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 (<or=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 (>or=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 >or=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.