Stroke risk in women with atrial fibrillation

Abstract

Background and aims: Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF.

Methods: Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care.

Results: The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years.

Conclusion: Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.

Keywords: Atrial Fibrillation; Female sex; Stroke.

Structured Graphical Abstract

Higher stroke risk among women with atrial fibrillation (AF) may be related to inequities in cardiovascular care, suggesting that reducing sex differences in cardiovascular care may attenuate the excess stroke risk in females with AF. BP, blood pressure; CHA2DS2-VASc, congestive heart failure, hypertension, age ≥75 years (doubled), diabetes, stroke (doubled), vascular disease, age 66 to 74 years, and sex category (female); F, female; LDL-C, low density lipoprotein cholesterol; M, male.

Figure 1

Cohort flow diagram. The number of people with documented atrial fibrillation diagnoses, the exclusion criteria, and the number of people excluded for each criterion are presented for males and females.

Figure 2

Age distribution among males and females with newly diagnosed atrial fibrillation. This histogram presents the proportion of males and females at each age within the cohort of people aged ≥66 years with newly diagnosed atrial fibrillation. F, female; M, male.

Figure 3

Adjusted hazard ratios for stroke associated with female sex. Model 1 includes the variables in the conventional CHA₂DS₂-VASc model: congestive heart failure, hypertension, age ≥75 years (doubled), diabetes, stroke (doubled), vascular disease, age 66 to 74 years, and sex category (female). Models 2 and 3 incorporated an interaction term between age and sex, with age handled as a continuous variable using restricted cubic splines utilizing five knots placed at the following percentiles: 5%, 27.5%, 50%, 72.5%, and 95%. Model 3 further accounted for baseline multimorbidity, markers of cardiovascular care as well as anticoagulation as a time-varying covariate.