The effect of simvastatin treatment on the low-density lipoprotein subfraction profile and composition in familial hypercholesterolaemia.

The effect of simvastatin treatment on the low-density lipoprotein (LDL) subfraction profile was studied in 26 patients with familial hypercholesterolaemia. Before treatment LDL consisted of three LDL subfractions, using density-gradient ultracentrifugation (LDL1, LDL2 and LDL3) present in a relatively narrow density range (d = 1.030-1.045 g/ml). Simvastatin did not influence this profile with respect to the number and density range of the LDL subfractions. However, the composition of the isolated LDL subfractions changed after treatment, as evidenced by the reversal towards normal of the increased cholesterol/protein ratio (mean 1.51 before vs. 1.38 after therapy, p < 0.01; mean 1.36 in normolipidaemic subjects). When the subjects were stratified by their plasma triglyceride levels or the change in plasma triglycerides during simvastatin therapy, a strong dependence of the LDL subfraction profile and its composition on plasma triglyceride levels was observed; increasing plasma triglyceride levels were associated with a more dense LDL subfraction profile, characterized by a high relative contribution of dense LDL3 to total LDL and changes in LDL composition, reflected by a relatively low cholesterol/protein ratio. Our results indicate that in patients with familial hypercholesterolaemia: (1) plasma triglyceride levels have an important role in determining the properties of LDL and (2) simvastatin treatment results in changes in composition of LDL, which may affect the intrinsic metabolic characteristics and thus the atherogenic potential of LDL.