Abstract 4328: Effect of Statin on Serum Matrix Metalloproteinase Levels as a Sign of Plaque Regression in Patients With Acute Coronary Syndrome: Subanalysis of JAPAN ACS Study
Matrix metalloproteinases (MMP) have been implicated in development of atherosclerosis. MMPs are activated in patients with acute coronary syndrome (ACS). However, little data exists regarding the effect of statin on circulating levels of MMP and the correlation betweenon MMP and plaque volume in patients with ACS. We sought to evaluate the impact of MMP on plaque volume with ACS as post hoc analysis from JAPAN-ACS.
METHODS AND RESULTS: The multicenter JAPAN-ACS trial has revealed that aggressive statin therapy for patients with ACS significantly reduces non-culprit coronary plaque volume evaluated by IVUS. JAPAN-ACS treated 222 coronary disease patients with pitavastatin 4mg/d or atorvastatin 20 mg/d for 10 months. For each patient, MMP-1, 2, 3 and TIMP-1, 2 at baseline and study end was measured. MMP-3 levels were significantly decreased by statin therapy during follow-up period (112.0ng/ml to 81.3ng/ml, p<0.001). There were no significant differences in other markers. Furthermore, MMP-3 reduction was associated with improved hs-CRP during follow-up period. The plaque volume evaluated by volumetric IVUS was reduced by 18%. MMP-3 at the follow-up associated with 10 months plaque volume regression in Q1 as compared to the three higher quartiles (Q2– 4) (−21.3%, −18.4%, −15.7%, −14.5%). MMP-3 reductions were also linearly related to the regression of plaque volume accompanied by statin treatment.
CONCLUSIONS: Decreased MMP-3 by statin is likely to contribute to the vascular protection, which may be mediated through its ability to promote plaque regression. The reduction of these factors by statin administration may provide a new insight into the pleiotropic effects of statins on unstable coronary artery disease.