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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2185.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

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

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.

Correspondence to Bela F. Asztalos, PhD, JM-USDA/HNRCA at Tufts University, Lipid Metabolism Laboratory, 711 Washington St, Boston, MA 02111. 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 (nonfatal myocardial infarction, coronary heart disease death, and stroke) 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, apoA-I, and large cholesterol-rich HDL particle (-1, -2, pre–-1, and pre–-2) levels, significantly higher triglyceride, and small poorly lipidated HDL particle (pre–ß-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–ß-1 level was a significant risk factor for new CVD events 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.

VA-HIT subjects with new CVD events had low HDL-C and apoA-I, large cholesterol-rich HDL particle levels, high TG, and small poorly lipidated HDL particle levels. Low -1 and -2 levels and high -3 levels were independent positive risk factors for recurrent CVD events, -1 and -2 being superior to HDL-C in risk-assessment.

Key Words: HDL subpopulations • apoA-I • HDL-C • CVD risk

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