at baseline and at the end of 12 weeks using Nuclear Magnetic Resonance ( NMR ) spectroscopy . At the end of 12 weeks , NMR spectroscopic analysis revealed a significant increase in overall LDL size ( 1.2 % in ERN treated subjects vs 2.0 % decrease in control patients , P=.04 ) and a decrease in small LDL particle concentration ( 17.0 % in ERN treated subjects vs 21.4 % increase in control patients , P=.03 ) in subjects receiving ERN as compared to those in the control group . Only 1 subject receiving ERN developed serious flushing which was attributed to an accidental overdose of the drug . This pilot study demonstrates that ERN therapy in HIV-infected patients with low HDL is safe and effective in improving the lipoprotein profile in these patients Background Hypolipidaemic agents do not usually normalize all of the multiple lipoprotein abnormalities in patients with familial combined hyperlipidaemia ( FCHL ) . The effect of the simvastatin-ciprofibrate combination in comparison with each drug alone on the lipoprotein abnormality patterns was studied in patients with FCHL and coronary artery disease ( CAD ) . Methods Sixty patients ( 53 men and seven women ) , mean age 52 years ( range 36–60 years ) , were studied . After a 4-week placebo period , patients were r and omly assigned to three groups . The first group ( n = 20 ) received simvastatin ( 20 mg daily ) , the second group ( n = 20 ) ciprofibrate ( 100 mg daily ) and the third group ( n = 20 ) the combination of both drugs for a 1 2-week period . Parameters measured were as follows : plasma fibrinogen , total cholesterol , triglycerides , low density lipoprotein ( LDL ) , very low density lipoprotein , intermediate density lipoprotein , and high density lipoprotein cholesterol , as well as LDL subfraction distribution and structure by density gradient ultracentrifugation . Apoproteins ( apo ) B and Al were assessed by immunoturbidometry . Results At baseline , apoB , LDL cholesterol and triglycerides were increased , whereas LDL particles were small and dense . ApoB was significantly reduced by all three interventions . Drug combination and ciprofibrate significantly reduced plasma fibrinogen ( -24 and −25 % , respectively ; P < 0.001 ) and triglycerides ( -51 and −49 % , respectively ; P < 0.001 ) . Drug combination and simvastatin significantly reduced LDL cholesterol ( -25 and −22 % , respectively ; P < 0.001 ) compared with ciprofibrate ( -10 % ; P<0.01 ) . Ciprofibrate and drug combination  increased LDL particle size ( parameter K −0.24 versus −0.61 and −0.30 versus −0.62 , respectively ; P < 0.001 ) , whereas simvastatin had no significant effect on LDL particle size . The cholesterol content of LDL particles was reduced with ciprofibrate and the drug combination only in the dense LDL particles ( LDL3–5 ) and increased in the light ( LDL1–2 ) subfractions , whereas simvastatin reduced the cholesterol content of all LDL subfractions except LDL2 . Ciprofibrate and drug combination reduced the triglyceride content of al ! LDL subfractions . Conclusion Combined treatment with simvastatin and ciprofibrate  effectively reduced plasma fibrinogen , triglycerides , total and LDL cholesterol and increased LDL particle size in patients with FCHL and CAD . These effects might induce a clinical benefit for these patients Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease ( CHD ) and normal or only slightly elevated plasma cholesterol concentrations . The one published angiographic trial design ed to examine this question found no benefit . Additional prospect i ve data will be provided by the Lipoprotein and Coronary Atherosclerosis Study ( LCAS ) , a r and omized , double-blind , placebo-controlled trial of fluvastatin therapy ( 20 mg twice daily ) monitored by both quantitative coronary angiography ( QCA ) and , in a subset of patients , positron-emission tomography ( PET ) .  