EFFECT OF GEMFIBROZIL ON THE REGULATION OF HDL SUBFRACTIONS IN HYPERTRIGLYCERIDEMIC PATIENTS

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, s ingle-blind placebo period, the patients were randomized to receive ei ther gemfibrozil or placebo for 3 months in a double-blind study, Sett ing. 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; con centrations of apoA-I, apoA-II, LpA-I and LpA-I:A-II particles; post-h eparin plasma lipoprotein lipase (LPL), hepatic lipase (HL) and plasma cholesteryl ester transfer protein (CETP) activities; phospholipid tr ansfer 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 HDL(3) cholesterol (34.5%, P < 0.01), The concentration of LpA-I particles was reduced during gemfibrozil t reatment (- 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 a nd HL activities by 18.2% (P < 0.05) and by 19.6%, respectively. Plasm a CETP activity was also increased during gemfibrozil treatment (+ 15. 8%, P < 0.05), Conclusion, The gemfibrozil-induced elevation of HDL(3) and apoA-II may reflect the combined action of LPL, HL and CETP on pl asma HDL metabolism.