Value of High-Density Lipoprotein (HDL) Subpopulations in Predicting Recurrent Cardiovascular Events in the Veterans Affairs HDL Intervention Trial

Asztalos, Bela F.; Collins, Dorothea; Cupples, L. Adrienne; Demissie, Serkalem; Horvath, Katalin V.; Bloomfield, Hanna E.; Robins, Sander J.; Schaefer, Ernst J.

doi:10.1161/01.atv.0000183727.90611.4f

Cited by 250 publications

(184 citation statements)

References 35 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…(37,38) Differences in distribution and size of HDL-P have been related to CVD risk. (39)(40)(41)(42)(43)(44)(45)(46) Whether there is a unique important protective effect of size of HDL-P measured by NMR spectroscopy requires better assessment of the characteristics and metabolism by size of HDL-P. (39) Large rather than small LDL-P were more strongly related to risk of CHD death for MRFIT men with MetSyn, especially among men without morbid CV events in the first 6 years of the trial. Recent reports from the MESA (36) and the VA-HIT trial (35) have shown that markers of LDL-P rather than size may be a more important determinant of the risk of CHD.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome

et al. 2007

View full text Add to dashboard Cite

We tested the hypotheses whether nuclear magnetic resonance (NMR) determined lipoprotein particles, insulin and adiponectin, and C-reactive protein (CRP) and white blood cell (WBC) count as markers of inflammation predicted risk of coronary heart disease (CHD) death among 428 men age 35-57 years with metabolic syndrome (MetSyn) in a matched case control study within the Multiple Risk Factor Intervention Trial.Blood samples collected at entry into the study and stored at −60° C were obtained from central storage for blood analyte analysis. 214 men with MetSyn who died of CHD were matched with 214 men with MetSyn who did not die of CHD during 18 years of follow-up. Cases were matched to controls on age, study group, number of factors present in the MetSyn, and presence or absence of a non-fatal CVD event during the trial. Mortality follow up was determined using the National Death Index.Higher levels of high density lipoprotein particles (HDL-P), especially medium-sized HDL-P, [hazard ratio (95% confidence interval) 0.45 (0.25-0.83, p<0.01), quartile 1 as compared to quartile 4], were associated with lower risk of CHD death. Low density lipoprotein (LDL) particles were not associated with increased risk of CHD. Elevated LDL cholesterol (LDL-C), smoking and WBC count were, but levels of adiponectin, insulin and CRP were not significantly related to CHD death. In multivariate models adjusting for smoking and LDL-C, medium HDL-P and WBC count remained independent predictors of CHD death.Number of HDL particles, especially medium-sized HDL particles and WBC count were independent predictors of CHD death among men with MetSyn.

show abstract

Section: Discussionmentioning

confidence: 99%

Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Low levels of large HDL particles accompanied by high levels of small HDL particles predicted higher risk of cardiovascular disease events in a recent sub-analysis of the Veterans' Affairs HDL Intervention Trial [11]. HDL subclass distribution during fibrate treatment may thus be clinically interesting.…”

Section: Introductionmentioning

confidence: 99%

Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis Low HDL-cholesterol (HDL-C) is frequently accompanied by high triacylglycerol levels in diabetic dyslipidaemia, increasing the risk of CHD. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, fenofibrate treatment lowered triacylglycerol levels, but the initial 5% increase in HDL-C attenuated over 5 years. We explored the changes in VLDL and HDL subspecies during fenofibrate treatment in a statin-free FIELD cohort. Methods We randomised 171 participants with type 2 diabetes mellitus, who had been recruited to the FIELD study in Helsinki, to micronised fenofibrate (200 mg/day) or placebo in double-blind study design. VLDL and HDL subspecies were separated by ultracentrifugation at baseline and at the second and fifth year. Apolipoprotein (apo)A-I and apoA-II were measured by immunoturbidometric methods and lipoprotein (Lp)A-I and LpAI-AII particles by differential immunoassay. Results Fenofibrate reduced plasma triacylglycerol levels by 26%, resulting from a marked reduction in VLDL1 triacylglycerol (0.62 vs 0.29 mmol/l, p<0.001). Fenofibrate caused an increase in LDL size (Δ0.80 nm, p<0.001). HDL-C was similar between the groups. HDL2-C was decreased by fenofibrate (−27.5% at 5th year, p<0.001) and HDL3-C increased (13.0% at 5th year, p<0.001). Fenofibrate had no effect on apoA-I, whereas apoA-II increased. Thus, LpA-I decreased while LpAI-AII increased. Activities of cholesteryl ester transfer protein, phospholipids transfer protein and lecithin:cholesterylacyl transferase were unchanged by fenofibrate. High homocysteine levels were associated with a slight decrease in HDL-C and apoA-I. Conclusions/interpretation Fenofibrate markedly reduced large VLDL particles and produced a clear shift in HDL subspecies towards smaller particles. The HDL3-C increase in conjunction with unchanged apoA-II levels is a dilemma with regard to cardiovascular disease.

show abstract

“…There is also increasing interest in treating other lipoprotein abnormalities in type 2 diabetes by reducing triacylglycerol [10,11] and/or raising HDL-cholesterol (HDL-C) [12,13]. Fibrate therapy can improve both of these, but there are concerns about combining them with statins because of adverse events [14] and the failure of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial to demonstrate CVD-risk reduction with fenofibrate [15].…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis The aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 (omega-3 EE90; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids) on estimated cardiovascular disease (CVD) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy. Methods A central computer randomised 800 patients in 59 UK general practices to atorvastatin (n=401, 20 mg/day) or placebo (n=399) and omega-3 EE90 (n=397, 2 g/day) or placebo (n=403) in a concealed factorial manner. Participants with LDL-cholesterol <2.6 mmol/l, triacylglycerol <1.5 mmol/l and estimated 10-year CVD risk <20% were compared at 4 months.Results Mean (SD) age was 63.5 (11.7) years, HbA 1c 6.9 (1.1) % and known diabetes duration (median [interquartile range]) was 4 (2-8) years. Fifty-seven per cent were men, 90% white and 74% had an estimated 10-year CVD risk ≥20%. Of 732 patients with 4-month data, more allocated atorvastatin (n=371) compared with placebo (n=361) achieved LDLcholesterol <2.6 mmol/l (91% vs 24%, p<0.001) and had estimated 10-year CVD risks <20% (38% vs 26%, p<0.001). No differences were seen between those allocated omega-3 EE90 (n=371) compared with placebo (n=361) for participants achieving triacylglycerol <1.5 mmol/l (65% vs 60%, p=0.18) or estimated 10-year CVD risks <20% (34% vs 30%, p=0.18). There were no side effects of note. Conclusions/interpretation Many community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies. The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available.

show abstract

Value of High-Density Lipoprotein (HDL) Subpopulations in Predicting Recurrent Cardiovascular Events in the Veterans Affairs HDL Intervention Trial

Cited by 250 publications

References 35 publications

Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome

Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome

Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

Contact Info

Product

Resources

About