Effect of 24 weeks of statin therapy on systemic and vascular inflammation in HIV-infected subjects receiving antiretroviral therapy. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Raisins and additional walking have distinct effects on plasma lipids and inflammatory cytokines The Influence of Triclosan on Biomarkers of Cardiovascular Risk in Patients in the Cardiovascular and Periodontal Study (CAPS): A Randomized Controlled Trial. Lipoprotein(a) as a cardiovascular risk factor: current status Physical activity and cardiovascular mortality risk: possible protective mechanisms? A high intake of trans fatty acids has little effect on markers of inflammation and oxidative stress in humans. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular disease risk factors: a randomized clinical trial. Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease[S] Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER. Cumulative inflammation associates with asymmetric dimethylarginine in rheumatoid arthritis: a 6 year follow-up study. Interaction between Mediterranean diet and statins on mortality risk in patients with cardiovascular disease: Findings from the Moli-sani Study. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial Circulating N‐Linked Glycoprotein Side‐Chain Biomarker, Rosuvastatin Therapy, and Incident Cardiovascular Disease: An Analysis From the JUPITER Trial Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naive individuals with HIV infection Impact of oral 1,25-dihydroxy vitamin D (calcitriol) replacement therapy on coronary artery risk factors in type 2 diabetic patients. The effect of farmed trout on cardiovascular risk markers in healthy men. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Waist circumference is related to low-grade inflammation in youth. Combined influence of cardiorespiratory fitness and body mass index on cardiovascular disease risk factors among 8-18 year old youth: The Aerobics Center Longitudinal Study. Effects of soluble fiber (Plantago ovata husk) on plasma lipids, lipoproteins, and apolipoproteins in men with ischemic heart disease. Effect of intensive lipid-lowering therapy on cardiovascular outcome in patients with and those without inflammatory joint disease.
BACKGROUND Human immunodeficiency virus (HIV)-infected individuals are at increased risk of cardiovascular disease ( CVD ) due in part to inflammation . Statins decrease inflammation in the general population , but their effect during HIV infection is largely unknown . METHODS This is an ongoing r and omized , double-blinded , placebo-controlled trial to evaluate the effect of statin therapy on inflammatory markers during HIV infection . Subjects received rosuvastatin 10 mg daily or placebo for 24 weeks . Subjects were receiving stable ( > 12 weeks ) antiretroviral therapy and had a low-density lipoprotein ( LDL ) cholesterol level of ≤130 mg/dL and evidence of heightened immune activation or inflammation . This was a prespecified interim analysis . RESULTS A total of 147 subjects were enrolled ( 78 % were male , 70 % were black , and the median age was 47 years ) . By 24 weeks , LDL cholesterol levels had decreased in the statin group , compared with an increase in the placebo group ( -28 % vs + 3.8 % ; P < .01 ) . A 10 % reduction in the lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) level was seen in the statin group , compared with a 2 % reduction in the placebo group ( P < .01 ) . In multivariable regression , receipt of statin treatment and having a nadir CD4(+ ) T-cell count of ≤100 cell/µL were the only statistically significant predictors of a decrease in Lp-PLA2 level . Markers of systemic inflammation did not change significantly between groups . CONCLUSIONS Twenty-four weeks of rosuvastatin therapy significantly decreased the level of Lp-PLA2 , a vascular-specific , inflammatory enzyme that predicts cardiovascular events in the general population . Statins may hold promise as a means of attenuating CVD risk in HIV-infected individuals by decreasing Lp-PLA2 levels Regular consumption of flavonoids may reduce the risk for CVD . However , the effects of individual flavonoids , for example , quercetin , remain unclear . The present study was undertaken to examine the effects of quercetin supplementation on blood pressure , lipid metabolism , markers of oxidative stress , inflammation , and body composition in an at-risk population of ninety-three overweight or obese subjects aged 25 - 65 years with metabolic syndrome traits . Subjects were r and omised to receive 150 mg quercetin/d in a double-blinded , placebo-controlled cross-over trial with 6-week treatment periods separated by a 5-week washout period . Mean fasting plasma quercetin concentrations increased from 71 to 269 nmol/l ( P < 0.001 ) during quercetin treatment . In contrast to placebo , quercetin decreased systolic blood pressure ( SBP ) by 2.6 mmHg ( P < 0.01 ) in the entire study group , by 2.9 mmHg ( P < 0.01 ) in the subgroup of hypertensive subjects and by 3.7 mmHg ( P < 0.001 ) in the subgroup of younger adults aged 25 - 