Aims. To develop a deep-learning based system for recognition of subclinical atherosclerosis on a plain frontal chest x-ray. Methods and Results. A deep-learning algorithm to predict coronary artery calcium (CAC) score (the AI-CAC model) was developed on 460 chest x-ray (80% training cohort, 20% internal validation cohort) of primary prevention patients (58.4% male, median age 63 [51-74] years) with available paired chest x-ray and chest computed tomography (CT) indicated for any clinical reason and performed within 3 months. The CAC score calculated on chest CT was used as ground truth. The model was validated on an temporally-independent cohort of 90 patients from the same institution (external validation). The diagnostic accuracy of the AI-CAC model assessed by the area under the curve (AUC) was the primary outcome. Overall, median AI-CAC score was 35 (0-388) and 28.9% patients had no AI-CAC. AUC of the AI-CAC model to identify a CAC>0 was 0.90 in the internal validation cohort and 0.77 in the external validation cohort. Sensitivity was consistently above 92% in both cohorts. In the overall cohort (n=540), among patients with AI-CAC=0, a single ASCVD event occurred, after 4.3 years. Patients with AI-CAC>0 had significantly higher Kaplan Meier estimates for ASCVD events (13.5% vs. 3.4%, log-rank=0.013). Conclusion. The AI-CAC model seems to accurately detect subclinical atherosclerosis on chest x-ray with elevated sensitivity, and to predict ASCVD events with elevated negative predictive value. Adoption of the AI-CAC model to refine CV risk stratification or as an opportunistic screening tool requires prospective evaluation.

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