Impact of coronary artery calcium score on the risk prediction for ischemic stroke in patients with atrial fibrillation

Background The vascular component of the CHA2DS2-VASc score reflects the presence of significant coronary artery disease on angiography or cardiac imaging as a contributor to stroke and thromboembolic risk in patients with atrial fibrillation (AF). However, this measure mainly captures the stenotic burden and may underestimate the overall coronary atherosclerosis state, particularly coronary calcification. Purpose This study aims to demonstrate the association of cardiac artery calcium score (CACS) and the risk of ischemic stroke in patients with AF. Methods Among 14,965 patients who underwent cardiac computed tomography between 2006 and 2025, a total of 1,347 patients were included who have AF without history of myocardial infarction, angina and previous percutaneous coronary intervention. The primary endpoint was the 3-year incidence of ischemic stroke stratified by CACS: minimal (0-9), mild (10-99), moderate (100-399), and severe (400-). To mitigate confounding, inverse probability weighting was applied. Results Adjusted hazard ratios (HRs) for the primary end-point stratified by CACS were mild 1.66 (95% CI, 0.86–3.20; p = 0.132); moderate 2.85 (95% CI, 1.45–5.58; p = 0.002); severe 2.13 (95% CI, 1.03–4.39; p = 0.041). Survival curves can be clustered into the two groups: minimal-mild (log-rank p = 1.000), moderate-severe (log-rank p = 1.000), with a significant divergence between mild and moderate (log-rank P = 0.048). In the subgroup with insignificant coronary stenosis (<50%), moderate to severe CACS (≥ 100) remained significantly associated with ischemic stroke (HR 2.27, [95% CI, 1.45-3.54]; p < 0.001). Overall, moderate to severe CACS (HR 1.56, [95% CI, 1.08-2.24; p = 0.017]) was comparable to the risk levels of the CHA2DS2-VASc age 65-74 component (HR 2.01, [95% CI, 1.09-3.70]; p = 0.025); Wald p = 0.530). Conclusion CACS more than 100 was independently associated with increased 3-year ischemic stroke risk in patients with AF, with a magnitude comparable to the age 65-74 component of the CHA2DS2-VASc score, suggesting potential consideration as an additional risk marker for stroke prediction in AF.