It is frequently observed that patients with first-ever acute ischemic stroke (AIS) have a common occurrence of asymptomatic coronary artery disease (CAD). This condition is associated with a poor prognosis. Early detection and recognition of asymptomatic CAD in first-ever AIS patients may optimize the clinical management and ultimately lead to improved outcomes. The aim of this study was to investigate the role of aortic arch plaque (AAP) detected through combined computed tomography angiography (CTA) as an early predictor of asymptomatic CAD in patients with first-ever AIS without prior diagnosis of CAD.A cross-sectional study was conducted at Xuanwu Hospital, Capital Medical University from January 2019 to December 2021, involving patients with first-ever AIS caused by large arterial atherosclerosis. Patients with a history of recognized cardiovascular disease, nonatherosclerotic arterial stenosis, atrial fibrillation related to cardioembolism, and complete carotid occlusions were excluded. The study utilized a combined coronary and cervicocephalic CTA to evaluate atherosclerosis in the cervicocephalic, aortic, and coronary arteries simultaneously. First-ever AIS patients without prior diagnosis of CAD were divided into 2 groups: 1 with asymptomatic CAD detected through CTA and the other without. Multivariate logistic regression was used to identify independent risk factors associated with the presence of asymptomatic CAD, including aortic arch, cervical and intracranial atherosclerotic characteristics (e.g., vascular stenosis, plaque thickness, extent, and complexity).Among 182 AIS patients, 84 (46.2%) had asymptomatic CAD. Increased aortic arch plaque (AAP) thickness per millimeter [adjusted odds ratio (aOR): 1.26; 95% confidence interval (CI): 1.08-1.47], presence of severe AAP (aOR: 4.24; 95% CI: 1.59-12.03), mixed AAP (aOR: 2.65; 95% CI: 1.09-6.62), and ulcerative AAP (aOR: 11.76; 95% CI: 2.05-222.84) raised the risk of asymptomatic CAD in stroke patients, independent of other factors. The combination of ulcerative AAP, diabetes mellitus, and smoking could predict asymptomatic CAD with an area under the receiver operating characteristic curve (AUC) of 0.71 (95% CI: 0.64-0.79; P<0.001). Ulcerative AAP was found to be more valuable than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in first-ever AIS patients.The presence of ulcerative AAP was associated with asymptomatic CAD in first-ever AIS patients. As an early systemic atherosclerosis feature, ulcerative AAP is probably a more valuable indicator than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in AIS patients.2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.