Effects of bezafibrate on the serum lipoprotein lipid and apolipoprotein composition, lipoprotein triglyceride removal capacity and the fatty acid composition of the plasma lipid esters

Abstract

Bezafibrate has been shown to effectively reduce elevated levels of very low density lipoprotein (VLDL) in hypertriglyceridaemia. It has also been claimed to be particularly effective in increasing high density lipoprotein (HDL) concentrations. In the present study 15 hypertriglyceridaemic patients (9 type IIB, 1 type III and 5 type IV) were investigated before and after 2 months' treatment with bezafibrate (600 mg daily) in an effort to clarify further the effects of the drug on lipoprotein metabolism. The serum triglycerides decreased by 46% ( P < 0.001) corresponding to a significant reduction of both the VLDL (−43%, P < 0.001) and the low density lipoprotein (LDL) (−27%, P < 0.05) triglycerides. The serum cholesterol decreased by 13% ( P < 0.001), mainly due to reduction of the VLDL cholesterol (−51%, P < 0.001). There was no significant reduction of the LDL cholesterol in the whole group (−10%, n.s.). However, if only the patients with hypercholesterolaemia were considered, there was a significant reduction of LDL cholesterol by 19% ( P < 0.01). HDL triglycerides and HDL cholesterol increased by 20% ( P < 0.05) and 22% ( P < 0.001) respectively. While the concentration of apolipoprotein (apo) B decreased by 15% ( P < 0.01) there were significant increases of apo A-I (+14%, P < 0.001) and apo A-II (+30%, P < 0.001) analogous to the increase of HDL lipid concentration. However, the ratio between apo A-I and apo A-II decreased significantly during therapy (−12%, P < 0.001) indicating that the increase of HDL may have preferentially affected the HDL-3 fraction. There were highly significant reductions of both the ratio between LDL and HDL cholesterol (−24%, P < 0.001) and the ratio between apo B and apo A-I (−25%, P < 0.001), changes which should be favourable with regard to atherogenicity. Significant increases of both the plasma post-heparin lipoprotein lipase activity (+20%, P < 0.001) and the fractional removal rate (K 2) at the intravenous fat tolerance test (+30%, P < 0.001) indicate that one of the mechanisms behind the effects of the drug on lipoprotein metabolism may be an increased removal of circulating triglyceride-rich lipoproteins. Bezafibrate treatment caused significant changes in the plasma lipid fatty acid composition, mainly by increasing the mono-unsaturated fatty acids (palmitoleate and oleate) concomitant with a significant decrease in the content of linoleate. Very similar changes have been recorded during clofibrate treatment. The mechanisms behind these changes as well as their significance are at present obscure.