Changes in composition and distribution of LDL subspecies in hypertriglyceridemic and hypercholesterolemic patients during gemfibrozil therapy

Abstract

The effect of gemfibrozil (GEM) on composition and distribution of LDL subspecies in 10 hypertriglyceridemic (HTG) patients with triglyceride (TG) levels of 300–750 mg/dl and low density lipoprotein cholesterol (LDL-C) < 160 mg/dl, and 8 hypercholesterolemic (HC) patients with LDL-C ≥ 190 mg/dl and TG < 200 mg/dl was investigated. Patients were randomized in a double-blind, crossover design to 12 week periods of placebo and 1200 mg/day GEM with an intervening washout period. All 7 LDL subspecies in the density range of 1.029 to 1.063 g/ml in the HTG group contained more TG ( P < 0.01) and less free cholesterol ( P < 0.05, while the proportion of cholesterol ester was lower only in LDL subspecies 1 to 3 ( P < 0.05) as compared to the HC group. In HTG patients, GEM increased the proportion of cholesterol ester ( P < 0.05) in all subfractions, while the proportion of free cholesterol was increased and TG was decreased in LDL subspecies 1 to 4 only ( P < 0.05). GEM decreased the LDL subspecies score from 4.8 ± 0.7 to 4.2 ± 0.5, and the major LDL subclass density from 1.048 ± 0.006 to 1.043 ± 0.002 g/ml ( P < 0.01) in HTG patients. GEM decreased TG levels to mean of 228 ± 52 mg/dl in HTG patients, but there was no change in LDL phenotype. No significant changes in composition and distribution of LDL subspecies were noted in HC patients with GEM. We conclude that GEM significantly altered the composition and distribution of LDL subspecies with a shift from small dense LDL particles to large, less dense particles in HTG patients.