Effects of statin on plaque stability and thrombogenicity in hypercholesterolemic patients with coronary artery disease

Abstract Objective: Plaque stability and thrombogenicity contribute to development and clinical expression of atherosclerosis. Experimental studies have shown that lipoproteins or mevalonate regulate matrix metalloproteinase (MMP)-9, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1) expression, providing nonlipid mechanism. Methods: We administered simvastatin 20 mg daily during 14 weeks to 32 hypercholesterolemic patients with coronary artery disease. Results: Compared with pretreatment values, simvastatin significantly lowered lipoprotein levels (all P P =0.009, P =0.032, and P =0.007, respectively). There were significant inverse correlations between pretreatment MMP-9, TF activity or PAI-1 antigen and the degree of change in those levels after simvastatin ( r =−0.793, P r =−0.482, P =0.005 and r =−0.590, P r =0.293, P =0.019 and r =0.375, P =0.034, respectively). However, no significant correlations between lipoprotein levels and levels of plaque stability or thrombogenicity markers were determined. Conclusions: Reduction of plaque stability and thrombogenicity markers with statin may contribute to the cardiovascular event reduction and explain the early clinical benefit in clinical trials, independent of lipoprotein changes.