Are women at lower risk for atrial fibrillation (AF) after accounting for other AF risk factors and do risk factors for AF differ for men vs women?
In this cohort study of 25 119 participants within the Vitamin D and Omega-3 Trial (VITAL) Rhythm Study, women were at greater risk for developing AF than men when height and weight, rather than body mass index, were controlled for in multivariable models. AF risk factors were similar for women vs men.
Results suggest that for a given height and weight, women are at higher risk for incident AF than men, and primary prevention with risk factor modification should be equally effective; these findings emphasize the need for AF prevention in women.
Women have a lower incidence of atrial fibrillation (AF) compared with men in several studies, but it is unclear whether this sex difference is independent of sex differences in prevalent cardiovascular disease (CVD), body size, and other risk factors.
To examine sex differences in AF incidence and whether AF risk factors differ by sex in a contemporary cohort of men and women without prevalent CVD.
Design, Setting, and Participants
This was a prospective cohort analysis within the Vitamin D and Omega-3 Trial (VITAL) Rhythm Study, a randomized trial that examined the effect of vitamin D and ω-3 fatty acid supplementation on incident AF among men 50 years or older and women 55 years or older without a prior history of prevalent AF, CVD, or cancer at baseline. Data were analyzed from September 29, 2020, to June 29, 2021.
Sex, height, weight, body mass index (BMI), body surface area (BSA), and other AF risk factors at study enrollment.
Main Outcomes and Measures
Incident AF confirmed by medical record review.
A total of 25 119 individuals (mean [SD] age, 67.0 [7.1] years; 12 757 women [51%]) were included in this study. Over a median (IQR) follow-up of 5.3 (5.1-5.7) years, 900 confirmed incident AF events occurred among 12 362 men (495 events, 4.0%) and 12 757 women (405 events, 3.2%). After adjustment for age and treatment assignment, women were at lower risk for incident AF than men (hazard ratio [HR], 0.68; 95% CI, 0.59-0.77; P < .001). The inverse association between female sex and AF persisted after adjustment for race and ethnicity, smoking, alcohol intake, hypertension, diabetes (type 1, type 2, gestational), thyroid disease, exercise, and BMI (HR, 0.73; 95% CI, 0.63-0.85; P <.001). However, female sex was positively associated with AF when height (HR, 1.39; 95% CI, 1.14-1.72; P = .001), height and weight (HR 1.49, 95% CI, 1.21-1.82; P <.001), or BSA (HR, 1.25; 95% CI, 1.06-1.49; P = .009) were substituted for BMI in the multivariate model. In stratified models, risk factor associations with incident AF were similar for women and men.
Conclusions and Relevance
In this cohort study, findings suggest that after controlling for height and/or body size, women without CVD at baseline were at higher risk for AF than men, suggesting that sex differences in body size account for much of the protective association between female sex and AF. These data underscore the importance of AF prevention in women.
Siddiqi HK, Vinayagamoorthy M, Gencer B, et al. Sex Differences in Atrial Fibrillation Risk: The VITAL Rhythm Study. JAMA Cardiol. 2022;7(10):1027–1035. doi:10.1001/jamacardio.2022.2825
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