INTERACTIONS OF PLATELETS, MACROPHAGES, AND LIPOPROTEINS IN HYPERCHOLESTEROLEMIA - ANTIATHEROGENIC EFFECTS OF HMG-COA REDUCTASE INHIBITOR THERAPY

To assess the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA ) reductase inhibitors on plasma cholesterol concentrations and on pla telet aggregation, lovastatin or fluvastatin, 40 mg daily, was given t o hypercholesterolemic patients. After 24 weeks, plasma low-density li poprotein (LDL) cholesterol concentrations were reduced by 37% after l ovastatin therapy and 29% after fluvastatin therapy. The platelet chol esterol/phospholipid ratio was reduced by 33% and 26%, respectively. P latelet aggregation was significantly reduced by 12-15% (p < 0.01) aft er 4 weeks of therapy with either agent. Lovastatin or fluvastatin the rapy reduced platelet aggregation through an in vivo hypocholesterolem ic action on the platelet cholesterol content and also through a direc t effect on platelet function, as a result of drug binding to the plat elets. We also studied the effect of these HMG-CoA reductase inhibitor s on LDL susceptibility to oxidation. LDL oxidation (induced by copper ions) was reduced by 31% after lovastatin therapy and by 37% after fl uvastatin therapy. The inhibitory effect of HMG-CoA reductase inhibito rs on LDL oxidation involved their stimulatory effect on the removal o f LDL from the circulation and a direct binding effect of the drugs to the lipoprotein. Because HMG-CoA reductase inhibitors can inhibit pla telet aggregation, macrophage foam cell formation, and LDL oxidation, major contributors to atherogenesis, the use of these drugs can signif icantly attenuate the atherosclerotic process.