EFFECTS OF LOWERING ELEVATED LDL CHOLESTEROL ON THE CARDIOVASCULAR RISK OF LIPOPROTEIN(A)

Objective.-To determine if lowering elevated low-density lipoprotein cholesterol (LDL-C) levels offsets the adverse effect of raised lipoprotein(a) (Lp[a]) levels on coronary artery disease (CAD) in men. Design.-Randomized, double-blind, placebo-controlled trial of lipid lowering for CAD. Setting.-Post hoc analysis of the Familial Atherosclerosis Treatment Study. Participants.-A total of 146 men aged 62 years or younger with CAD and apolipoprotein B levels of at least 125 mg/dL. Intervention.-Patients received a Step II Diet and lovastatin (40 mg daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or placebo (plus colestipol if LDL-C >90th percentile) for 2.5 years. They were grouped by their LDL-C responses: ''minimal'' if LDL-C decreased by 10% or less from baseline (mean [SD] change, +6% [13%]) and ''substantial'' if LDL-C decreased more than 10% (mean [SD] change, -40% [16%]). Main Outcome Measure.-Impact of lowering elevated LDL-C on the cardiac event rate (death, myocardial infarction, and revascularization for refractory ischemia) and CAD change associated with elevated Lp(a). Results.-In multivariate analyses, the best correlate of baseline CAD severity was Lp(a) (r=0.30; P<.001). For 36 patients with minimal LDL-C reduction, CAD progression correlated only with in-treatment Lp(a) levels (r=0.45; P<.01), but for 84 patients with substantial LDL-C reduction, disease regressed and its change correlated with in-treatment LDL-C (r=0.24; P<.05) but not with Lp(a) (r=-0.05), Lipoprotein(a) levels were not significantly altered in either group. For 40 patients with Lp(a) at the 90th percentile or higher, events were frequent (39%) if reduction of LDL-C was minimal, but were few (9%) if reduction was substantial (relative risk, 0.23; 95% confidence interval, 0.06 to 0.99). Conclusions.-In men with CAD and elevated LDL-C, Lp(a) levels were dominant correlates of baseline disease severity, its progression, and event rate over 2.5 years, However, with substantial LDL-C reductions, persistent elevations of Lp(a) were no longer atherogenic or clinically threatening. This provides a possible direction for treatment in such patients with elevated Lp(a) and LDL-C.