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 $\pm$ 0.020 and an area under the precision-recall curve (AUPRC) of 0.890 $\pm$ 0.015, compared with an AUROC of 0.826 $\pm$ 0.023 and an AUPRC of 0.826 $\pm$ 0.022 for structural radiomics, the strongest baseline. CARDINAL also achieved the highest survival concordance index (C-index), 0.753 $\pm$ 0.015, and high-versus-low risk-tertile hazard ratio, 10.78 $\pm$ 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.

Federated Deep Learning for Privacy-Preserving Cardiovascular Disease Risk Prediction

Cardiovascular disease risk prediction models often rely on data from a single institution or centrally pooled datasets. Extending these models across institutions could be limited by privacy regulations and constraints on sharing patient-level data. Federated learning enables collaborative model development without transferring sensitive patient data, but its application in healthcare remains challenging because datasets often differ in size, population characteristics, and outcome definitions. In this study, we present a federated deep learning approach for privacy-preserving cardiovascular disease risk prediction that integrates two population-based cohorts with different characteristics: Lifelines, including 148,230 participants meeting the study inclusion criteria with self-reported outcomes, and the Rotterdam Study, including a smaller cohort of 10,155 participants with digitally linked clinical outcomes. Model performance was primarily evaluated on the Rotterdam Study because of its complete follow-up. Deep survival models trained using federated learning achieved higher predictive performance than models trained locally without federation. For the Rotterdam Study, the C-statistic increased from 0.728 (95% CI: 0.717-0.739) to 0.739 (95% CI: 0.728-0.749). For Lifelines, the C-statistic increased from 0.783 (95% CI: 0.775-0.791) to 0.787 (95% CI: 0.780-0.792). These findings suggest that federated deep learning across heterogeneous cohorts can improve cardiovascular disease risk prediction while preserving the privacy of individual-level patient data.

Privacy-Preserving Federated Learning via Differential Privacy and Homomorphic Encryption for Cardiovascular Disease Risk Modeling

Protecting sensitive health data while enabling collaborative analysis is a central challenge in healthcare. Traditional machine learning (ML) requires institutions to pool anonymized patient records, centralizing analytical development and privacy risks at a single site. Privacy-enhancing technologies (PETs), including Differential Privacy (DP) and Homomorphic Encryption (HE), can mitigate these risks. However, they are mainly studied in conventional data-sharing settings and often introduce trade-offs, including reduced model utility, higher computational cost, and increased implementation complexity. Federated Learning (FL) reduces data centralization by enabling institutions to train models locally and share only model updates. Nevertheless, FL does not eliminate privacy risks, as shared parameters or gradients may still reveal sensitive information. Integrating DP or HE into FL can strengthen privacy guarantees, yet their comparative performance and deployment implications in real-world healthcare settings remain unclear. We systematically evaluated DP and HE integration in FL under real-world conditions, comparing them with standard FL and centralized ML (cML) to quantify privacy-utility trade-offs in multi-institutional settings. Using nationwide Swedish healthcare data, we evaluated cardiovascular disease risk prediction using logistic regression (LR) and neural network (NN) learners. FL with HE achieved performance comparable to cML but introduced measurable cryptographic overhead, particularly in the NN implementation. FL with DP incurred lower computational cost; however, LR was more sensitive to calibrated noise than the NN, resulting in greater performance degradation. Our findings provide practical guidance for deploying privacy-preserving FL in fragmented healthcare systems.