Impact of Statin Therapy on Plasma MMP-3, MMP-9, and TIMP-1 Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

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Abstract

Tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) are associated with the development of atherosclerosis and cardiovascular disease. Statin therapy has been shown to modulate MMPs and TIMP-1 levels, but clinical findings have not been conclusive. This study aimed to systematically review the clinical findings on the impact of statin therapy on plasma MMP-9, MMP-3, and TIMP-1 levels and calculate an effect size for the mentioned effect through a meta-analysis of available data. A total of 10 eligible studies with 11 treatment arms were included in the meta-analysis. Statin therapy had no significant effect on plasma MMP-9 (standardized mean difference [SMD]: −0.23, 95% confidence interval [CI]: −0.69 to 0.24, P = .345) nor MMP-3 concentrations (SMD: −0.004, 95% CI: −0.60 to 0.59, P = .990). However, meta-analysis demonstrated that statin therapy significantly decreases plasma TIMP-1 levels (SMD: −0.30, 95% CI: −0.56 to −0.03, P = .029). Random-effects meta-regression indicated that neither treatment duration nor changes in low-density lipoprotein cholesterol levels are associated with changes in plasma MMP-9 levels following statin therapy. The results of the present meta-analysis suggested a significant reduction in plasma concentrations of TIMP-1, but not MMP-9 and MMP-3, following statin therapy.

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