Sex Differences in the Burden of Atrial Fibrillation/Flutter and Associated Heart Failure Stratified by Age at Onset

BACKGROUND: Early-onset atrial fibrillation/flutter (AF/AFL), defined as AF/AFL onset before age 45 years, can lead to adverse outcomes including heart failure (HF). The sex-specific patterns of early-onset AF/AFL and associated HF remain poorly understood, particularly in comparison with late-onset AF/AFL. METHODS: Using data from Global Burden of Disease (GBD) 2021, we report the age-standardized rates (ASRs) per 100,000 population and changes from 1990 to 2021 based on sexes, regions and 204 countries. The contributions of risk factors, decomposition methodology, slope index of inequality and Bayesian age-period-cohort models were utilized to assess epidemiological trends, sex disparities, and projected burdens to 2050. All the analyses were performed in both early-onset and late-onset AF/AFL. RESULTS: Globally, the total number of early-onset AF/AFL incident cases was 204 thousand in 2021, accounting for 4.5% of all cases. The male-to-female ratio in global prevalence ASR was 1.62, which suggested greater sex disparities than late-onset AF/AFL. Sex-specific risk factors included smoking and high alcohol use in males and high BMI in females. The global prevalence ASR of associated HF showed a sustained increase through 2050, with a female predominance. CONCLUSION: The epidemiological patterns in early-onset AF/AFL exhibited significant sex-specific variations and differed from those observed in late-onset AF/AFL. Future efforts should prioritize early detection, risk stratification, and tailored interventions to curb complications, particularly HF progression.