Association of inflammatory and hemostatic markers with stroke and thromboembolic events in atrial fibrillation: a systematic review and meta-analysis

Can J Cardiol. 2015 Mar;31(3):278-86. doi: 10.1016/j.cjca.2014.12.002. Epub 2014 Dec 9.

Abstract

Background: Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes in patients with AF. The prognostic value of inflammatory and hemostatic markers in AF has been widely studied; however, the results of previous studies have been inconclusive.

Methods: We conducted a systematic review and meta-analysis to evaluate the association of inflammatory and hemostatic markers with stroke and thromboembolic events in patients with AF.

Results: A total of 27 studies including 22,176 participants met our inclusion criteria for the systematic review. Our meta-analysis determined that elevated circulating plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin (TAT) were significantly associated with increased risk of stroke in patients with AF (standardized mean difference [SMD], 0.89; 95% confidence interval [CI], 0.20-1.59 and 1.43; 95% CI, 0.40-2.47, respectively). Higher levels of D-dimer were associated with increased subsequent thromboembolic event risk with a pooled hazard ratio of 2.90 (95% CI, 1.22-6.90) for cohort studies and an SMD of 0.93 (95% CI, 0.36-1.50) for case-control studies. There was also very limited evidence indicating that other biomarkers-such as interleukin-6, von Willebrand factor, P-selectin, and mean platelet volume-could predict adverse outcomes in AF.

Conclusions: In conclusion, increased circulating PAI-1 and TAT levels were significantly associated with subsequent stroke in patients with AF, and high levels of D-dimer were associated with thromboembolic events in AF. Further epidemiologic studies are needed to accumulate more evidence on the prognostic role of inflammatory and hemostatic markers in AF.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Anticoagulants / therapeutic use
  • Antifibrinolytic Agents / blood
  • Antithrombin III
  • Atrial Fibrillation / blood*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / diagnosis*
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / mortality
  • Biomarkers / blood
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Humans
  • Interleukin-6 / blood
  • Mean Platelet Volume
  • Peptide Hydrolases / blood*
  • Plasminogen Activator Inhibitor 1 / blood*
  • Predictive Value of Tests
  • Prognosis
  • Selectins / blood
  • Sensitivity and Specificity
  • Serine Proteinase Inhibitors / blood*
  • Stroke / blood*
  • Stroke / etiology
  • Thromboembolism / blood*
  • Thromboembolism / etiology
  • von Willebrand Factor / metabolism

Substances

  • Anticoagulants
  • Antifibrinolytic Agents
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Interleukin-6
  • Plasminogen Activator Inhibitor 1
  • Selectins
  • Serine Proteinase Inhibitors
  • antithrombin III-protease complex
  • fibrin fragment D
  • von Willebrand Factor
  • Antithrombin III
  • Peptide Hydrolases