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Original research
Female sex as a risk factor for ischaemic stroke varies with age in patients with atrial fibrillation
  1. Victor Chien-Chia Wu1,
  2. Michael Wu2,
  3. Victor Aboyans3,
  4. Shang-Hung Chang1,
  5. Shao-Wei Chen4,
  6. Mien-Cheng Chen5,
  7. Chun-Li Wang1,
  8. I-Chang Hsieh1,
  9. Pao-Hsien Chu1,
  10. Yu-Shen Lin6,7
  1. 1 Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
  2. 2 Divison of Cardiovascular Medicine, Arrhythmia Services Section, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA
  3. 3 Department of Cardiology, Dupuytren University Hospital, Limoges, France
  4. 4 Department of Cardiothoracic and Vascular Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
  5. 5 Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
  6. 6 Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
  7. 7 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  1. Correspondence to Dr Yu-Shen Lin, Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 33305, Taiwan; dissertlin{at}


Objectives Female sex is an inconsistent ischaemic stroke risk factor in patients with atrial fibrillation (AF). We hypothesised that the ischaemic stroke risk varies with age among women compared with men.

Methods We retrieved the patients with newly diagnosed AF during 2001–2013 from Taiwan’s National Health Insurance Research Database. Patients with missing information, age <20 years, history of valvular heart disease and surgery, rheumatic heart disease, hyperthyroidism or anticoagulation and/or antiplatelet use were excluded. Propensity score matching (PSM) included patient comorbidities, medications and index date stratified by age and sex groups. Primary outcome was defined as ischaemic stroke at follow-up.

Results After exclusion criteria, 87 369 men and 71 853 women remained for analysis (aged 73.1±14.4 years). After 1:1 PSM, we included 59 583 men (aged 73.5±13.7 years) and 59 583 women (aged 73.4±13.8 years) for analysis. We also stratified patients by age. The ischaemic stroke risk varied with age in women compared with men: lower in the ≤55 years (subdistribution HR (SHR)=0.75, 95% CI 0.62 to 0.90) and 56–65 years (SHR=0.87, 95% CI 0.78 to 0.98) groups, neutral in the 66–75 years group (SHR=1.01, 95% CI 0.94 to 1.08) and adverse in the >75 years group (SHR=1.14, 95% CI 1.09 to 1.19).

Conclusions The female/male ischaemic stroke risk ratio varied with age. Only women aged >75 years had a higher risk, whereas women aged <65 years had a lower risk compared with men. These findings challenge the ‘sex category’ component of the CHA2DS2-VASc score, used to make decision regarding anticoagulation treatment in AF patients.

  • atrial fibrillation
  • female sex
  • anticoagulation
  • ischemic stroke

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  • VC-CW and MW contributed equally.

  • Contributors VCW, MW and YSL contributed to the conception or design of the work and final approval of the version to be published. VCW and YSL contributed to the data collection. VCW, MW, VA, SHC and SWC contributed to the data analysis and interpretation. VCW and MW drafted the article. MCC, CLW, ICH and PHC contributed to the critical revision of the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by Institutional Review Board of Chang Gung Memorial Hospital (IRB No. 201 801 354B0).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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