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.
Son
Ji Won
JW
Cardiology, Gachon Medical School, Inchon, South Korea.
Koh
Kwang Kon
KK
Ahn
Jeong Yeal
JY
Jin
Dong Kyu
DK
Park
Gi Soo
GS
Kim
Dae Sung
DS
Shin
Eak Kyun
EK
D001053:Apolipoproteins / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D014280:Triglycerides; D019821:Simvastatin; D020780:Matrix Metalloproteinase 9