on August 25, 2005
Published online before print August 25, 2005, doi: 10.1161/01.ATV.0000183727.90611.4f
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Submitted on February 25, 2005
Accepted on July 28, 2005
Value of High-Density Lipoprotein (HDL) Subpopulations in Predicting Recurrent Cardiovascular Events in the Veterans Affairs HDL Intervention Trial
Bela F. Asztalos *;
From the Lipid Metabolism Laboratory (B.F.A., K.V.H., E.J.S.), HNRCA at Tufts University, Boston, Mass; Department of Veterans Affairs (D.C.), West Haven, Conn; Department of Biostatistics (L.A.C., S.D.), Boston University, Massachusetts; Center for Chronic Disease Outcomes Research (H.E.B.), Veterans Affairs Medical Center, Minneapolis, Minn; and Department of Medicine (S.J.R.), Boston University, Mass.
* To whom correspondence should be addressed. E-mail: bela.asztalos{at}tufts.edu.
Objective--To test the hypothesis whether determination of high-density lipoprotein (HDL) subpopulations provides more power to predict recurrent cardiovascular disease (CVD) events than traditional risk factors in the Veterans Affairs HDL Intervention Trial (VA-HIT).
Methods and Results--Apolipoprotein A-I (apoA-I)-containing HDL subpopulations were quantitatively determined by nondenaturing 2D gel electrophoresis. Hazard ratios of recurrent CVD events were calculated by comparing VA-HIT subjects with (n=398) and without (n=1097) such events. Subjects with new CVD events had significantly lower HDL-C, and apoA-I, and large cholesterol-rich HDL particle (
-1, -2, pre--1, and pre--2) levels, significantly higher triglycerides, and small, poorly lipidated HDL particle (pre-
-1 and -3) levels than subjects without such events. Multivariate analyses indicated that -1 and -2 particle levels were significant negative risk factors, whereas -3 level was a significant positive risk factor for new CVD events. Pre--1 level was a significant risk factor for new CVD event only in univariate analysis. A forward selection model indicated that -1 was the most significant risk factor for recurrent CVD events among HDL particles.
Conclusions--An altered HDL subpopulation profile marked with low -1 and -2 levels and a high -3 level in coronary heart disease patients indicated an elevated risk for new CVD events. Moreover, -1 and -2 levels were superior to HDL-C levels in risk assessment in patients with low HDL-C in VA-HIT.
Key words: HDL subpopulations • apoA-I • HDL-C • CVD risk
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