50 years . Quercetin decreased serum HDL-cholesterol concentrations ( P < 0.001 ) , while total cholesterol , TAG and the LDL : HDL-cholesterol and TAG : HDL-cholesterol ratios were unaltered . Quercetin significantly decreased plasma concentrations of atherogenic oxidised LDL , but did not affect TNF-alpha and C-reactive protein when compared with placebo . Quercetin supplementation had no effects on nutritional status . Blood parameters of liver and kidney function , haematology and serum electrolytes did not reveal any adverse effects of quercetin . In conclusion , quercetin reduced SBP and plasma oxidised LDL concentrations in overweight subjects with a high-CVD risk phenotype . Our findings provide further evidence that quercetin may provide protection against CVD Background Raisins are a significant source of dietary fiber and polyphenols , which may reduce cardiovascular disease ( CVD ) risk by affecting lipoprotein metabolism and inflammation . Walking represents a low intensity exercise intervention that may also reduce CVD risk . The purpose of this study was to determine the effects of consuming raisins , increasing steps walked , or a combination of these interventions on blood pressure , plasma lipids , glucose , insulin and inflammatory cytokines . Results Thirty-four men and postmenopausal women were matched for weight and gender and r and omly assigned to consume 1 cup raisins/d ( RAISIN ) , increase the amount of steps walked/d ( WALK ) or a combination of both interventions ( RAISINS + WALK ) . The subjects completed a 2 wk run-in period , followed by a 6 wk intervention . Systolic blood pressure was reduced for all subjects ( P = 0.008 ) . Plasma total cholesterol was decreased by 9.4 % for all subjects ( P < 0.005 ) , which was explained by a 13.7 % reduction in plasma LDL cholesterol ( LDL-C ) ( P < 0.001 ) . Plasma triglycerides ( TG ) concentrations were decreased by 19.5 % for WALK ( P < 0.05 for group effect ) . Plasma TNF-α was decreased from 3.5 ng/L to 2.1 ng/L for RAISIN ( P < 0.025 for time and group × time effect ) . All subjects had a reduction in plasma sICAM-1 ( P < 0.01 ) . Conclusion This research shows that simple lifestyle modifications such as adding raisins to the diet or increasing steps walked have distinct beneficial effects on CVD risk BACKGROUND Triclosan toothpaste is effective in controlling plaque and gingivitis and slowing progression of periodontitis ; however , its influence on inflammatory biomarkers of cardiovascular disease ( CVD ) , as well as on kidney and liver function , is unknown . METHODS Patients recruited from the Cardiovascular Unit at Prince Charles Hospital , Brisbane , Australia , were r and omized to triclosan ( n = 193 ) or placebo ( n = 190 ) groups and assessed for total cholesterol ( TC ) , high density lipoprotein ( HDL ) and low density lipoprotein ( LDL ) cholesterol , triglycerides , C-reactive protein , erythrocyte sedimentation rate ( ESR ) , hemoglobin , total white cell count ( WCC ) , estimated glomerular filtration rate ( eGFR ) , and liver function enzymes , annually for 5 years . A st and ard mixed model for each marker included group , sex , age , hypertension , diabetes , periodontal status , statin and anti-inflammatory drug use , and smoking as covariates . Changes in eGFR , WCC , and ESR were further analyzed using transition modeling . RESULTS Triclosan toothpaste led to a greater decrease in TC ( P = 0.03 ) , LDL cholesterol ( P = 0.04 ) , and HDL cholesterol ( P = 0.05 ) than placebo toothpaste . ESR increased at a slower rate in the triclosan group ( P ≈ 0.06 ) and was less likely to increase and more likely to improve in males on statins but not anti-inflammatory drugs in the triclosan group versus the placebo group . Markov modeling of the binary response for eGFR ( greater than or less than/equal to the baseline median value ) showed that patients with diabetes in the placebo group were significantly ( P ≈ 0.05 ) more likely to deteriorate than either patients with diabetes in the triclosan group or patients without diabetes in each group . CONCLUSIONS These data suggest that triclosan toothpaste may influence some inflammatory biomarkers of CVD , but not kidney or liver function . However , it is unclear if this influence is clinical ly significant Aims The aims of the study were , first , to critically evaluate lipoprotein(a ) [ Lp(a ) ] as a cardiovascular risk factor and , second , to advise on screening for elevated plasma Lp(a ) , on desirable levels , and on therapeutic strategies . Methods and results The robust and specific association between elevated Lp(a ) levels and increased cardiovascular disease (CVD)/coronary heart disease ( CHD ) risk , together with recent genetic findings , indicates that elevated Lp(a ) , like elevated LDL-cholesterol , is causally related to premature CVD/CHD . The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels . Mechanistically , elevated Lp(a ) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a ) resembles both plasminogen and plasmin but has no fibrinolytic activity , or may accelerate atherosclerosis because , like LDL , the Lp(a ) particle is cholesterol-rich , or both . We advise that Lp(a ) be measured once , using an isoform-insensitive assay , in subjects at intermediate or high CVD/CHD risk with premature CVD , familial hypercholesterolaemia , a family history of premature CVD and /or elevated Lp(a ) , recurrent CVD despite statin treatment , ≥3 % 10-year risk of fatal CVD according to European guidelines , and /or ≥10 % 10-year risk of fatal + non-fatal CHD according to US guidelines . As a secondary priority after LDL-cholesterol reduction , we recommend a desirable level for Lp(a ) < 80th percentile ( less than ∼50 mg/dL ) . Treatment should primarily be niacin 1–3 g/day , as a meta- analysis of r and omized , controlled intervention trials demonstrates reduced CVD  by niacin treatment . In extreme cases , LDL-apheresis is efficacious in removing Lp(a ) . Conclusion We recommend screening for elevated Lp(a ) in those at intermediate or high CVD/CHD risk , a desirable level < 50 mg/dL as a function of global cardiovascular risk , and use of niacin for Lp(a ) and CVD/CHD risk reduction INTRODUCTION The biological mechanisms through which increased physical activity or structured exercise training lowers the risk of recurrent cardiac events are incompletely understood . We examined the extent to which modification of primary risk markers explains the association between physical activity and cardiovascular death in participants with diagnosed cardiovascular disease ( CVD ) . METHODS AND RESULTS In a prospect i ve study of 1429 participants with physician-diagnosed CVD living in Engl and and Scotl and ( age = 66.5 ± 11.1 yr ( mean ± SD ) , 54.2 % men ) , we measured physical activity and several risk markers ( body mass index , total-to-HDL cholesterol ratio , diagnosed diabetes , systolic blood pressure , resting heart rate , C-reactive protein ) at baseline . The main outcome was CVD death . There were a total of 446 all-cause deaths during an average of 7.0 ± 3.1 yr of follow-up , of which 213 were attributed to cardiovascular causes . Participation in moderate to vigorous physical activity at least three sessions per week was associated with lower risk of CVD death ( hazard ratio = 0.61 , 95 % confidence interval = 0.38 - 0.98 ) . Physically active participants demonstrated significantly lower levels of body mass index , diabetes , and inflammatory risk ( C-reactive protein ) . Metabolic ( body mass index , total-to-HDL cholesterol ratio , and physician-diagnosed diabetes ) and inflammatory risk factors explained an estimated 12.8 % and 15.4 % , respectively , of the association between physical activity and CVD death . CONCLUSIONS Physical activity may reduce the risk of secondary CVD events , in part , by improving metabolic and inflammatory risk markers Consumption of industrial trans fatty acids ( iTFA ) increases LDL cholesterol , decreases HDL cholesterol , and is strongly associated with a higher risk of cardiovascular disease ( CVD ) . However , changes in circulating cholesterol can not explain the entire effect . Therefore , we studied whether iTFA and conjugated linoleic acid ( CLA ) affect markers of inflammation and oxidative stress .  Sixty-one healthy adults consumed each of 3 diets for 3 wk , in r and om order . Diets were identical except for 7 % of energy provided by oleic acid ( control diet ) , iTFA , or CLA . At the end of the 3 wk , we measured plasma inflammatory markers IL-6 , C-reactive protein , tumor necrosis factor receptors I and II ( TNF-RI and -RII ) , monocyte chemotactic protein-1 and E-selectin , and urinary 8-iso-PGF(2α ) , a marker of lipid peroxidation . Consumption of iTFA caused 4 % lower TNF-RI concentrations and 6 % higher E-selectin concentrations compared with oleic acid ( control ) and had no significant effect on other inflammatory markers . CLA did not significantly affect inflammatory markers . The urine concentration of 8-iso-PGF(2α ) [ geometric mean ( 95 % CI ) ] was greater after the iTFA [ 0.54 ( 0.48 , 0.60 ) nmol/mmol creatinine ] and the CLA [ 1.2 ( 1.1 , 1.3 ) nmol/mmol creatinine ] diet periods than after the control period [ 0.45 ( 0.41 , 0.50 ) nmol/mmol creatinine ; P < 0.05 ] . In conclusion , high intakes of iTFA and CLA did not substantially affect plasma concentrations of inflammatory markers , but they increased the urine 8-iso-PGF(2α ) concentration . However , it is unlikely this plays a major role in the mechanism by which iTFA increase the risk of CVD . However , more research is needed to fully underst and the implication s of these findings In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1  The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These BACKGROUND Eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , the primary omega-3 fatty acids in fish oil , have been shown to reduce cardiovascular disease ( CVD ) risk . OBJECTIVE This study aim ed to examine the independent effects of EPA and DHA on lipid and apolipoprotein levels , as well as on inflammatory biomarkers of CVD risk , using doses often used in the general population . DESIGN A blinded , r and omized 6-week trial was performed in 121 healthy , normolipidemic subjects who received olive oil placebo 6g/d , EPA 600mg/d , EPA 1800mg/d , or DHA 600mg/d .  