Plasma high density lipoprotein particle size alteration by simvastatin treatment in patients with hypercholesterolaemia.

Twenty-two patients with pronounced hypercholesterolaemia were treated with simvastatin in increasing doses, i.e. 10, 20 and 40 mg O.D. Each treatment regimen had a duration of 6 weeks. In addition to the expected low density lipoprotein (LDL)-lowering effect, simvastatin altered the plasma HDL particle size spectrum by selective elevation of the plasma HDL2b and HDL3a levels, as defined by polyacrylamide gradient gel electrophoresis (gge). While the reduction in LDL cholesterol by simvastatin was dose dependent, the effect on HDL was maximal already at 10 mg daily. On treatment with simvastatin 10 mg O.D., the plasma HDL2b and HDL3a concentrations increased by 30% (P less than 0.001) and 12% (P less than 0.01) respectively. On the corresponding treatment with simvastatin LDL cholesterol decreased by 31% (P less than 0.001). The very low density lipoprotein (VLDL) cholesterol to triglyceride ratio was significantly lowered by treatment with 10 mg simvastatin O.D. suggesting a compositional change in VLDL. Positive univariate correlations between treatment-induced decreases in plasma HDL3b/3c levels and VLDL triglyceride concentration were seen. It is suggested that inhibition of cholesterol synthesis in hypercholesterolaemic subjects by simvastatin treatment alters the composition of VLDL, which may affect the close relation between HDL and VLDL, in turn producing selective elevations of the plasma HDL2b and HDL3a levels.