Yuan Liu1, Bin Xu1, Na Wu1, Ying Xiang1, Long Wu1, Mengxuan Zhang1, Jiehua Wang1, Xinghua Chen2, Yafei Li1, Li Zhong3. 1. Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Third Military Medical University, Chongqing, People's Republic of China. 2. Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China. 3. Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China. Electronic address: zhongli28@hotmail.com.
Abstract
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 -0.49 (95% CI, -0.97 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.
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 -0.49 (95% CI, -0.97 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.
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