Eligible subjects in LCAS were men and women 35 - 75 years of age with low-density lipoprotein ( LDL ) cholesterol of 115 - 190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30 - 75 % diameter stenosis . Among the 429 patients r and omized ( mean age 58.8 , 81 % male ) , mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prer and omization  LDL cholesterol  of 160 mg/dL or higher also received open-label adjunctive cholestyramine . The primary endpoint is within-patient per-lesion change in minimum lumen diameter ( MLD ) as measured by QCA at baseline and 2.5-year follow-up . All evaluable lesions had MLD at least 0.8 mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25 % of the reference lumen diameter at baseline . Data obtained on myocardial perfusion changes ( 99 patients underwent initial PET ) , special lipid particles , and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment Lifestyle modification is the cornerstone of population -based strategies for prevention of coronary heart disease and is the first line of therapy in patients with hypercholesterolemia . Diets low in saturated fatty acids and cholesterol have long been recommended to decrease low-density lipoprotein ( LDL ) cholesterol levels and reduce cardiovascular risk ( 1 ) . Ample evidence suggests that polyunsaturated fatty acids and monounsaturated fatty acids have a similar cholesterol-lowering effect when substituted for saturated fatty acids ( 2 - 4 ) . However , most studies of fatty acids and blood lipids have been done with fats and oils , rarely with whole fatty foods . Because people usually buy and consume whole food products , it is desirable to know the effects of specific foods on risk factors for coronary heart disease . Recent reports suggest that the regular consumption of nuts might reduce cardiovascular risk ( 5 ) . Walnuts are particularly rich in polyunsaturated fatty acids ( 6 ) , and epidemiologic evidence suggests that frequent walnut consumption protects against coronary heart disease ( 7 ) . In a controlled feeding trial by Sabat and colleagues ( 8) , a diet in which walnuts represented 55 % of the energy from fat reduced blood cholesterol levels in normal young men when compared with a st and ard low-fat diet . However , the results can not easily be extrapolated to the population at risk for coronary heart disease because women , older age groups , and hypercholesterolemic persons were not studied ( 8) . In addition , because meals were served at a metabolic kitchen , the study did not address the question of whether free-living persons would incorporate substantial quantities of walnuts into their diets . Because oxidized LDL plays a key role in atherogenesis ( 9 ) and oxidative damage involves peroxidation of polyunsaturated fatty acids in LDL lipids ( 10 ) , there is concern that walnut intake may promote LDL oxidation . Therefore , we design ed a dietary intervention study in free-living adult men and women with polygenic hypercholesterolemia to compare the effects of a walnut-rich diet with those of a cholesterol-lowering Mediterranean diet on serum lipid levels , lipoprotein levels , and LDL resistance to oxidation . Methods Patients Adult men and women with polygenic hypercholesterolemia attending the Lipid Clinic of the Hospital Clnic of Barcelona were eligible if they had serum LDL cholesterol concentrations greater than 3.36 mmol/L ( 130 mg/dL ) and triglyceride concentrations less than 2.82 mmol/L ( 250 mg/dL ) ; no evidence of alcohol , tobacco , or drug abuse ; absence of diabetes mellitus and liver , kidney , thyroid , or other endocrine diseases , as assessed by medical history , a complete physical examination , and laboratory tests ; no intake in the previous 8 weeks of medications known to affect lipid metabolism , including hypolipidemic agents and estrogen compounds in women ; infrequent consumption of nuts and no known history of allergy to them ; and no use of multivitamin or vitamin E supplements  . Because the target population had common ( polygenic ) hypercholesterolemia , we excluded persons whose elevated blood cholesterol levels had a strong genetic basis ( such as heterozygous familial hypercholesterolemia or familial combined hyperlipidemia ) , as established by st and ard criteria . On admission to the Lipid Clinic , all patients were advised to follow a  Mediterranean-type hypolipidemic diet ( 11 ) . For a crossover design , statistical power calculations indicated that to detect mean differences of 0.39 mmol/L ( 15 mg/dL ) , 34 patients would need to complete the two treatment periods ( statistic , 0.05 ; power>0.8 ) . From a computerized register of clinical records , 75 hypercholesterolemic patients ( 35 women and 40 men ) who initially met the eligibility criteria were selected for screening and were asked to participate in the study . They were offered free walnuts but no monetary compensation . Study Design A crossover design was used . Patients were r and omly assigned to the two diet sequences by using a computer-generated r and om-number table , with stratification by sex . Because patients followed each diet for 6 weeks and lipoprotein changes due to dietary intervention stabilize in less