title: Association of MMPs and TIMPs With the Occurrence of Atrial Fibrillation: A Systematic Review and Meta-analysis.
abstract: The roles of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the occurrence of atrial fibrillation (AF) remain inconclusive.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: 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.
authors.forename: Long
authors.initials: L
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Mengxuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China. Electronic address: zhongli28@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
mesh_terms: D001281:Atrial Fibrillation / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D006801:Humans; D020782:Matrix Metalloproteinases / Q000097:blood*; D064887:Observational Studies as Topic; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000097:blood; D012680:Sensitivity and Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases