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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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Association between fibrinolytic function makers and AF.A. Tissue-type plasminogen activator and AF; B. Plasminogen activator inhibitor-1 and AF. Forest plots of SMD and overall SMD with 95% CI between AF cases and controls. Black diamonds indicate the SMD, with the size of the square inversely proportional to its variance, and horizontal lines represent the 95% CI. The pooled results are indicated by the black hollow diamond. AF, atrial fibrillation; tPA, tissue-type plasminogen activator; PAI-1, plasminogen activator inhibitor-1; SMD, standardized mean difference.
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pone.0124716.g004: Association between fibrinolytic function makers and AF.A. Tissue-type plasminogen activator and AF; B. Plasminogen activator inhibitor-1 and AF. Forest plots of SMD and overall SMD with 95% CI between AF cases and controls. Black diamonds indicate the SMD, with the size of the square inversely proportional to its variance, and horizontal lines represent the 95% CI. The pooled results are indicated by the black hollow diamond. AF, atrial fibrillation; tPA, tissue-type plasminogen activator; PAI-1, plasminogen activator inhibitor-1; SMD, standardized mean difference.

Mentions: The indicators of fibrinolytic function included in this meta-analysis were tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). A meta-analysis of 9 studies for tPA and 11 studies for PAI-1 determined that both markers were significantly increased in AF cases compared with controls, with a pooled SMD of 0.86 (95% CI, 0.04–1.67; P = 0.041) and 0.87 (95% CI, 0.28–1.47; P = 0.004), respectively (Fig 4A and 4B). A subgroup analysis stratified by anticoagulants treatment status was performed. For both tPA and PAI-1, the associations became nonsignificant for all subgroups (S5 Fig, S6 Fig). There was significant heterogeneity among the studies investigating tPA and PAI-1, with an I2 of approximately 96% (Table 1). However, univariate meta-regression analyses did not identify any potential sources of heterogeneity for tPA and PAI-1(S3 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)

Association between fibrinolytic function makers and AF.A. Tissue-type plasminogen activator and AF; B. Plasminogen activator inhibitor-1 and AF. Forest plots of SMD and overall SMD with 95% CI between AF cases and controls. Black diamonds indicate the SMD, with the size of the square inversely proportional to its variance, and horizontal lines represent the 95% CI. The pooled results are indicated by the black hollow diamond. AF, atrial fibrillation; tPA, tissue-type plasminogen activator; PAI-1, plasminogen activator inhibitor-1; SMD, standardized mean difference.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124716.g004: Association between fibrinolytic function makers and AF.A. Tissue-type plasminogen activator and AF; B. Plasminogen activator inhibitor-1 and AF. Forest plots of SMD and overall SMD with 95% CI between AF cases and controls. Black diamonds indicate the SMD, with the size of the square inversely proportional to its variance, and horizontal lines represent the 95% CI. The pooled results are indicated by the black hollow diamond. AF, atrial fibrillation; tPA, tissue-type plasminogen activator; PAI-1, plasminogen activator inhibitor-1; SMD, standardized mean difference.
Mentions: The indicators of fibrinolytic function included in this meta-analysis were tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). A meta-analysis of 9 studies for tPA and 11 studies for PAI-1 determined that both markers were significantly increased in AF cases compared with controls, with a pooled SMD of 0.86 (95% CI, 0.04–1.67; P = 0.041) and 0.87 (95% CI, 0.28–1.47; P = 0.004), respectively (Fig 4A and 4B). A subgroup analysis stratified by anticoagulants treatment status was performed. For both tPA and PAI-1, the associations became nonsignificant for all subgroups (S5 Fig, S6 Fig). There was significant heterogeneity among the studies investigating tPA and PAI-1, with an I2 of approximately 96% (Table 1). However, univariate meta-regression analyses did not identify any potential sources of heterogeneity for tPA and PAI-1(S3 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