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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 platelet activation markers and AF.A. platelet count and AF; B. Mean platelet volume and AF; C. Platelet factor-4 and AF; D. β-thromboglobulin and AF; E. P-selectin 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; MPV, mean platelet volume; PF-4, platelet factor-4; BTG, β-thromboglobulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; SMD, standardized mean difference.
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pone.0124716.g002: Association between platelet activation markers and AF.A. platelet count and AF; B. Mean platelet volume and AF; C. Platelet factor-4 and AF; D. β-thromboglobulin and AF; E. P-selectin 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; MPV, mean platelet volume; PF-4, platelet factor-4; BTG, β-thromboglobulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; SMD, standardized mean difference.

Mentions: The meta-analysis of 14 studies determined that platelet count was not significantly different between AF cases and controls with a pooled SMD -0.29 (95% CI, -0.59–0.02; P = 0.066) (Fig 2A). Mean platelet volume (MPV), circulating levels of platelet factor-4 (PF-4), β-thromboglobulin (BTG) and P-selectin were higher in AF cases than controls, with a pooled SMD of 0.92 (95% CI, 0.12–1.73; P = 0.025), 1.72 (95% CI, 0.96–2.49; P<0.001), 1.61 (95% CI, 1.03–2.19; P<0.001), and 0.50 (95% CI, 0.23–0.77; P<0.001), respectively (Fig 2B–2E).


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 platelet activation markers and AF.A. platelet count and AF; B. Mean platelet volume and AF; C. Platelet factor-4 and AF; D. β-thromboglobulin and AF; E. P-selectin 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; MPV, mean platelet volume; PF-4, platelet factor-4; BTG, β-thromboglobulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; SMD, standardized mean difference.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124716.g002: Association between platelet activation markers and AF.A. platelet count and AF; B. Mean platelet volume and AF; C. Platelet factor-4 and AF; D. β-thromboglobulin and AF; E. P-selectin 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; MPV, mean platelet volume; PF-4, platelet factor-4; BTG, β-thromboglobulin; PAF, paroxysmal AF; PeAF, persistent AF; PtAF, permanent AF; CAF, chronic AF; SMD, standardized mean difference.
Mentions: The meta-analysis of 14 studies determined that platelet count was not significantly different between AF cases and controls with a pooled SMD -0.29 (95% CI, -0.59–0.02; P = 0.066) (Fig 2A). Mean platelet volume (MPV), circulating levels of platelet factor-4 (PF-4), β-thromboglobulin (BTG) and P-selectin were higher in AF cases than controls, with a pooled SMD of 0.92 (95% CI, 0.12–1.73; P = 0.025), 1.72 (95% CI, 0.96–2.49; P<0.001), 1.61 (95% CI, 1.03–2.19; P<0.001), and 0.50 (95% CI, 0.23–0.77; P<0.001), respectively (Fig 2B–2E).

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