Key result
Female sex in AF is linked to ~4% lower HF risk after age adjustment.
Why the study?
Females with AF have been reported to have a higher risk of HF than males, but the underlying mechanism and age- and sex-specific risk factors remained unclear.
Does female sex increase the risk of incident heart failure compared to male sex in patients with atrial fibrillation after accounting for age and comorbidities?
Cohort (n=229,878)
Does female sex increase the risk of incident heart failure compared to male sex in patients with atrial fibrillation after accounting for age and comorbidities?
In a large nationwide cohort of patients with incident atrial fibrillation, the higher crude incidence of heart failure in females compared to males is primarily explained by older age, though specific comorbidities like atherosclerosis and anemia confer differential sex-specific risks.
Apparent higher HF risk in females with AF attenuates after age adjustment; observational data leave open residual sex-specific effects.
Background Females with atrial fibrillation (AF) has been reported to have a higher risk of heart failure (HF) than males, although the mechanism remains unclear. Purpose This study aims to explore age- and sex-specific risks for HF in AF patients. Methods Using data from Statistics Netherlands (Centraal Bureau voor de Statistiek, CBS), we included a cohort of incident AF patients without HF from 2015 to 2023. Follow-up started from AF diagnosis until the outcome (incident HF), death or end of follow-up. Incidence rate were calculated and adjusted hazard ratios (aHRs) for HF by age were estimated by Cox regression. Factors associated with HF in AF patients by sex were further examined in an interaction analysis with females without the risk factor serving as refence. Results Among 229,878 included patients (43.9% females, mean age 72.0 ± 12.5 years), 26,730 (11.6%) experienced HF during follow-up (median 2.83 years). Females versus males had a higher incidence rate of HF (3.86, 95%CI 3.79-3.93 versus 3.24, 95%CI 3.19-3.30/100 person-years resp.). Female compared with male sex was associated with a relative risk of HF of 1.18 (95%CI 1.15-1.21), which decreased towards unity after adjusting for age (aHR 0.96, 95%CI 0.94-0.98). Chronic obstructive pulmonary disease, peripheral artery disease, valvular heart disease and chronic kidney disease were consistently associated with incident HF in both sexes (aHRs > 1.5). Among individuals with atherosclerosis, female versus male sex was associated with an increased risk of HF (aHR 1.54, 95%CI 1.46-1.61 versus 1.28, 95%CI 1.23-1.33 resp.). Nevertheless, female versus male sex in anaemia patients was associated with a decreased risk of HF (aHR 1.41, 95%CI 1.34-1.48 versus 1.63 95%CI 1.55-1.71). Conclusion Differences between sexes regarding HF risk were mainly explained by age. However, sex-specific comorbidities were associated with HF. These results support sex- and comorbidity-specific HF risk assessment in AF patients.
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Cheng et al. (2026) conducted a cohort in Incident atrial fibrillation without heart failure (n=229,878). Female sex vs. Male sex was evaluated on Incident heart failure (aHR 0.96, 95% CI 0.94-0.98). Female versus male sex in AF had a higher crude HF risk (RR 1.18; 95% CI 1.15-1.21) that attenuated toward unity after adjusting for age (aHR 0.96; 95% CI 0.94-0.98).
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