Stroke Risk in Women With Atrial Fibrillation
- Female patients with AF are more likely to be diagnosed in the emergency department rather than clinician office, less likely to be assessed by cardiologists in routine CV care before and after AF diagnosis, less likely to receive statins or get LDL-C testing, and more likely to have higher systolic blood pressure and LDL-C levels.
- There is a sex- and age-dependent modification in the hazard ratio for stroke in females such that the female sex is independently associated with higher stroke risk in those aged >80 years, but not in younger people.
- These data highlight the need to reduce sex-based inequities in CV care in older people with AF, as they may underlie the higher stroke risk observed among female patients.
For patients with atrial fibrillation (AF), what are the sex differences in age and cardiovascular (CV) care, and what is their relationship with stroke?
This was a large population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. The key independent measure was female sex. Female sex has been associated with higher rates of stroke in AF after adjustment for other CHA2DS2-VASc factors. Covariates of interest in the current trial included other CHA2DS2-VASc risk factors such as heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack, and vascular disease. The authors also studied several markers of CV care such as neighborhood-level material deprivation is a marker of neighborhood residents’ inability to attain basic material needs, location of first AF diagnosis, receipt of echocardiography, anticoagulation use, and adjunct therapy such as antihypertensive and statin therapy in eligible patients.
The primary outcome was hospitalization with a diagnosis of ischemic stroke. Follow-up was limited to 2 years after AF diagnosis, since people with AF frequently acquire additional stroke risk factors over time. 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 modeled 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 CV care.
Of 354,254 individuals with AF (median age 78 years), about 49% were female. Females were more likely to be diagnosed in emergency departments (30% vs. 28%) and less likely to receive cardiologist assessments before (11% vs. 17%) and after AF diagnosis (31% vs. 37%), statins (54% vs. 65%), or low-density lipoprotein cholesterol (LDL-C) testing (49% vs. 55%), 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 CV care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years.
This population-based study examined sex differences in age and CV care to determine their relationship to the higher stroke risk in females with AF. Despite having higher stroke incidence, females with AF were less likely to be assessed by cardiologists, get LDL-C testing, or receive statins. Females with AF also had higher LDL-C levels and higher blood pressure than their male counterparts indicating less optimal control of CV risk factors associated with AF. Additionally, the HR for stroke associated with female sex was age-dependent, such that it was only associated with increased stroke hazard at older ages (>80 years).
Female sex is assigned one point in the CHA2DS2-VASc score, as it is associated with higher stroke risk in AF. Recent studies suggest that female sex is a risk modifier for AF-associated stroke rather than an independent risk factor in all-comers with AF. This study explores the sex- and age-based differences in the hazard for stroke in patients with AF. Older age and inequities in CV care explain the sex differences in AF management and stroke risk in females. This study highlights that there may be greater sex-based inequities in risk factor control among older patients, so that the magnitude of a risk factor (e.g., blood pressure) may be higher in older females than males. It highlights greater need for risk factor control and CV care of older populations, especially women at risk for stroke.
Keywords: Atrial Fibrillation, Geriatrics, Risk Factors, Sex Characteristics, Stroke
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