title: Association of hemostatic markers with atrial fibrillation: a meta-analysis and meta-regression.
abstract: BACKGROUND
  There is growing evidence that indicates the presence of a prothrombotic state in atrial fibrillation (AF). However, the role of hemostatic markers in AF remains inconclusive.
  
  
  METHODS
  We conducted a meta-analysis of observational studies to evaluate the association between hemostatic markers and AF. A meta-regression was performed to explore potential sources of heterogeneity.
  
  
  RESULTS
  A total of 59 studies met our inclusion criteria for the meta-analysis. For platelet activation, increased circulating platelet factor-4, β-thromboglobulin (BTG) and P-selectin were significantly higher in AF cases compared with controls (standardized mean difference [SMD][95% confidence interval (CI)]: 1.72[0.96-2.49], 1.61[1.03-2.19] and 0.50[0.23-0.77], respectively). For coagulation activation, increased levels of plasma D-dimer, fibrinogen, thrombin-antithrombin, prothrombin fragment 1+2, and antithrombin-III were significantly associated with AF (SMD[95% CI]: 1.82[1.38-2.26], 0.72[0.55-0.89], 0.42[0.13-0.72], 1.00 [0.00-1.99] and 1.38[0.16-2.60], respectively). For fibrinolytic function, tissue-type plasminogen activator and plasminogen activator inhibitor-1 were significantly increased in AF cases compared with controls (SMD[95% CI]: 0.86[0.04-1.67] and 0.87[0.28-1.47], respectively) but the associations became nonsignificant after performing subgroup analysis by anticoagulants treatment status. For endothelial function, increased von Willebrand factor was significantly associated with AF (SMD, 0.79; 95% CI, 0.60-0.99); however, no association was observed for soluble thrombomodulin (SMD, 0.60; 95% CI, -0.13-1.33).
  
  
  CONCLUSIONS
  Increased circulating hemostatic factors (PF-4, BTG, P-selectin, D-dimer, fibrinogen, TAT, F1+2, AT- III, and vWf) are significantly associated with AF. Future research is necessary to elucidate the precise mechanism of the prothrombotic state and how hemostatic markers promote thromboembolism in AF.
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 Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Shifei
authors.initials: S
authors.lastname: Tong
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: 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: Yao
authors.initials: Y
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: Xiangyu
authors.initials: X
authors.lastname: Ma
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.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
mesh_terms: D001281:Atrial Fibrillation / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000502:physiology*; D010978:Platelet Factor 4 / Q000097:blood; D001620:beta-Thromboglobulin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D019007:P-Selectin; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4