than 4 weeks ( 12 ) , we did not incorporate a washout period between diets . In their crossover feeding study with walnuts , Sabat and colleagues ( 8) did not observe a carryover effect . In the week before the trial began , patients received expert dietary counseling individually and in a group class . Twice during the pretrial week and on weeks 5 and 6 of each one of the two dietary periods , patients came to the clinic for a medical visit , an interview with the dietitian , anthropometric measurements , and blood extraction . The main outcomes of the study were changes in serum levels of total and LDL cholesterol from the control diet period to the walnut diet period . Secondary outcomes were changes in other lipid variables and oxidizability of LDL particles . The study protocol was approved by the institutional review board of the Hospital Clnic of Barcelona , and all patients gave informed consent . Diets The experimental diets were individually prescribed and were based on estimated energy requirements . Because participants ate on their own , detailed dietary information was provided to them and , if appropriate , to their partners .  Diets were calculated in increments of 200 kcal to cover the range from 1600 to 2200 kcal . The control diet was Mediterranean and was composed of natural foodstuffs . Red meat and eggs were limited , vegetable products and fish were emphasized , olive oil was indicated for culinary use , and no nuts were allowed . The walnut diet was similar to the control diet , but walnuts partially replaced olive oil and other fatty foods . Prepackaged daily allowances of raw , shelled walnuts were provided daily in amounts varying from 41 g to 56 g ( the equivalent of 8 to 11 walnuts ) , according to the participants ' total energy intake . Walnuts were consumed as snacks or with meals in desserts or salads . In the walnut diet , walnuts contributed approximately 18 % of the total energy and 35 % of the total fat . To improve compliance , each family unit was given 1000-g packs of walnuts at the beginning of the walnut diet period .  Adherence to the study diets was carefully monitored . Unannounced 24-hour diet recalls were performed weekly by telephone during the two dietary periods , for a total of 12 recalls per patient . This method allows reliable estimations of food intake ( 13 ) . The nutrient composition of the diets was calculated with Food Processor Plus software , version 5.0 ( ESHA Research , Salem , Oregon ) , which was adapted to nutrient data bases of specific Mediterranean foods when appropriate . We defined noncompliance as at least 20 % deviation from dietary instructions regarding walnut or nutrient intake . Compliance during the walnut diet was also assessed at each clinic visit by a count of the empty walnut packages . The fatty acid content of LDL lipids was analyzed as a biological measure of adherence to the prescribed diets . Laboratory Measurements Blood sample s were obtained after an overnight fast , and serum and EDTA plasma were collected and processed immediately . Serum lipid and apolipoprotein levels were determined as described elsewhere ( 11 ) . In brief , serum cholesterol and triglyceride levels were measured by using enzymatic reagents ( Trinder , Bayer Diagnostics , Tarrytown , New York ) adapted to a Cobas Mira automated analyzer ( Hoffmann-LaRoche , Basel , Switzerl and ) . High-density lipoprotein ( HDL ) cholesterol was quantified after precipitation with phosphotungstic acid and magnesium chloride . Levels of apolipoprotein A-I and apolipoprotein B were determined by an immunoturbidimetric method ( Unimate 3 , Roche Diagnostic Systems , Basel , Switzerl and ) . Measurements of the cholesterol content of very-low-density lipoprotein particles and LDL particles were based on preparative ultracentrifugation ( 11 ) . Lipoprotein(a ) levels were measured by using an immunoturbidimetric method ( Lipoprotein[a ] SPQ II Test Kit , DiaSorin , Stillwater , Minnesota ) . To obtain the LDL fraction for fatty acid and oxidizability studies , lipoproteins were fractionated by sequential centrifugation adjusting with NaBr to separate very-low-density lipoprotein particles ( d=1.006 g/mL ) and to obtain LDL particles ( d=1.063 g/mL ) , as described elsewhere ( 14 ) . Low-density lipoprotein fatty acids were measured by capillary gas chromatography in the cholesteryl ester , phospholipid , and triglyceride lipid fractions ( 14 ) . Low-density lipoprotein susceptibility to oxidation was determined by measuring the -tocopherol content of