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

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Abstract
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 (α-1, α-2, pre–α-1, and pre–α-2) levels, significantly higher triglyceride, and small poorly lipidated HDL particle (pre–β-1 and α-3) levels than subjects without such events. Multivariate analyses indicated that α-1 and α-2 particle levels were significant negative risk factors, wherea... 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 α-1 and α-2 levels and high α-3 levels were independent positive risk factors for recurrent CVD events, α-1 and α-2 being superior to HDL-C in risk-assessment.

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