The EPA was derived from genetically modified yeast . RESULTS The subjects tolerated the supplements well with no safety issues ; and the expected treatment-specific increases in plasma EPA and DHA levels were observed . Compared to placebo , the DHA group had significant decreases in postpr and ial triglyceride ( TG ) concentrations ( -20 % , -52.2mg/dL , P=0.03 ) , significant increases in fasting and postpr and ial low-density lipoprotein cholesterol ( LDL-C ) ( + 18.4 % , 17.1mg/dL , P=0.001 ) , with no significant changes in inflammatory biomarkers . No significant effects were observed in the EPA 600mg/d group . The high-dose EPA group had significant decreases in lipoprotein-associated phospholipase A2 concentrations ( Lp-PLA2 ) ( -14.1 % , -21.4ng/mL , P=0.003 ) . CONCLUSIONS The beneficial effects of EPA 1800mg/d on CVD risk reduction may relate in part to the lowering of Lp-PLA2 without adversely affecting LDL-C. In contrast , DHA decreased postpr and ial TG , but raised LDL-C. Our observations indicate that these dietary fatty acids have divergent effects on cardiovascular risk markers No indices are currently available to facilitate clinicians to identify patients who need either statin monotherapy or statin-ezetimibe combined treatment . We aim ed to investigate whether cholesterol synthesis and absorption markers can predict the cholesterol-lowering response to statin . Total 306 statin-naïve patients with high risk of coronary heart disease ( CHD ) were treated with atorvastatin 20 mg/day for 1 month . Cholesterol synthesis and absorption markers and LDL cholesterol ( LDL-C ) levels were measured before and after treatment . Atorvastatin decreased LDL-C by 36.8 % ( range : decrease of 74.5 % to increase of 31.9 % ) . Baseline cholesterol synthesis marker lathosterol and cholesterol absorption marker campesterol codetermined the effect of atorvastatin treatment . The effect of cholesterol lowering by atorvastatin was significantly associated with baseline lathosterol levels but modified bidirectionally by baseline campesterol levels . In patients with the highest baseline campesterol levels , atorvastatin treatment decreased cholesterol absorption by 46.1 % , which enhanced the effect of LDL-C lowering . Atorvastatin treatment increased cholesterol absorption by 52.3 % in those with the lowest baseline campesterol levels , which attenuated the effect of LDL-C reduction . Especially those with the highest lathosterol but the lowest campesterol levels at baseline had significantly less LDL-C reduction than those with the same baseline lathosterol levels but the highest campesterol levels ( 27.3 % versus 42.4 % , P = 0.002 ) . These results suggest that combined patterns of cholesterol synthesis /absorption markers , rather than each single marker , are potential predictors of the LDL-C-lowering effects of atorvastatin in high-risk CHD patients Our purpose was to evaluate associations of single nucleotide polymorphisms ( SNPs ) at the low density lipoprotein ( LDL ) receptor ( LDLR C44857 T , minor allele frequency ( MAF ) 0.26 , and A44964 G , MAF 0.25 , both in the untranslated region ) and HMG-CoA reductase ( HMGCR i18 T > G , MAF 0.019 ) gene loci with baseline lipid values , statin-induced LDL-cholesterol ( C ) lowering response , and incident coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) on trial . Our population consisted of 5804 elderly men and women with vascular disease or one or more vascular disease risk factors , who were r and omly allocated to pravastatin or placebo .  Other risk factors and apolipoprotein ( apo ) E phenotype were controlled for in the analysis . Despite a prior report , no relationships with the HMGCR SNP were noted . For the LDLR SNPs C44857 T and A44964 G we noted significant associations of the rare alleles with baseline LDL-C and triglyceride levels , a modest association of the C44857 T with LDL-C lowering to pravastatin in men , and significant associations with incident CHD and CVD of both SNPs , especially in men on pravastatin . Our data indicate that genetic variation at the LDLR locus can affect baseline lipids , response to pravastatin , and CVD risk in subjects placed on statin treatment OBJECTIVE The aim of the present study was to investigate the associations of cumulative inflammatory burden ( assessed by serial measurements of inflammatory markers ) and classical cardiovascular disease ( CVD ) risk factors with  asymmetric dimethylarginine ( ADMA )  in a large prospect i ve cohort of patients with established RA . METHODS Two hundred and one RA patients [ 155 females , median age 67 years ( range 59 - 73 ) ] were assessed at baseline ( 2006 ) for the presence of classical CVD risk factors and determination of systemic inflammation by CRP and ESR . Global CVD risk was identified by the Framingham Risk Score and the