Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation Among Women

Abstract

Importance: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide, with different epidemiological and pathophysiological processes for women vs men and a poorer prognosis for women. Further investigation of sex-specific risk factors associated with AF development in women is warranted.

Objective: To investigate the linear and potential nonlinear associations between sex-specific risk factors and the risk of new-onset AF in women.

Design, setting, and participants: This population-based cohort study obtained data from the 2006 to 2010 UK Biobank study, a cohort of more than 500 000 participants aged 40 to 69 years. Participants were women without AF and history of hysterectomy and/or bilateral oophorectomy at baseline. Median follow-up period for AF onset was 11.6 years, and follow-up ended on October 3, 2020.

Exposures: Self-reported, sex-specific risk factors, including age at menarche, history of irregular menstrual cycle, menopause status, age at menopause, years after menopause, age at first live birth, years after last birth, history of spontaneous miscarriages, history of stillbirths, number of live births, and total reproductive years.

Main outcomes and measures: The primary outcome was new-onset AF, which was defined by the use of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code I48.

Results: A total of 235 191 women (mean [SD] age, 55.7 [8.1] years) were included in the present study. During follow-up, 4629 (2.0%) women experienced new-onset AF. In multivariable-adjusted models, history of irregular menstrual cycle was associated with higher AF risk (hazard ratio [HR], 1.34; 95% CI, 1.01-1.79). Both early menarche (age 7-11 years; HR, 1.10 [95% CI, 1.00-1.21]) and late menarche (age 13-18 years; HR, 1.08 [95% CI, 1.00-1.17]) were associated with AF incidence. Early menopause (age 35-44 years; HR, 1.24 [95% CI, 1.10-1.39]) and delayed menopause (age ≥60 years; HR, 1.34 [95% CI, 1.10-1.78]) were associated with higher risk of AF. Compared with women with 1 to 2 live births, those with 0 live births (HR, 1.13; 95% CI, 1.04-1.24) or 7 or more live births (HR, 1.67; 95% CI, 1.03-2.70) both had significantly higher AF risk.

Conclusions and relevance: Results of this study suggest that irregular menstrual cycles, nulliparity, and multiparity were associated with higher risk of new-onset AF among women. The results highlight the importance of taking into account the reproductive history of women in devising screening strategies for AF prevention.

Figure 1.. Flowchart of the Study Population

AF indicates atrial fibrillation.

Figure 2.. Nonlinear Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation

Model was adjusted for baseline age, race and ethnicity, educational level, body mass index, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, smoking status, history of diabetes, history of coronary heart disease, history of heart failure, history of stroke, use of blood pressure–lowering medication, and use of cholesterol-lowering medication. Shaded areas indicate 95% CIs. HR indicates hazard ratio.