TREATMENT OF PRIMARY MIXED HYPERLIPIDEMIA WITH ETOPHYLLINE CLOFIBRATE- EFFECTS ON LIPOPROTEIN-MODIFYING ENZYMES, POSTPRANDIAL LIPOPROTEIN METABOLISM, AND LIPOPROTEIN DISTRIBUTION AND COMPOSITION

In 17 patients with primary mixed hyperlipidemia we studied levels and composition of lipoproteins in fasting plasma,;lipoprotein-modifying enzymes, and postprandial lipoprotein metabolism after an oral fat-tol erance test supplemented with vitamin A before, and 12 weeks after tre atment with etophylline clofibrate. With treatment, fasting plasma cho lesterol, triglycerides, and the levels of very low density lipoprotei ns (VLDL), intermediate density lipoproteins (IDL), and low density li poproteins (LDL) decreased significantly; high density lipoprotein (HD L) cholesterol increased significantly, Treatment caused also an incre ase in the protein content of IDL, a decrease in the triglyceride cont ent of LDL, and an increase in the size of LDL as assessed by gradient gel electrophoresis. Concentrations of triglycerides, chylomicrons, a nd chylomicron remnants after an oral fat load supplemented with vitam in A decreased by 33%, 30%, and 6%, respectively (P < 0.005; P < 0.01; and P < 0.05). The activity of lipoprotein lipase and hepatic lipase in postheparin plasma increased by 51% and 45%, respectively (P < 0.01 ; P < 0.05). We found a decrease in the mass concentration of choleste ryl ester transfer protein (P < 0.05). Stepwise multiple regression an alysis showed that the triglyceride content of LDL is determined prima rily by fasting triglycerides (r = +0.53, P < 0.05; baseline) and chol esteryl ester transfer protein (r = +0.49, P < 0.05; 12 weeks); in con trast, the triglyceride content of HDL, is determined exclusively by a ccumulation of postprandial triglycerides (r = +0.67; P < 0.05; baseli ne) and postprandial chylomicrons (r = +0.87; P < 0.005; 12 weeks). We conclude that hypolipidemic treatment with etophylline clofibrate fav orably affects the cardiovascular risk factor profile in primary mixed hyperlipidemia.