Reynolds Risk Score . At follow-up ( 2012 ) ,  ADMA levels were measured by ELISA . A quarterly measurement of CRP and ESR for each year the patient was in the study was used to produce an average area under the curve ( AAUC ) for ESR and CRP . RESULTS Regression analysis revealed that baseline ESR in 2006 and the AAUC of ESR and CRP all had significant positive relationships with current ADMA ( P = 0.004 , P < 0.001 and P = 0.002 , respectively ) . Baseline CRP in 2006 was not a significant predictor of ADMA ( P = 0.093 ) , although this relationship was in the same direction as the other factors . These results remained consistent after adjustment for classical CVD risk factors . CONCLUSION Cumulative inflammatory burden is positively associated with  ADMA levels , suggesting a potential pathogenic mechanism through which chronic systemic inflammation exerts deleterious effects on nitric oxide metabolism and endothelial homeostasis . This association is independent of classical CVD risk factors BACKGROUND Statins are prescribed for patients with cardiovascular disease ( CVD ) , along with the recommendation of adopting healthy diets . We evaluated the independent and the combined effect of statins and Mediterranean diet ( MD ) towards mortality risk in patients with previous CVD by using real-life data from a population -based prospect i ve cohort . METHODS Longitudinal analysis on 1180 subjects ( mean age 67.7 ± 10 ) with prior CVD at enrollment in the Moli-sani Study and followed up for 7.9 y ( median ) .  Adherence to MD was appraised by a Mediterranean diet score .  Hazard ratios ( HR ) with 95 % confidence intervals ( 95 % CI ) were calculated by multivariable Cox regression and competing risk models . RESULTS Multivariable risk estimates associated with a 2-point increase in MD score were 0.84 ( 95 % CI 0.70 - 1.00 ) , 0.77 ( 0.61 - 0.97 ) and 0.70 ( 0.52 - 0.93 ) for overall , cardiovascular and coronary artery disease (CAD)/cerebrovascular deaths , respectively  . Statins were not associated with death risk . Subjects combining statins and average-high adherence to MD had much lower than expected risk of cardiovascular and CAD/cerebrovascular mortality ( p for interaction = 0.045 and 0.0015 , respectively ) as compared to those neither using statins nor having average-high MD . The combination of average-high MD and statins was associated in a likely synergistic way with reduced low- grade inflammation , but not with blood cholesterol . CONCLUSIONS MD lowered the risk of all-cause , cardiovascular and CAD/cerebrovascular mortality CVD patients , net of statins . In the same population , statins  reduced CVD death risk only in combination with MD . Low- grade inflammation , rather than lipids , is likely to be on the pathway of the interaction between MD and statins towards mortality risk Aims A r and omized , double-blind , placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen , an apolipoprotein B-100 ( apoB ) synthesis inhibitor , in patients who are statin intolerant and at high risk for cardiovascular disease ( CVD ) . Methods and results Thirty-three subjects , not receiving statin therapy because of statin intolerance , received a weekly subcutaneous dose of 200 mg mipomersen or placebo ( 2:1 r and omization ) for 26 weeks . The primary endpoint was per cent change in LDL cholesterol ( LDL-c ) from the baseline to Week 28 . The other efficacy endpoints were per cent change in apoB and lipoprotein a [ Lp(a ) ] . Safety was determined using the incidence of treatment-emergent adverse events ( AEs ) and clinical laboratory evaluations . After 26 weeks of mipomersen  administration , LDL-c was reduced by 47 ± 18 % ( P < 0.001 vs. placebo ) . apoB and Lp(a ) were also significantly reduced by 46 and 27 % , respectively ( P < 0.001 vs. placebo ) . Four mipomersen ( 19 % ) and two placebo subjects ( 17 % ) discontinued dosing prematurely due to AEs . Persistent liver transaminase increases ≥3 × the upper limit of normal were observed in seven ( 33 % ) subjects assigned to mipomersen . In selected subjects , liver fat content was assessed , during and after treatment , using magnetic resonance spectroscopy . Liver fat content in these patients ranged from 0.8 to 47.3 % . Liver needle biopsy was performed in two of these subjects , confirming hepatic steatosis with minimal inflammation or fibrosis . Conclusion The present data suggest that mipomersen is a potential therapeutic option in statin-intolerant patients at high risk for CVD . The long-term follow-up of liver safety is required . Clinical Trial Registration : Clinical Trials.gov identifier : Background GlycA , a novel protein glycan biomarker of N‐acetyl side chains of acute‐phase proteins , was recently associated with incident cardiovascular disease ( CVD ) in healthy women . Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown . Methods and Results In the Justfication for the Use of Statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) trial ( NCT00239681 ) , participants with low‐density lipoprotein cholesterol < 130 mg/dL and high‐sensitivity C‐reactive protein ( hsCRP ) ≥2 mg/L were r and omized to rosuvastatin 20 mg/day or placebo . GlycA was quantified by nuclear magnetic resonance spectroscopy in 12 527 before r and omization and 10 039 participants at 1 year . A total of 310 first primary CVD events occurred during maximum follow‐up of 5.0 years ( median , 1.9 ) . GlycA changed minimally after 1 year on study treatment : 6.8 % and 4.7 % decrease in the rosuvastatin and placebo groups , respectively . Overall , baseline GlycA levels were associated with increased risk of CVD : multivariable‐adjusted hazard ratio ( HR ) per SD increment , 1.20 ( 95 % CI , 1.08–1.34 ; P=0.0006 ) . After additionally adjusting for hsCRP , this was slightly attenuated ( HR , 1.18 ; 95 % CI , 1.04–1.35 ; P=0.01 ) . On‐treatment GlycA levels were also associated with CVD ; corresponding multivariable‐adjusted HRs per SD before and after additionally adjusting for hsCRP : 1.27 ( 95 % CI , 1.13–1.42 ; P<0.0001 ) and 1.24 ( 95 % CI , 1.07–1.44 ; P=0.004 ) , respectively . Tests for heterogeneity by treatment arm were not significant ( P for interaction , > 0.20 ) . Conclusion In the JUPITER trial , increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP . Clinical Trials Registration URL : http://www . clinical trials.gov . Unique identifier : NCT00239681 Objective : To evaluate associations between traditional cardiovascular disease ( CVD ) risk factors , inflammatory markers and markers of HIV disease activity with ultrasonographic measures of CVD risk in patients with HIV who are not receiving antiretroviral therapy ( ART ) . Design : Cross-sectional , baseline evaluation of ART-naive HIV-infected individuals without known CVD or diabetes mellitus enrolled in a r and omized ART treatment trial . Methods : Prior to ART initiation ,  carotid artery intima – media thickness ( CIMT ) and brachial artery flow-mediated dilation ( FMD ) were measured . Additional parameters included CD4 cell count , HIV viral load , body composition , lipoproteins and inflammatory markers . Associations with common CIMT , bifurcation CIMT , presence of carotid artery lesions and brachial artery FMD were evaluated . Results : The 331 enrolled individuals were a median ( first – third quartile ) of 36 ( 28–45 ) years old .  Common and bifurcation CIMT values were higher and lesions more prevalent with older age ( P < 0.001 ) . FMD was lower with older age ( P = 0.009 ) . Those with a Framingham Risk Score of at least 6 % per 10 years ( N = 44 ) had higher common and bifurcation CIMT ( P < 0.001 ) , carotid lesion prevalence ( P < 0.001 ) and lower FMD ( P = 0.035 ) . Independent associations with common CIMT were identified for increasing age , height , weight , small low-density lipoprotein ( LDL ) particles and black race ; these were similar for bifurcation CIMT . Presence of carotid artery lesions was associated with increasing age , presence of metabolic syndrome , interleukin-6 and lower HIV-1 RNA . Conclusion : In a contemporary cohort of ART-naive HIV-infected individuals , ultrasonographic measures of CVD risk were more strongly associated with traditional risk factors than CD4 cell counts , HIV replication or inflammatory markers BACKGROUND Observational data suggest that low 25-hyroxyvitamin D is associated with cardiovascular disease ( CVD ) and its risk factors include diabetes , metabolic syndrome , insulin resistance , hypertension , microalbuminuria and inflammation . We examined the differences between risk factors of CVD before and after treatment with calcitriol in type 2 diabetic patients with vitamin D deficiency . METHODS This study was a clinical trial consisting of 119 type 2 diabetic patients . Forty three patients had vitamin D insufficiency ( 25 OH D less than 30 ng/dl ) who underwent calcitriol treatment  with 0.5 microgram per day for 8 weeks . Blood pressure , fasting blood sugar ( FBS ) , glycosylated hemoglobin ( HbA1C ) , lipid profile , high sensitive C-reactive protein ( HsCRP ) , Homocysteine and albumin to creatinine ratio were measured , before and after the treatment period . Then the two sets of results were compared with each other . RESULTS Following treatment with  calcitriol HbA1C , total cholesterol , low density lipoprotein(LDL ) , high density lipoprotein(HDL ) and diastolic blood pressure decreased significantly ( p = 0.01 , 0.01 , 0.04 , 0.001 and 0.04 respectively ) but the changes in other parameters were not significant . CONCLUSION Replacement of vitamin D may have a beneficial effect on some of the risk factors of CVD in diabetic patients Increased intake of marine long-chain n-3 PUFA ( n-3 LCPUFA ) may decrease the risk of CVD and reduce mortality by lowering serum TAG and blood pressure ( BP ) . Furthermore , n-3 LCPUFA may affect novel CVD risk markers related to inflammation and vascular function . The objective of the present study was to examine the effect of farmed trout on novel and traditional CVD risk markers in healthy men , and to evaluate whether this was affected by the aquacultural feed regime . We performed a