VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial

Background-Plasma triglyceride concentration has been an inconsistent indep endent risk factor for coronary heart disease, perhaps because of the metab olic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. Methods and Results-We conducted a prospective, nested case-control study i n the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-c ontrolled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/d L). Baseline concentrations of VLDL-apolipoprotein (apo) B (the VLDL partic le concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or corona ry death (cases, n=418) with those in patients who did not have a cardiovas cular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholest erol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE i n HDL were all interrelated, and each was a univariate predictor of subsequ ent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P=0.04), apoCIII i n VLDL+LDL (RR 2.3, P=0.04), and apoE in HDL (RR 1.8, P=0.02). Plasma trigl ycerides, a univariate predictor of coronary events (RR 1.6, P=0.03), was n ot 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 pla sma triglycerides perhaps because their known metabolic properties link the m more closely to atherosclerosis.