Association between atherosclerosis and atrial fibrillation progression in patients with paroxysmal atrial fibrillation: Data from the RACE V study

Background Atrial fibrillation (AF) may progress from paroxysmal AF (PAF) to more persistent forms, but the underlaying mechanisms are not well understood. The aim of this study was to assess the association between atherosclerosis and AF progression in patients with PAF. Methods In this substudy of RACE V, 612 patients with PAF underwent extensive phenotyping at baseline and continuous rhythm monitoring. The association between atherosclerosis and AF progression was investigated. Results The median age was 64 (57-70) years, 257 (42%) were women, and the median CHA2DS2-VA score was 2 (1-3). At baseline, 395 (65%) patients had atherosclerosis, defined by carotid/coronary imaging and/or history of vascular disease. Patients with atherosclerosis were older, had higher waist circumference, more hypertension, and lower eGFR than patients with no atherosclerosis. During a median of 3.4 (2.8-3.7) years follow-up, 108 (18%) patients had AF progression. The presence of atherosclerosis was associated with increased progression (21% vs. 12%; p = .004). In univariable analyses, atherosclerosis was a determinant of AF progression (OR: 2.04; 95% CI: 1.28-3.37; p = .004), and the association persisted following adjustment for established risk factors (OR: 2.23; 95% CI: 1.10-4.89; p = .034). Conclusions In patients with paroxysmal AF, 65% of patients had atherosclerosis. Atherosclerosis was a determinant of AF progression after adjustment for established risk factors and comorbidities, suggesting that vascular disease may contribute directly to atrial remodelling and arrhythmia persistence. (Am Heart J 2026;296:107366.)