Effects of lovastatin and gemfibrozil on high-density lipoprotein subfraction density and composition in patients with familial hypercholesterolemia.

The effects of gemfibrozil and lovastatin treatment on composition and hydrated density distribution of high-density lipoprotein (HDL) were studied in 21 patients with heterozygous familial hypercholesterolemia with the use of HDL density gradient ultracentrifugation. At baseline the patients with familial hypercholesterolemia had a markedly reduced or missing HDL2 subfraction and their HDL3 was more dense with reduced content of cholesteryl ester and increased content of triglyceride compared with HDL of control subjects with normal lipid values. Gemfibrozil and lovastatin caused primarily similar alterations in HDL components in HDL2 and HDL3 subfractions. Both agents increased apolipoprotein AI and apolipoprotein AII concentrations significantly in HDL2, whereas the apolipoprotein changes in HDL3 were relatively smaller. The difference between the effects of these two agents was related to the HDL lipid composition. Gemfibrozil increased the cholesterol concentrations of HDL2 and HDL3 (p less than 0.05 for both), and lovastatin caused significant increases in HDL2 (p less than 0.05) and HDL3 phospholipids (p less than 0.01). The observed similarity of qualitative alterations in HDL subfractions produced by these two agents in patients with familial hypercholesterolemia differs from those reported in other types of hyperlipidemia and is probably a consequence of the basic abnormalities in HDL that are characteristic of familial hypercholesterolemia.