VLDL, Apolipoproteins B, CIII, and E, and Risk of Recurrent Coronary Events in the Cholesterol and Recurrent Events (CARE) Trial

Abstract

Background —Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. Methods and Results —We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL–apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P =0.04), apoCIII in VLDL+LDL (RR 2.3, P =0.04), and apoE in HDL (RR 1.8, P =0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P =0.03), was not related to coronary events (RR 1.3, P =0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results. Conclusions —The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.