Female sex as a risk factor for stroke in atrial fibrillation: a nationwide cohort study

J Thromb Haemost. 2012 Sep;10(9):1745-51. doi: 10.1111/j.1538-7836.2012.04853.x.


Background: Female sex has been suggested as a risk factor for stroke/thromboembolism in patients with non-valvular atrial fibrillation (AF) and has therefore been included within risk scores, e.g., the CHA2 DS2 -VASc score, and guidelines.

Objectives: To investigate the risk of stroke/thromboembolism associated with female sex in non-valvular AF patients.

Patients/methods: Using the national Danish registers, we identified non-anticoagulated patients discharged with non-valvular AF (1997-2008), and subdivided the population into three age intervals: < 65, 65-74 and ≥ 75 years. We calculated stroke rates according to sex, and assessed the stroke risk associated with female sex by using Cox regression analysis.

Results: We included 87,202 AF patients, and 44,744 (51.3%) were female. The rate of stroke/thromboembolism for females aged < 65 and 65-74 years was not increased as compared with men, whereas the rate for females aged ≥ 75 years was increased. At both 1-year and 12-year follow-up, female sex did not increase the risk of stroke for patients aged < 75 years. At 1-year follow-up, the hazard ratios associated with female sex were 0.89 (95% confidence interval [CI] 0.70-1.13) and 0.91 (95 CI 0.79-1.05) for patients aged < 65 and 65-74 years, respectively, and being female and aged ≥ 75 years was associated with an increased risk of stroke of 1.20 (95 CI 1.12-1.28).

Conclusion: Female sex was only associated with an increased risk of stroke for AF patients aged ≥ 75 years. Our study suggests that female sex should not be automatically included as an independent stroke/thromboembolic risk factor in guidelines or in the CHA2 DS2 -VASc score, without careful prior consideration of the 'age < 65 and lone AF' criterion.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / complications*
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Humans
  • Regression Analysis
  • Risk Factors
  • Stroke / epidemiology*
  • Stroke / etiology