Atrial fibrillation in women versus men: etiology, pathophysiology, treatment, and prognosis
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Atrial fibrillation (AF) is the most common arrhythmia, and it predominantly occurs older individuals. Its prevalence is expected to rise as the general population ages. Men have a higher incidence of the disease, but since women have longer lifespans, the absolute numbers of patients with AF are similar across genders. There have been observed differences in the manifestation and outcomes of AF between men and women. Atrial fibrillation has been shown to be partially heritable and might be inherited differently by males and females. The distribution of risk factors has been shown to vary by sex: women tend to present at an older age with comorbid diabetes mellitus, hypertension, and valvular heart disease, while men tend to present with comorbid coronary heart disease. Women with atrial fibrillation have reported worse quality of life, longer duration of symptoms, and atypical symptoms not reported by men. The variations in clinical presentation may be explained by baseline cardiac structural and electrical differences. Men tend to have larger heart sizes, including left atria size and left ventricular wall thickness, which increases the risk of AF. Women tend to have more severe atrial fibrosis, which also increases the risk of AF. Cardiac electrophysiological differences may be impacted by sex hormones. Estrogen and testosterone enact opposite effects on cardiac ion concentrations and action potentials, and thus may affect arrhythmogenesis in men and women. The use of hormone replacement due to menopause has been steadily increasing; atrial fibrillation and hormone replacement overlap in a large number of female patients, but little research has been done into the interaction between the change in hormones and atrial fibrillation. The safety and efficacy of the major treatment options for atrial fibrillation have been compared and studied in men, but women have been underrepresented in these trials. Rhythm and rate control have been shown to yield similar morbidity and mortality in men, but rhythm control has led to worse prognosis in women. While rate control overall may be a better strategy for women, different rate control medications have different safety profiles. Digoxin, a rate control drug, increases the risk of breast cancer, but is the treatment most prescribed to women. Women are more likely to be on pharmacotherapy and are less likely to be referred for electrical cardioversion and ablation, even though studies have found that ablation lowers rates of cardiac and all-cause mortality. Women are also less likely than men to be given anticoagulant therapy to mitigate the risk of stroke, despite female sex being an independent risk factor for AF-associated stroke. The differences in treatment likely explain the observed differences in clinical outcomes between the sexes. Atrial fibrillation in women is associated with higher risks of stroke, cardiac events, cardiovascular mortality, and all-cause mortality. Furthering our understanding of atrial fibrillation is vital for improving outcomes in female patients.