Bimodal distribution of cholesteryl ester transfer protein activities in normotriglyceridemic men with low HDL cholesterol concentrations

Increased plasma activities of cholesteryl ester transfer protein (CETP) theoretically could lower HDL cholesterol levels due to enhanced transfer of cholesteryl esters from HDL to apo B-containing lipoproteins. To determine whether high CETP activities are associated with isolated hypoalphalipoproteinemia, CETP activities were measured in 109 adult men with HDL cholesterol <35 mg/dL, plasma triglycerides <200 mg/dL, and LDL cholesterol <160 mg/dL; the results were compared with those of 50 normolipidemic (HDL cholesterol >40 mg/dL) male subjects. CETP activities were assayed in vitro and expressed as the percent of [³H]cholesteryl ester transferred from HDL₃ to LDL during a 16-hour incubation. In addition, postheparin plasma activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were determined in 71 patients with a low HDL cholesterol level. Distributions of CETP activities were unimodal in control subjects (mean±SD, 23.1±5.0%), but they were bimodal in the low-HDL patients. Among the latter, 27 patients had elevated CETP activities (40.8±4.6%), whereas 82 patients had CETP activities that overlapped the normal range (26.14±7.6%). Low-HDL patients with normal CETP activities had 20% lower LPL activities (P = .01), 25% higher HTGL activities (P=.03), and 63% lower LPL/HTGL ratios (P<.001) than those of low-HDL patients with increased CETP activity. Furthermore, mean LPL and HTGL activities in the low-HDL patients with elevated CETP activities were in the normal range. Another important distinction between the two subgroups with low HDL was that the subgroup with high CETP activity had only a 30% prevalence of coronary heart disease compared with a 70% prevalence in the subgroup with normal CETP activity (P<.01). These findings suggest that elevated CETP activity may be a significant factor in causing low HDL cholesterol levels in a distinct subgroup of normolipidemic patients with low HDL cholesterol levels.