New-onset atrial fibrillation as a predictor of cancer: Insights from a real-world dataset

Abstract

Background: A bidirectional relationship between atrial fibrillation (AF) and cancer has been suggested, but the mechanisms and directionality remain poorly understood.

Objective: This study aimed to examine the relationship between new-onset AF and incident cancer across different age groups.

Methods: This retrospective study used the TriNetX research network. Patients with hypertension, type 2 diabetes, or coronary artery disease were included and stratified by the presence of AF. Individuals with previous malignancy were excluded. Patients were categorized into 3 age groups (30-50, 50-70, and 70-85 years) and matched 1:1 using propensity scores. The primary outcome was all-cause cancer incidence, with secondary analyses of site-specific malignancies. Risk ratios, Kaplan-Meier survival analysis, and multivariable Cox regression models were used. Follow-up was up to 15 years after AF diagnosis.

Results: Matched cohort sizes were 30-50 (n = 67,156 per group), 50-70 (n = 510,308), and 70-85 years (n = 882,729). AF was associated with an increased cancer risk: relative risks of 2.99, 1.79, and 1.49 across increasing age groups (all P < .001). Kaplan-Meier analyses showed decreased cancer-free survival: hazard ratios of 2.96, 1.84, and 1.53 across increasing age groups (all P < .001). Sensitivity analyses excluding cancers diagnosed within the first 3 months and after the first year of AF onset, comparing AF subtypes, and using multivariable Cox models confirmed consistent associations.

Conclusion: AF is associated with an increased risk of incident cancer, particularly in younger individuals.

Keywords: Atrial arrhythmia; Atrial fibrillation; Cancer; Cardio-oncology; Epidemiology.