Risk of Malignant Cancer Among Women With New-Onset Atrial Fibrillation.

Importance: A substantial proportion of patients with atrial fibrillation (AF) die of noncardiovascular causes, and recent studies suggest a link between AF and cancer.

Objective: To evaluate the associations between AF and cancer in a large, long-term prospective cohort study.

Design, Setting, And Participants: In this cohort study, a total of 34 691 women 45 years or older and free of AF, cardiovascular disease, and cancer at baseline were prospectively followed up between 1993 and 2013, for incident AF and malignant cancer within the Women's Health Study, a randomized clinical trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer. Cox proportional hazards models using time-updated covariates were constructed to assess the association of new-onset AF with subsequent cancer and to adjust for potential confounders. Data analysis was performed from December 2014 to May 2015.

Exposure: New-onset AF.

Main Outcomes And Measures: Incident malignant cancer confirmed by an end point committee.

Results: During a median follow-up of 19.1 years of 34 691 study participants (interquartile range [IQR], 17.6-19.7 years), new-onset AF and malignant cancer were confirmed among 1467 (4.2%) and 5130 (14.8%) participants, respectively. Median age at baseline among participants with new-onset AF and new-onset cancer during follow-up was 58 years (IQR, 52-64 years) and 55 years (IQR, 50-61 years), respectively. Atrial fibrillation was a significant risk factor for incident cancer in age-adjusted (hazard ratio [HR], 1.58; 95% CI, 1.34-1.87; P < .001) and multivariable-adjusted (HR, 1.48; 95% CI, 1.25-1.75; P < .001) models. The relative risk of cancer was highest in the first 3 months after new-onset AF (HR, 3.54; 95% CI, 2.05-6.10; P < .001) but remained significant beyond 1 year after new-onset AF (adjusted HR, 1.42; 95% CI, 1.18-1.71; P < .001), and a trend toward an increased cancer mortality was observed (adjusted HR, 1.32; 95% CI, 0.98-1.79; P = .07). In contrast, among women with new-onset cancer, the relative risk of AF was increased only within the first 3 months (HR, 4.67; 95% CI, 2.85-7.64; P < .001) but not thereafter (HR, 1.15; 95% CI, 0.95-1.39; P = .15).

Conclusions And Relevance: In this large, initially healthy cohort, women with new-onset AF had an elevated cancer risk beyond 1 year of AF diagnosis. Shared risk factors and/or common systemic disease processes might underlie this association.