CARDINAL Predicts Cardiovascular Risk From Non-contrast Cardiac CT

Cardiovascular risk prediction remains limited by incomplete clinical data and imaging biomarkers that reduce computed tomography (CT) to a small number of handcrafted features. We developed CARDINAL (Cardiovascular Assessment via Representation learning from Deep Imaging with Nested Anatomical Latent embeddings), a clinically grounded framework that learns compact representations from routine non-contrast cardiac CT for major adverse cardiovascular event (MACE) prediction. In 17,659 patients, CARDINAL was evaluated for 1-, 3-, 5-, and 10-year MACE prediction against American Heart Association (AHA) pooled cohort equations (PCE), AHA predicting risk of cardiovascular disease events (PREVENT), coronary artery calcium (CAC), segmentation-derived CT biomarkers, and 70-feature structural radiomics. Gains were largest at longer horizons. At 10 years, CARDINAL (joint) achieved an area under the receiver operating characteristic curve (AUROC) of 0.866 ± 0.020 and an area under the precision-recall curve (AUPRC) of 0.890 ± 0.015, compared with an AUROC of 0.826 ± 0.023 and an AUPRC of 0.826 ± 0.022 for structural radiomics, the strongest baseline. CARDINAL also achieved the highest survival concordance index (C-index), 0.753 ± 0.015, and high-versus-low risk-tertile hazard ratio, 10.78 ± 3.16, with favorable reclassification and exploratory calibration. These findings suggest that non-contrast cardiac CT contains prognostic information beyond conventional risk equations, CAC scoring, and engineered imaging biomarkers.