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

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.