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Association of hemostatic markers with atrial fibrillation: a meta-analysis and meta-regression.

Wu N, Tong S, Xiang Y, Wu L, Xu B, Zhang Y, Ma X, Li Y, Song Z, Zhong L - PLoS ONE (2015)

Bottom Line: 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).Increased circulating hemostatic factors (PF-4, BTG, P-selectin, D-dimer, fibrinogen, TAT, F1+2, AT- III, and vWf) are significantly associated with AF.

View Article: PubMed Central - PubMed

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.

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.

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Flow diagram of the literature search and study selection.
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pone.0124716.g001: Flow diagram of the literature search and study selection.

Mentions: A total of 661 records were retrieved after the primary literature search. After screening the titles and abstracts, 531 studies were excluded; 106 potentially relevant full-text articles were reviewed, and 59 studies were included in the meta-analysis (Fig 1). Of the 59 included studies, 35 studies investigated the association between platelet activation markers and AF, with a total of 2730 cases and 2371 controls [5–9, 13, 23, 24, 26–52]. There were 48 studies examining the association between coagulation activation markers and AF, including 5412 AF cases and 29292 controls [5, 7, 8, 11–14, 24, 25, 27, 29, 31, 33, 34, 36–39, 41–43, 45–48, 50–72]. A total of 11 studies investigated the association between fibrinolytic function markers and AF, with 631 patients and 6558 controls [11–13, 31, 45, 50, 59, 61, 63, 67, 72]. Finally, 19 studies examined the association between endothelial function markers and AF, with 2502 cases and 15289 controls [7, 13, 14, 24, 27, 31, 34, 37, 41–43, 46, 50–52, 57, 59, 64, 71]. The mean age of AF patients ranged from 37.0 to 81.5. All case-control and cohort studies had a quality score of at least 6 (S2 Table).


Association of hemostatic markers with atrial fibrillation: a meta-analysis and meta-regression.

Wu N, Tong S, Xiang Y, Wu L, Xu B, Zhang Y, Ma X, Li Y, Song Z, Zhong L - PLoS ONE (2015)

Flow diagram of the literature search and study selection.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401562&req=5

pone.0124716.g001: Flow diagram of the literature search and study selection.
Mentions: A total of 661 records were retrieved after the primary literature search. After screening the titles and abstracts, 531 studies were excluded; 106 potentially relevant full-text articles were reviewed, and 59 studies were included in the meta-analysis (Fig 1). Of the 59 included studies, 35 studies investigated the association between platelet activation markers and AF, with a total of 2730 cases and 2371 controls [5–9, 13, 23, 24, 26–52]. There were 48 studies examining the association between coagulation activation markers and AF, including 5412 AF cases and 29292 controls [5, 7, 8, 11–14, 24, 25, 27, 29, 31, 33, 34, 36–39, 41–43, 45–48, 50–72]. A total of 11 studies investigated the association between fibrinolytic function markers and AF, with 631 patients and 6558 controls [11–13, 31, 45, 50, 59, 61, 63, 67, 72]. Finally, 19 studies examined the association between endothelial function markers and AF, with 2502 cases and 15289 controls [7, 13, 14, 24, 27, 31, 34, 37, 41–43, 46, 50–52, 57, 59, 64, 71]. The mean age of AF patients ranged from 37.0 to 81.5. All case-control and cohort studies had a quality score of at least 6 (S2 Table).

Bottom Line: 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).Increased circulating hemostatic factors (PF-4, BTG, P-selectin, D-dimer, fibrinogen, TAT, F1+2, AT- III, and vWf) are significantly associated with AF.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus