Female Sex Is Not a Uniform Risk Factor in Atrial Fibrillation

Female sex is a part of the stroke risk stratification in atrial fibrillation (AF), although emerging evidence suggests it may function as a risk modifier rather than an independent risk factor.

This study aimed to determine whether female sex is a risk factor or risk modifier for stroke in patients with AF.

Using TriNetX, nonvalvular AF patients were identified and stratified by sex and age (<65, 65-74, and ≥75 years). Female and male patients were propensity matched for comorbidities and anticoagulation. Analyses were conducted comparing male and female patients with no CHA₂DS₂-VA risk factors beyond age and with one additional CHA₂DS₂-VA risk factor. The risks of stroke and arterial embolism were compared over a 1-year follow-up period.

In patients without additional CHA₂DS₂-VA risk factors or anticoagulation (n = 252,528), female sex was associated with increased stroke risk only among patients aged ≥75 years (HR: 1.244; 95% CI: 1.087-1.423; P = 0.001). Similarly, in patients with one additional CHA₂DS₂-VA risk factor (n = 607,612), stroke risk was increased among female patients ≥75 years (HR: 1.065; 95% CI: 1.014-1.118; P = 0.012).

Female sex acts as a modest risk modifier for thromboembolic stroke. Increased risk is primarily observed in patients with greater comorbidity burden or advanced age (≥75 years).