Mp-453085-9 sex differences in all-cause and cvd mortality associated with new-onset incident atrial fibrillation: the vital study

Conflicting data exist as to whether women with atrial fibrillation (AF) are at higher risk of adverse outcomes and mortality than men. To examine the association between a new diagnosis of AF and cardiovascular (CV) outcomes and death in women as compared to men. We prospectively examined the association between incident AF and non-fatal cardiovascular disease (CVD) (stroke, myocardial infarction, or heart failure) and CV mortality and total mortality among 12,693 women and 12,285 men without a prior history of CVD or AF from the VITAL study. Multivariable Cox proportional-hazards - models with updated time-varying covariates, and comparison test were used to assess for sex differences. During a median follow-up of 6.3 years, 459 women and 554 men developed new-onset AF. After multivariable adjustment for CVD risk factors, women with incident AF had similarly high relative risks of subsequent non-fatal CVD (HR 5.6; 95% CI, 4.1-7.6) as men (HR 4.9; 95% CI, 3.7-6.5) with no significant difference (p=0.36). In contrast, incident AF was associated with significantly higher multivariable-adjusted relative risks for subsequent CVD mortality in women (HR 6.1; 95% CI, 3.5-10.5) as compared to men (HR 2.0; 95% CI, 1.0-4.0); p, for difference= 0.01. The magnitude of the HR for the association between incident AF and total mortality was also significantly greater in women (HR 3.4; 95% CI, 2.5-4.6) as compared to men (HR 1.8; 95% CI, 1.3-2.5); p, difference= 0.005. In multivariable models that further controlled for interim non-fatal CVD events, incident AF remained significantly associated with higher risks of CVD mortality (HR 22; 95% CI, 1.3-4.0) and total mortality (HR 1.7; 95% CI 1.2-2.3) in women; however, the relative risk elevations were completely attenuated in men (HR 0.7; 95% CI 0.3-1.4 for CVD mortality; HR 1.0; 95% CI 0.7-1.4 for total mortality; p for difference 0.009 and 0.02 respectively). In a prospective cohort of women and men without baseline AF or CVD, the magnitudes of the relative risk elevations for CVD and all-cause mortality associated with incident AF were greater in women as compared to men. As opposed to men, the elevation in risk persisted for women even after controlling for interim CVD events, suggesting that other factors beyond interim CVD events account for the elevated mortality risk associated with AF in women.