Left Atrial Enlargement Identifies Risk of Stroke Independent of Atrial Fibrillation

Background Left atrial (LA) enlargement has been proposed to increase stroke risk independent of atrial fibrillation (AF), but evidence accounting for AF over time is limited. We tested whether the association between LA enlargement and stroke persist independent of new‐onset AF. Methods In this observational study, participants from the Copenhagen General Population Study underwent cardiac computed tomography from 2010 through 2018 and were followed until December 2022. LA volume was indexed to body surface area. LA enlargement was defined using sex‐specific cutoffs. The primary outcome was incident stroke. Secondary outcomes were incident AF, heart failure, dementia, and all‐cause mortality. Individuals with baseline AF were excluded. Hazard ratios (HRs) were estimated using cause‐specific Cox models with AF modeled as a time‐varying covariate. Results Among 10 024 individuals (mean age 60 years, 57% women), 684 (6.8%) had LA enlargement. Over a median follow‐up of 7.3 years stroke occurred in 356 individuals (3.6%). LA enlargement was associated with a higher absolute risk of stroke (11.1% versus 4.6%, risk difference 6.5% [95% CI, 2.4–10.6]) and an increased hazard (adjusted HR, 1.49 [95% CI, 1.09–2.05]; P =0.013), which remained similar after adjustment for incident AF, and in separate models using the CHA 2 DS 2 ‐VA score and P‐wave terminal force in lead V1. LA enlargement was also associated with higher risk of AF (HR, 3.77 [95% CI, 3.00–4.73]) and heart failure (HR, 3.59 [95% CI, 2.54–5.06]) but not with dementia or all‐cause mortality. Conclusions LA enlargement was associated with incident stroke independent of incident AF, supporting LA enlargement as a marker of thromboembolic risk.