A Literature Review Investigating the Role of Sex and Gender in Atrial Fibrillation Outcomes

Abstract

Atrial fibrillation (AF), the most common cardiac arrhythmia, presents distinct challenges influenced by sex and gender. To preface, sex refers to biological attributes (chromosomal, hormonal, and physiological), while gender involves a set of sociocultural roles, behaviours, and expectations prescribed to individuals according to their attributed-at-birth sex. While men exhibit higher AF prevalence, women face disproportionately severe outcomes, including increased stroke risk, hospitalizations, and mortality. This review explores the interplay of genetic, hormonal, physiological, and environmental factors driving these disparities. Sex-specific genetic pathways, such as mutations in KCN1 and KCNE5, alongside hormonal influences like estrogen's dual effects on cardioprotection and arrhythmogenesis, contribute to variations in AF risk. Additionally, structural and functional differences in the heart, such as ventricular wall thickness and cardiac output, further differentiate AF presentations between sexes. Environmental and sociocultural factors, including chronic stress and underutilization of anticoagulation therapies, exacerbate gender-based inequities, particularly among women. Recognizing these multifaceted influences is crucial for developing personalized prevention, diagnosis, and management strategies. This literature review advocates for integrating sex and gender considerations into clinical guidelines to improve outcomes for all individuals affected by AF.