Relation of Clinical Benefit of Raising High-Density Lipoprotein Cholesterol to Serum Levels of Low-Density Lipoprotein Cholesterol in Patients With Coronary Heart Disease (from the Bezafibrate Infarction Prevention Trial)

Low high-density lipoprotein (HDL) cholesterol is a strong independent predictor of cardiovascular risk. The present study was designed to assess the relation between the clinical response to HDL cholesterol modification and serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary artery disease (CAD). The risk for a major cardiac event (defined as nonfatal myocardial infarction or cardiac death) during a median 7.9-year follow-up period in 3,020 patients with CAD enrolled in the Bezafibrate Infarction Prevention (BIP) trial was related to changes in lipid levels during the study. Baseline LDL cholesterol levels were categorized according to National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariate analysis demonstrated that the benefit of HDL cholesterol increase was most pronounced in patients with low baseline LDL cholesterol (≤129 mg/dl; 29% risk reduction per 5 mg/dl increment in HDL cholesterol, p = 0.02), intermediate in patients with intermediate LDL cholesterol (130 to 159 mg/dl; 13% risk reduction per 5 mg/dl increment in HDL cholesterol, p = 0.03), and nonsignificant in patients with high LDL cholesterol (≥160 mg/dl; hazard ratio 0.94, 95% confidence interval 0.75 to 1.17, p = 0.14). A similar relation was shown for risk reduction-associated triglyceride decrements, whereas the benefit of LDL cholesterol reduction was more pronounced in patients with baseline LDL cholesterol ≥130 mg/dl. In conclusion, these data suggest that the clinical response to HDL cholesterol and triglyceride modification is inversely related to baseline LDL cholesterol levels. Thus, combined assessment of baseline and follow-up lipid levels to direct therapeutic goals in patients with CAD may provide incremental prognostic information to secondary prevention that is based solely on LDL cholesterol modification.