Effect of gemfibrozil on levels of lipoprotein[a] in type II hyperlipoproteinemic subjects.

Plasma lipoprotein[a] (Lp[a]) levels are highly correlated with angiographically 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 related, 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 efficacy of the drug in altering lipid and lipoprotein levels was different 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% triglycerides, -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 IIa and 10 type IIB subjects were given a 100 g/2 m2 oral-fat load; triglycerides and Lp[a] were measured post-prandially at 0, 2, 4, 6, 8, and 10 h. The differences between before- and after-gemfibrozil post-prandial 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%, respectively. These results indicate i) that the levels of Lp[a] are about 2 times higher in type IIa than IIb subjects, and ii) that although gemfibrozil elicits a rather uniform decrease in fasting and post-prandial triglyceride levels in type IIa and IIb patients, the drug causes heterogeneous changes in Lp[a], suggesting that different metabolic mechanisms may be dominant in subjects showing opposing effects.