Background Limited population-based data on the (sex-specific) link between subclinical measures of peripheral atherosclerosis and new-onset atrial fibrillation (AF) exist. Methods and Results Subclinical measures of peripheral atherosclerosis including carotid intima-media thickness (cIMT), carotid plaque, and ankle-brachial index (ABI) were assessed at baseline and follow-up examinations. A total of 12 840 participants free of AF at baseline from the population-based Rotterdam Study were included. Cox proportional hazards models and joint models, adjusted for cardiovascular risk factors, were used to determine the associations between baseline and longitudinal measures of cIMT, carotid plaque, and ABI with new-onset AF. During a median follow-up of 9.2 years, 1360 incident AF cases occurred among 12 840 participants (mean age 65.2 years, 58.3% women). Higher baseline cIMT (fully-adjusted hazard ratio [HR], 95% CI, 1.81, 1.21-2.71; P=0.0042), presence of carotid plaque (fully-adjusted HR, 95% CI, 1.19, 1.04-1.35; P=0.0089), lower ABI (fully-adjusted HR, 95% CI, 1.57, 1.14-2.18; P=0.0061) and longitudinal measures of higher cIMT (fully-adjusted HR, 95% CI, 2.14, 1.38-3.29; P=0.0021), presence of carotid plaque (fully-adjusted HR, 95% CI, 1.61, 1.12-2.43; P=0.0112), and lower ABI (fully-adjusted HR, 95% CI, 4.43, 1.83-10.49; P=0.0007) showed significant associations with new-onset AF in the general population. Sex-stratified analyses showed that the associations for cIMT, carotid plaque, and ABI were mostly prominent among women. Conclusions Baseline and longitudinal subclinical measures of peripheral atherosclerosis (carotid atherosclerosis, and lower extremity peripheral atherosclerosis) were significantly associated with an increased risk of new-onset AF, especially among women. Registration URL: https://www.trialregister.nl, https://www.apps.who.int/trialsearch/; Unique identifier: NL6645/NTR6831.
Keywords: atrial fibrillation; epidemiology; peripheral atherosclerosis; risk factors; sex‐differences.