Association of MMPs and TIMPs With the Occurrence of Atrial Fibrillation: A Systematic Review and Meta-analysis

Background: The roles of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the occurrence of atrial fibrillation (AF) remain inconclusive. Methods: We conducted a systematic review and meta-analysis of observational studies to evaluate the associations of MMPs and TIMPs in blood and atrial tissues with AF risk. A subgroup analysis was performed to explore the potential sources of heterogeneity. Results: A total of 33 studies met our inclusion criteria. Patients with AF had significantly higher messenger RNA (mRNA) levels of MMP-1 in atrial tissue than did the controls, with a pooled standardized mean difference (SMD) of 0.54 (95% confidence interval [CI], 0.30-0.78; P < 0.001). The positive pooled estimates of studies of MMP-2 and MMP-9 in circulating proteins and atrial tissue mRNA and proteins were likely to be susceptible to the effects of significant publication bias. Decreased circulating TIMP-2 levels were significantly associated with increased risk of AF, with a pooled SMD of -.49 (95% CI, -.97 to -0.01; P = 0.04). Conclusions: Increased MMP-1 in tissue mRNA and decreased circulating TIMP-2 levels are significantly associated with increased AF risk. The positive associations of MMP-2 and MMP-9 in blood and atrial tissue with AF risk have significant publication bias. Prospective registries of biomarker research and strict confirmation to reporting guidelines are needed in this field.