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

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<0.01). Compared with pretreatment values, simvastatin significantly lowered plasma levels of MMP-9, TF, and PAI-1 (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<0.001; r=−0.482, P=0.005 and r=−0.590, P<0.001, respectively). Of interest, there were significant correlation between pretreatment or percent changes in MMP-9 levels and pretreatment or percent changes in PAI-1 antigen (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.