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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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Related in: MedlinePlus

Association between endothelial function markers and AF.A. Von Willebrand factor and AF; B. Soluble thrombomodulin 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; vWf, von Willebrand factor; sTM, soluble thrombomodulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; aAF, acute AF; SMD, standardized mean difference.
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pone.0124716.g005: Association between endothelial function markers and AF.A. Von Willebrand factor and AF; B. Soluble thrombomodulin 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; vWf, von Willebrand factor; sTM, soluble thrombomodulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; aAF, acute AF; SMD, standardized mean difference.

Mentions: According to a meta-analysis of 19 studies, plasma von Willebrand factor (vWf) was significantly elevated in AF patients compared with controls, with a pooled SMD of 0.79 (95% CI, 0.60–0.99; P<0.001) (Fig 5A). No significant association was observed between soluble thrombomodulin (sTM) and AF (pooled SMD 0.60; 95% CI, -0.13–1.33; P = 0.107) (Fig 5B). A univariate meta-regression analysis indicated that study design and gender had a significant effect on the level of vWf (S3 Table). However, the test for multivariate model was borderline significant (P = 0.0505) (S4 Table). A subgroup analysis determined that the associations between vWf and AF were significant for both case-control and cohort studies (S7 Fig). The results of subgroup analyses after grouping by anticoagulants treatment status were materially consistent with overall effects (S8 Fig).


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 endothelial function markers and AF.A. Von Willebrand factor and AF; B. Soluble thrombomodulin 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; vWf, von Willebrand factor; sTM, soluble thrombomodulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; aAF, acute AF; SMD, standardized mean difference.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124716.g005: Association between endothelial function markers and AF.A. Von Willebrand factor and AF; B. Soluble thrombomodulin 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; vWf, von Willebrand factor; sTM, soluble thrombomodulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; aAF, acute AF; SMD, standardized mean difference.
Mentions: According to a meta-analysis of 19 studies, plasma von Willebrand factor (vWf) was significantly elevated in AF patients compared with controls, with a pooled SMD of 0.79 (95% CI, 0.60–0.99; P<0.001) (Fig 5A). No significant association was observed between soluble thrombomodulin (sTM) and AF (pooled SMD 0.60; 95% CI, -0.13–1.33; P = 0.107) (Fig 5B). A univariate meta-regression analysis indicated that study design and gender had a significant effect on the level of vWf (S3 Table). However, the test for multivariate model was borderline significant (P = 0.0505) (S4 Table). A subgroup analysis determined that the associations between vWf and AF were significant for both case-control and cohort studies (S7 Fig). The results of subgroup analyses after grouping by anticoagulants treatment status were materially consistent with overall effects (S8 Fig).

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