ImportanceWomen 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresSex, height, weight, body mass index (BMI), body surface area (BSA), and other AF risk factors at study enrollment.Main Outcomes and MeasuresIncident AF confirmed by medical record review.ResultsA 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 RelevanceIn 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.

Negative emotions have been linked to the development of atrial fibrillation (AF), and positive effect may be protective. However, there are few large-scale studies examining the association between psychosocial stressors that may provoke these emotions and the occurrence of AF. We examined the cross-sectional relation between psychosocial stress and AF in 24,809 women participating in the Women's Health Study. Participants answered questions about work stress (e.g., excessive work, conflicting demands), work-family spillover stress (e.g., too stressed after work to participate in activities with family), financial stress (e.g., difficulty paying monthly bills), traumatic life events (e.g., death of a child), everyday discrimination (e.g., less respect, poor service), intimate partner stress (e.g., how judgmental is your spouse/partner), neighborhood stress (e.g., neighborhood safety, trust), negative life events within 5 years (e.g., life threatening illness, legal problems), and cumulative stress (a weighted measure of the stress domains). The prevalence of confirmed AF was 3.84% (N = 953) and risk factor profiles differed by AF status. Women with AF reported significantly higher financial stress, traumatic life events, and neighborhood stress (p < 0.05). Only traumatic life events (odds ratio 1.37, 95% confidence interval 1.19 to 1.59) was significantly associated with AF after adjustment for cardiovascular risk factors, socioeconomic and psychosocial status. These large-scale cross-sectional data thus indicate a potential relationship between traumatic life events and AF in older women.

Background: To clarify the mechanisms underlying physical activity (PA)-related cardioprotection, we examined the association of PA with plasma bioactive lipids (BALs) and cardiovascular disease (CVD) events. We additionally performed genome-wide associations. Methods: PA-bioactive lipid associations were examined in VITAL (VITamin D and OmegA-3 TriaL)-clinical translational science center (REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01169259; N=1032) and validated in JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)-NC (REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00239681; N=589), using linear models adjusted for age, sex, race, low-density lipoprotein-cholesterol, total-C, and smoking. Significant BALs were carried over to examine associations with incident CVD in 2 nested CVD case-control studies: VITAL-CVD (741 case-control pairs) and JUPITER-CVD (415 case-control pairs; validation). Results: We detected 145 PA-bioactive lipid validated associations (false discovery rate <0.1). Annotations were found for 6 of these BALs: 12,13-diHOME, 9,10-diHOME, lysoPC(15:0), oxymorphone-3b-D-glucuronide, cortisone, and oleoyl-glycerol. Genetic analysis within JUPITER-NC showed associations of 32 PA-related BALs with 22 single-nucleotide polymorphisms. From PA-related BALs, 12 are associated with CVD. Conclusions: We identified a PA-related bioactive lipidome profile out of which 12 BALs also had opposite associations with incident CVD events.