Risk of Death and Cardiovascular Events in Initially Healthy Women With New-Onset Atrial Fibrillation

Context The risks associated with new-onset atrial fibrillation (AF) among middle-aged women and populations with a low comorbidity burden are poorly defined. Objectives To examine the association between incident AF and mortality in initially healthy women and to evaluate the influence of associated cardiovascular comorbidities on risk. Design, Setting, and Participants Between 1993 and March 16, 2010, 34 722 women participating in the Women's Health Study underwent prospective follow-up. Participants were 95% white, older than 45 years (median, 53 [interquartile range {IQR}, 49-59] years), and free of AF and cardiovascular disease at baseline. Cox proportional hazards models with time-varying covariates were used to determine the risk of events among women with incident AF. Secondary analyses were performed among women with paroxysmal AF. Main Outcome Measures Primary outcomes included all-cause, cardiovascular, and noncardiovascular mortality. Secondary outcomes included stroke, congestive heart failure, and myocardial infarction. Results During a median follow-up of 15.4 (IQR, 14.7-15.8) years, 1011 women developed AF. Incidence rates per 1000 person-years among women with and without AF were 10.8 (95% confidence interval [CI], 8.1-13.5) and 3.1 (95% CI, 2.9-3.2) for all-cause mortality, 4.3 (95% CI, 2.6-6.0) and 0.57 (95% CI, 0.5-0.6) for cardiovascular mortality, and 6.5 (95% CI, 4.4-8.6) and 2.5 (95% CI, 2.4-2.6) for noncardiovascular mortality, respectively. In multivariable models, hazard ratios (HRs) of new-onset AF for all-cause, cardiovascular, and noncardiovascular mortality were 2.14 (95% CI, 1.64-2.77), 4.18 (95% CI, 2.69-6.51), and 1.66 (95% CI, 1.19-2.30), respectively. Adjustment for nonfatal cardiovascular events potentially on the causal pathway to death attenuated these risks, but incident AF remained associated with all mortality components (all-cause: HR, 1.70 [95% CI, 1.30-2.22]; cardiovascular: HR, 2.57 [95% CI, 1.63-4.07]; and noncardiovascular: HR, 1.42 [95% CI, 1.02-1.98]). Among women with paroxysmal AF (n=656), the increase in mortality risk was limited to cardiovascular causes (HR, 2.94; 95% CI, 1.55-5.59). Conclusion Among a group of healthy women, new-onset AF was independently associated with all-cause, cardiovascular, and noncardiovascular mortality, with some of the risk potentially explained by nonfatal cardiovascular events. JAMA. 2011; 305(20): 2080-2087