EFFECT OF GEMFIBROZIL ON LEVELS OF LIPOPROTEIN[A] IN TYPE-II HYPERLIPOPROTEINEMIC SUBJECTS

Plasma lipoprotein[a] (Lp[a]) levels are highly correlated with angiog raphically demonstrable coronary heart disease, and elevated Lp[a] is an independent risk factor for atherosclerosis. Previous studies have provided evidence that the levels of Lp[a] and triglyceride are relate d, suggesting that Lp[a] might be altered by gemfibrozil, a drug well known for its efficacy in reducing plasma triglycerides. Accordingly, 18 type IIa and 16 type IIb hyperlipoproteinemic males aged 35-58 were treated for 3 months with 600 mg of gemfibrozil twice daily. The effi cacy of the drug in altering lipid and lipoprotein levels was differen t in the two type groups. In type IIa and IIb subjects the respective changes in median levels were: total cholesterol, -7.5 and -8.5%; trig lycerides, -35.6 and -54.4%; HDL-cholesterol, +9.0 and +11.0%; and Lp[ a], -17.2 and +6.1%. Before and after gemfibrozil treatment, 7 type II a and 10 type IIb subjects were given a 100 g/2 m(2) oral-fat load; tr iglycerides and Lp[a] were measured post-prandially at 0, 2, 4, 6, 8, and 10 h. The differences between before- and after-gemfibrozil post-p randial curve integrated areas (PPCIA) were compared for triglycerides and Lp[a]. The changes in median PPCIA for triglycerides in types IIa and IIb were -54% and -53%, and for Lp[a] were -8% and +8%, respectiv ely. These results indicate i) that the levels of Lp[a] are about 2 ti mes higher in type IIa than IIb subjects, and ii) that although gemfib rozil elicits a rather uniform decrease in fasting and post-prandial t riglyceride levels in type IIa and IIb patients, the drug causes heter ogeneous changes in Lp[a], suggesting that different metabolic mechani sms may be dominant in subjects showing opposing effects.