Women-specific risk factors and risk of incident atrial fibrillation in UK Biobank

Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and carries a large morbidity and mortality risk. Recent evidence suggests differences in epidemiology and pathophysiology of AF between women and men and underscores a poorer prognosis of AF among women. This calls for further investigation regarding the impact of women-specific risk factors on AF development. Purpose To investigate the association between women-specific risk factors and new-onset AF. Methods 235,191 women (mean [standard deviation] age: 55.7 [8.1] years) free of AF and without a history of hysterectomy and/or bilateral oophorectomy from the UK Biobank were included. Various women-specific risk factors were assessed from 2006 to 2010. Follow-up of new-onset AF occurred through October 2020. Cox proportional hazards analyses were performed to investigate prospective associations between each risk factor and incident AF. Additionally, natural splines were used to identify any potential nonlinear associations. Results After a median follow-up of 11.6 (interquartile range: 10.9–12.3) years, 4,629 (2%) women experienced new-onset AF. In fully adjusted models, having experienced irregular menstrual cycle was significantly associated with increased new-onset AF risk [hazard ratio (HR); 95% confidence interval (CI): 1.34; 1.01-1.79]. In addition, nonlinear associations were found between menopausal age, menarcheal age, number of live births, and number of total reproductive years with incident AF. Compared to the reference, early menopause (menopause <45 years of age) or delayed menopause (>60 years) significantly increased risks of incident AF (HR; 95CI: 1.24; 1.10-1.39 and 1.34; 1.01-1.78, respectively). Compared to the reference, both early menarche (menarche ≤11 years) and late menarche (menarche ≥13 years) were associated with AF incidence (HR; 95CI: 1.10; 1.00-1.21 and 1.08; 1.00-1.17, respectively). Compared to women with one or two children, having no children (HR; 95CI: 1.13; 1.04-1.24), or more than six children (HR; 95%CI: 1.67; 1.03-2.70) were associated with higher AF risks. Having reproductive years ≤20 years was significantly associated with incident AF (HR; 95CI: 1.74; 1.07-2.86). Conclusions Having experienced early or delayed menopause, early or late menarche, or irregular menstrual cycles conferred higher risks of incident AF among women in the UK Biobank. Interestingly, both nulliparity and multiparity, compared to having one or two children, were associated with an increased AF risk. Our results highlight the importance of knowledge regarding the reproductive history of women in devising screening strategies for AF prevention.