parallel , 8-week intervention study in which sixty-eight healthy male volunteers were r and omised to consume either a daily meal with 150 g farmed trout raised on either marine or vegetable-based feed , or a reference meal containing 150 g chicken . Twenty-four hour BP , pulse wave velocity , augmentation index , fatty acid composition of erythrocyte ( RBC ) , and concentrations of TAG , HDL-cholesterol , LDL-cholesterol , glucose , insulin , C-reactive protein ( CRP ) and other markers of inflammation were measured at weeks 0 and 8 . RBC content of total n-3 LCPUFA , both EPA and DHA , was significantly higher among men consuming trout raised on marine feed compared with men consuming the  vegetable-fed trout or chicken . The three intervention groups did not differ significantly with respect to any of the other outcome variables , although there were trends towards associations between the changes in RBC n-3 LCPUFA and those in BP and CRP . In the present study , we conclude that we could not confirm the fish oil-induced reduction in CVD risk markers after daily consumption of trout with high or low n-3 LCPUFA content . However , trout raised on vegetable-based feed had less pronounced impact on RBC n-3 LCPUFA status OBJECTIVE The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance ( IGT ) . Participants with IGT are at high risk for cardiovascular disease ( CVD ) , with a marked increase in the number and severity of CVD risk factors . We prospect ively assessed the impact of our interventions on hypertension , dyslipidemia , and CVD events . RESEARCH DESIGN AND METHODS The study group consisted of 3,234 individuals with IGT r and omly assigned to receive intensive lifestyle intervention , metformin , or placebo . Annual assessment of blood pressure , lipids , electrocardiogram , and CVD events was undertaken . RESULTS Hypertension was present in 30 % of participants at study entry and then increased in the placebo and metformin groups , although it significantly decreased with intensive lifestyle intervention . Triglyceride levels fell in all treatment groups , but fell significantly more with intensive lifestyle intervention . Total cholesterol and LDL cholesterol levels were similar among treatment groups . Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up , the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27 - 28 % less for hypertension and 25 % less for hyperlipidemia compared with placebo and metformin groups . Over an average of 3 years , 89 CVD events from 64 participants were positively adjudicated study wide , with no differences among treatment groups . CONCLUSIONS Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy . Although no differences in CVD events were noted after 3 years , achieved risk factor modifications suggest that longer intervention may reduce CVD event rates OBJECTIVES To examine markers of inflammation in 9- and 15-year-olds with high waist circumference and compare these with controls , and to examine the relationships between inflammatory markers and cardiovascular disease ( CVD ) risk factors . METHODS Cross-sectional analysis of data from 2 299 Norwegian 9- and 15-year-olds participating in the " Physical activity among Norwegian Children Study " . In each sex and age group , the 10 participants with the highest waist circumference ( HW ) were selected ( n=40 ) for analyses , and a r and om sample of 40 participants within the same groups were included as controls . Inflammatory markers included C-reactive protein ( CRP ) , leptin , adiponectin , plasminogen activator inhibitor-1 ( PAI-1 ) , tumor necrosis factor-alpha ( TNF-alpha ) , hepatocyte growth factor ( HGF ) , resistin and interleukin-6 ( IL-6 ) . The CVD risk factors included blood pressure , glucose , insulin , triglycerides and high density lipoprotein cholesterol . RESULTS HW participants had elevated levels of CRP ( mean difference 1.50 mg/l ; 95 % confidence interval [ CI ] 0.33 to 2.66 ) , PAI-1 ( mean difference 13.3 ng/ml ; 95 % CI 4.1 to 22.5 ) and HGF ( mean difference 0.29 ng/ml ; 95 % CI 0.07 to 0.51 ) compared with controls . All CVD risk factors differed between the HW group and controls . The CVD risk factors were not associated with TNFalpha or IL-6 , but CRP , HGF and PAI-1 were related to the metabolic risk score . CONCLUSIONS Low grade systemic inflammation is already present in youth with high waist circumference . CRP , HGF and PAI-1 may be related to the adverse overall metabolic risk profile observed in these children and adolescents OBJECTIVE The purpose of this study was to examine differences in cardiovascular disease ( CVD ) risk factors across four cross-tabulated groups of cardiorespiratory fitness and body mass index in 8- to 18-year-old children and adolescents . METHODS The sample included 296 boys and 188 girls ( mean age=15.7 years ) participating in the Aerobics Center Longitudinal Study . Participants were cross tabulated into four groups using a median split of age-adjusted treadmill time to exhaustion ( TM ) and body mass index ( BMI ) . Group differences in CVD