Effect of gemfibrozil on the regulation of HDL subfractions in hypertriglyceridaemic patients.

Abstract

OBJECTIVES: To study changes of HDL subfractions and their regulation during gemfibrozil treatment in hypertriglyceridaemia. DESIGN: Twenty patients with hypertriglyceridaemia were randomized to receive either 1200 mg day-1 gemfibrozil or placebo for 3 months. After a 6-week, single-blind placebo period, the patients were randomized to receive either gemfibrozil or placebo for 3 months in a double-blind study. SETTING: The patients were studied as outpatients in the Third Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. MAIN OUTCOME MEASURES: Ultracentrifugally isolated HDL subclasses; concentrations of apoA-I, apoA-II, LpA-I and LpA-I:A-II particles; post-heparin plasma lipoprotein lipase (LPL), hepatic lipase (HL) and plasma cholesteryl ester transfer protein (CETP) activities; phospholipid transfer protein (PLTP) and lecithine cholesteryl acyltransferase (LCAT) activities were measured in plasma from six patients from both groups. RESULTS: Gemfibrozil increased the concentration of HDL cholesterol (+11.1%) because of the rise of HDL3 cholesterol (34.5%, P < 0.01). The concentration of LpA-I particles was reduced during gemfibrozil treatment (-12.4%, P < 0.05), while that of apoA-II increased (+12.3%, P < 0.01). The LpA-I to LpA-I:A-II ratio decreased significantly in the gemfibrozil group (-18.9%, P < 0.01). Gemfibrozil increased LPL and HL activities by 18.2% (P < 0.05) and by 19.6%, respectively. Plasma CETP activity was also increased during gemfibrozil treatment (+15.8%, P < 0.05). CONCLUSION: The gemfibrozil-induced elevation of HDL3 and apoA-II may reflect the combined action of LPL, HL and CETP on plasma HDL metabolism.