LDL particles and conjugated diene kinetics after incubation of 50 g of LDL protein with 5 mol of copper sulfate at 37 C ( 15 , 16 ) . Statistical Analysis The two measurements obtained at baseline and at the end of each dietary period were averaged . Means and SDs are presented for each measurement . With methods described by Fleiss ( 17 ) , two-tailed t-tests were used to compare changes in outcome variables in response to dietary treatment and diet period and carryover effects for the two-period crossover design . Differences between the walnut and control diets were also tested by analysis of covariance using general linear models ; baseline values or sex were used as covariates . Analyses were performed by using SAS software ( SAS , Inc. , Cary , North Carolina ) ( 18 ) . Role of the Funding Sources The California Walnut Commission provided funding and walnuts . Research grants were also obtained from national and local nonprofit agencies . The funding sources were not involved in the design of the study and had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . None of the authors has any financial interest in the nut food industry . Results Patient Characteristics Of the 75 eligible patients , 20 left the study before r and omization for The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia . We performed a r and omized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes . Both agents significantly decreased glycosylated hemoglobin ( [ HbA1c ] P < .05 ) , fructosamine ( P < .05 ) , and the glucose-excursion curve during the oral glucose tolerance test ( [ OGTT ] P < .01 ) . With regard to the insulin curve during this test , no significant change was observed with metformin and a significant increase was measured with gliclazide ( P < .05 ) . Considering the small number of events , no significant difference was detected in the number of hypoglycemic episodes between the two agents . More upper-gastrointestinal ( GI ) symptoms were observed with metformin compared with gliclazide ( P < .05 ) . Even with no change in the st and ard lipid profile , both agents increased serum vitamin E ( P < .01 for gliclazide and P < .05 for metformin ) and decreased the level of lipid peroxidation markers in low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) particles ( P < .05 ) . Despite different mechanisms of action , gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers OBJECTIVES To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial ( BECAIT ) , we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements . BACKGROUND BECAIT , the first double-blind , placebo-controlled , r and omized serial angiographic trial of a fibrate compound , showed that progression of focal coronary atherosclerosis in young survivors of myocardial infa rct ion could be retarded by bezafibrate treatment . METHODS A total of 92 dyslipoproteinemic men who had survived a first myocardial infa rct ion before the age of 45 years were r and omly assigned to treatment for 5 years with bezafibrate ( 200 mg three times daily ) or placebo ; 81 patients underwent baseline and at least one post-treatment coronary angiography .  RESULTS In addition to the decrease in very low density lipoprotein ( VLDL ) cholesterol ( -53 % ) and triglyceride ( -46 % ) and plasma apolipoprotein ( apo ) B ( -9 % ) levels , bezafibrate treatment result ed in a significant increase in high density lipoprotein-3 ( HDL3 ) cholesterol ( + 9 % ) level and a shift in the low density lipoprotein ( LDL ) subclass distribution toward larger particle species ( peak particle diameter + 032 nm ) . The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter ( r=-0.23 , p < 0.05 ) , and percent ( % ) stenosis ( r = 0.30 , p < 0.01 ) , respectively . Decreases in small dense LDL and /or VLDL lipid concentrations were unrelated to disease progression . CONCLUSIONS Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins
Conclusions Study -level data from this systemic review establish that different lipid lowering agents can lead to discordance between LDL-P and LDL-C , therefore , basing LDL-lowering therapy only on the achievement of cholesterol goals may result in a treatment gap .
Therefore , the use of LDL-P for monitoring lipid-lowering therapy , particularly for statins , can provide a more accurate assessment of residual cardiovascular risk
Purpose This systematic review was performed to summarize published experience using low density lipoprotein particle number ( LDL-P ) to monitor the efficacy of  lipid-lowering pharmacotherapies .