EFFECTS OF PRAVASTATIN ON APOLIPOPROTEIN-SPECIFIC HIGH-DENSITY-LIPOPROTEIN SUBPOPULATIONS AND LOW-DENSITY-LIPOPROTEIN SUBCLASS PHENOTYPES IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA

The HMG-CoA reductase inhibitor class of cholesterol-lowering agents r educes very low density lipoproteins (VLDL) and low density lipoprotei ns (LDL) and slightly increases high density lipoproteins (HDL). Howev er, the effects of these agents on subclasses within the LDL and HDL f ractions are not well understood. We have employed an HMG-CoA reductas e inhibitor, pravastatin, to determine if LDL subclass phenotypes, as determined by gradient gel electrophoresis, and HDL particles containi ng both apolipoprotein (apo) A-I and A-II, Lp(AI w AII), and those con taining apo A-I but not A-II, Lp(AI w/o AII) are affected by pravastat in (10 mg daily). Twenty-four subjects with LDL-cholesterol (LDL-C) > 160 mg/dl, triglyceride (TG) < 350 mg/dl and no recent myocardial infa rction or secondary causes of hypercholesterolemia were enrolled. Comp ared with an age- and sex-matched normolipidemic reference group (cont rols), the hypercholesterolemic subjects had reduced levels of Lp(Al w /o AII) and increased levels of Lp(AI w All) at baseline. In addition, both of their HDL subpopulations had significantly more small (7.0-8. 2 nm) particles (P < 0.02 and 0.0001) but significantly fewer large (9 .2-11.2 nm) particles (P < 0.002 and 0.0001). Pravastatin induced stat istically significant (P < 0.001) reductions in plasma total C (15%), LDL-C (18%), and apo B (16%). While apo A-I and A-II levels increased 5% (P < 0.001) and 6% (P < 0.05), respectively, concentration, composi tion, and size abnormalities in Lp(AI w AII) and Lp(AI w/o AII) persis ted. Lp(a), apo E and cholesteryl ester transfer protein (CETP) levels also did not change. Although changes in LDL subclass phenotypes were observed, all changes involved the intermediate phenotype, and no sig nificant changes in LDL peak particle diameter were seen in either gro up. Interrelationships between CETP, LDL subclass phenotypes and HDL s ubpopulations were also seen. Conclusions: Although pravastatin decrea sed plasma apo B and LDL lipid concentrations, no major changes were s een in LDL subclass phenotypes or HDL subpopulations even in the prese nce of abnormalities associated with arteriosclerosis. Similarly, CETP , which is believed to play a role in HDL and LDL particle size distri bution, did not change with pravastatin treatment. Further research is needed to determine the pathophysiological basis of abnormal HDL and LDL subclasses in hypercholesterolemia and explore methods of rectifyi ng the abnormalities.