risk factors ( blood pressure [ BP ] , fasting total cholesterol [ TC ] , low density lipoprotein-cholesterol [ LDL-C ] , high density lipoprotein-cholesterol [ HDL-C ] , TC : HDL-C , triglycerides [ TG ] , glucose , and a metabolic syndrome score ) were examined by ANCOVA , controlling for age . RESULTS In males , significant differences across groups were observed for systolic BP , mean arterial pressure ( MAP ) , TC , LDL-C , TC : HDL-C and the metabolic syndrome score ( p<0.05 ) . In females , only TG was significantly different across groups ( p<0.05 ) . A trend for significance was also observed for DBP and TG in males ( p=0.09 to 0.11 ) and diastolic BP , MAP , HDL-C , and the metabolic syndrome score in females ( p=0.14 to 0.16 ) . In general , males and females in the low BMI group , either fit or unfit , had lower BP and blood lipid values than those in the high BMI group . In both sexes , the high BMI /low fit group had the highest ( most adverse ) metabolic syndrome score . CONCLUSION This study utilized a unique approach to examine the possible interaction of fitness and fatness on CVD risk factors in children and adolescents . The results provide some evidence for the consideration of both variables when interpreting CVD risk factors in young people BACKGROUND New dietary strategies to reduce cardiovascular disease ( CVD ) risk include the addition of fiber to the diet . The effect of soluble-fiber consumption derived from Plantago ovata husk on lipid risk factors in patients with CVD is unknown . OBJECTIVE We compared the effects of soluble fiber ( P. ovata husk ) with those of insoluble fiber ( P. ovata seeds ) on plasma lipid , lipoprotein , and apolipoprotein ( apo ) concentrations within a CVD secondary prevention program . DESIGN In a r and omized , crossover , controlled , single-blind design , 28 men with CVD ( myocardial infa rct ion or stable angina ) and an LDL-cholesterol concentration < /=3.35 mmol/L consumed for 8 wk , under controlled conditions , a low-saturated-fat diet supplemented with 10.5 g P. ovata husk/d or 10.5 g P. ovata seeds/d . Fasting plasma lipid concentrations and polymorphisms of genes involved in lipid metabolism , such as apo A-IV , apo E , and fatty acid-binding protein , were measured . RESULTS Plasma triacylglycerol decreased ( 6.7 % ; P < 0.02 ) , the ratio of apo B 100 to apo A-I decreased ( 4.7 % ; P < 0.02 ) , and apo A-I increased ( 4.3 % ; P < 0.01 ) in the P. ovata husk consumers . Compared with the intake of insoluble fiber , the intake of P. ovata husk increased HDL-cholesterol concentrations by 6.7 % ( P = 0.006 ) and decreased the ratio of total to HDL cholesterol and of LDL to HDL cholesterol by 10.6 % ( P = 0.002 ) and 14.2 % ( P = 0.003 ) , respectively . CONCLUSION In the secondary prevention of CVD , P. ovata husk intake induces a more beneficial effect on the cardiovascular lipid risk-factor profile than does an equivalent intake of insoluble fiber OBJECTIVE To examine the effect of intensive lipid-lowering therapy on a composite cardiovascular outcome ( cardiovascular disease [ CVD ] ) , consisting of mortality and morbidity end points , in patients with inflammatory joint disease ( rheumatoid arthritis [ RA ] , ankylosing spondylitis [ AS ] , or psoriatic arthritis [ PsA ] ) by post hoc analysis of 2 prospect i ve trials of statins with a secondary end point of CVD outcome ( the Treating to New Targets [ TNT ] and Incremental Decrease in End Points Through Aggressive Lipid Lowering [ IDEAL ] studies ) . METHODS Of the 18,889 patients participating in the 2 trials , 199 had RA , 46 had AS , and 35 had PsA.  Lipid-lowering therapy consisted of an intensive regimen of atorvastatin 80 mg or a conventional/low-dose regimen of atorvastatin 10 mg or simvastatin 20 - 40 mg . The median duration of followup was nearly 5 years . Changes in lipid levels were examined by analyses of covariance . The effect on CVD was examined by Cox regression analyses , and heterogeneity tests were performed . RESULTS Patients with RA and those with AS had lower baseline cholesterol levels than patients without inflammatory joint disease ( least squares mean ± SEM 180.7 ± 2.3 mg/dl and 176.5 ± 4.7 mg/dl , respectively , versus 185.6 ± 0.2 mg/dl ; P = 0.03 and P = 0.05 , respectively ) . Statin treatment led to a comparable decrease in lipid levels and a 20 % reduction in overall risk of CVD in both patients with and those without inflammatory joint disease . CONCLUSION Our findings indicate that patients with and those without inflammatory joint disease experience comparable lipid-lowering effects and CVD risk reduction after intensive treatment with statins
Our meta‐ analysis showed beneficial effects  of statin use  on reducing inflammatory markers in patients with MetS and related disorders
& NA ; Current evidence suggests that statin use decreases the incidence of cardiovascular diseases ( CVD ) through reducing LDL cholesterol and decreasing inflammation .
Metabolic syndrome ( MetS ) is usually associated with increased inflammatory markers and increased risk of CVD .