Cardiovascular Risk Prediction

Cardiovascular disease (CVD) remains the leading cause of death among women, yet cardiovascular risk assessment often relies on clinical variables that may be missing, outdated, or unavailable in routine care. Screening mammography offers an opportunity for opportunistic cardiovascular risk stratification because it is routinely acquired and contains vascular features, including breast arterial calcifications (BAC), that are associated with cardiovascular risk and events. We evaluate whether mammography specific foundation models, originally pretrained for breast cancer-related tasks, can transfer to cardiovascular risk prediction without cardiovascular specific supervision or explicit BAC annotation. We constructed a 5-year major adverse cardiovascular event (MACE) cohort of 22,497 women linked to electronic health record outcomes, including 500 events (2.22% prevalence). The foundation models achieved AUROCs of 0.823 and 0.822 substantially exceeding an age-only model (AUROC 0.765), despite using only the screening mammogram as input, with no clinical variables. Both foundation models evaluated assigned substantially higher predicted risk to patients with radiologist-documented BAC, despite BAC never being used as a training label, and showed activation patterns consistent with vascular findings. Together, these findings suggest that mammography foundation models can recover clinically relevant cardiovascular risk information directly from mammographic pixels and suggest that screening mammography may provide an opportunistic source of cardiovascular risk information to complement conventional clinical assessment without additional imaging. Code is available in https://github.com/PauFeld/MammoCVD

This study introduces an intelligent framework that integrates machine learning and deep neural network ensemble techniques for early detection and prognosis of cardiovascular diseases. The system utilizes real-time physiological data collected from Internet of Medical Things (IoMT) devices, including ECG sensors, heart rate monitors, and blood pressure trackers. To ensure the accuracy and reliability of input data, preprocessing steps such as noise reduction, normalization, and missing value imputation are employed. The most significant health indicators are identified through effective feature selection methods and then processed using optimized classifiers such as Support Vector Machines (SVM), Random Forests, and eXtreme Gradient Boosting (XGBoost), which are combined in an ensemble architecture to improve diagnostic precision. The framework demonstrates remarkable performance in predicting cardiovascular disease risk, achieving higher accuracy, reduced false positives, and enhanced consistency compared to conventional methods. It is designed on a cloud-based infrastructure that ensures scalability and real-time processing for continuous patient monitoring. Experimental evaluation on real-world cardiovascular datasets confirms the framework's efficiency in early-stage risk assessment and clinical decision support. The results highlight the potential of combining traditional machine learning and deep learning paradigms to achieve proactive healthcare management and improve patient outcomes.

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.

Electrocardiograms (ECGs) are widely used for cardiovascular risk prediction, yet models often fail to transfer across hospitals because of protocol, population, and measurement differences. We benchmark cross-dataset generalization on three tasks - heart failure classification, 30-day all-cause mortality, and 30-day mortality among sinus-rhythm ECGs - using two large cohorts (MIMIC-IV and the Alberta Cohort). To reduce vendor-specific measurement mismatch, we build a harmonized, interpretable feature representation computed directly from raw waveforms: FeatureDB morphology/heart-rate-variability summaries plus compact time-frequency descriptors (autoregressive and wavelet features). We train XGBoost models on this unified feature space and evaluate with patient-disjoint internal and bidirectional external testing. We pre-specify two hypotheses: (H1) external AUROC retains at least 90% of source-site internal AUROC under transfer, and (H2) internal AUROC of the harmonized feature set stays within 10% of dataset-native machine-measurement models. Across tasks, internal AUROC is 0.79-0.82 and cross-dataset AUROC is 0.74-0.78, with larger and direction-dependent AUPRC shifts under transfer. As an exploratory benchmark, an end-to-end ConvNeXt model trained directly on raw ECG waveforms with age and sex achieves higher internal AUROC, while the harmonized representation remains competitive in relative cross-dataset transfer stability. These findings show that a consistent waveform-derived feature interface preserves performance, supports realistic external validation, and provides a transparent alternative for cross-site clinical prediction.

Cardiometabolic diseases remain among the most persistent drivers of preventable morbidity because diabetes, hypertension, and cardiovascular disease frequently co-occur and share metabolic, vascular, demographic, and behavioral determinants. Existing machine learning studies for chronic disease prediction often emphasize discrimination on a single dataset, while underreporting label leakage, calibration, temporal robustness, external transportability, and subgroup reliability. This paper presents CardioMeta, a calibrated multi-task framework for joint prediction of diabetes, hypertension, and cardiovascular disease across population survey and electronic health record (EHR) data. The study uses NHANES for population-level model development and temporal validation, and MIMIC-IV for EHR-domain evaluation under substantial distribution shift. To reduce circular label reconstruction, the primary analysis excludes disease-defining variables from the corresponding prediction heads, while a full-clinical feature setting is retained only as sensitivity analysis. CardioMeta combines a shared cardiometabolic encoder with disease-specific gated heads and post-hoc probability calibration. In the leakage-reduced temporal validation setting, the model achieved a macro-AUROC of 0.839, macro-AUPRC of 0.536, macro-F1 of 0.614, and expected calibration error of 0.024, with modest but consistent improvements over strong gradient-boosting and neural tabular baselines. External evaluation on MIMIC-IV showed clear degradation under domain shift, while limited fine-tuning partially recovered performance. The findings indicate that the principal value of multi-task cardiometabolic modeling lies not in inflated accuracy, but in reproducible leakage control, calibrated probabilities, and transparent reliability reporting across heterogeneous healthcare data sources.

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.

Cardiac magnetic resonance imaging (CMR) captures rich spatiotemporal information about ventricular structure and motion, but conventional risk models use only a few image-derived indices from selected cardiac phases. We present a latent dynamical model that encodes bi-ventricular anatomy and full-cycle cine motion as a continuous latent trajectory, using heart-rate-aware neural ordinary differential equation (ODE) dynamics and a graph-based mesh autoencoder to reconstruct anatomically consistent 3D+t ventricular motion. A covariate-conditioned prior defines the expected end-diastolic latent state, and a Cox proportional hazards model tests whether deviations from this prior predict incident heart failure. We studied 72,386 UK Biobank participants without baseline cardiovascular disease, including 367 incident heart failure events. In a held-out evaluation subset, adding the latent score to refitted pooled cohort equations improved the stratified C-index from 0.704 to 0.785, compared with 0.764 for seven established cardiac markers. Compared with non-graph and non-ODE approaches, the proposed model gave the best trade-off between reconstruction fidelity, generative realism, and downstream prognostic performance. These results suggest that continuous full-cycle modeling of ventricular motion provides informative cardiac phenotypes beyond conventional CMR summaries, while external validation in more representative patient cohorts is required before clinical risk-prediction use.

Background. Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major determinant of prognosis. Established AF risk scores rely on factors (older age, hypertension) nearly ubiquitous among patients with cardiovascular disease (CVD), offering limited stratification in this high-risk group. Most target long-term (5-10 year) rather than medium-term prediction. We developed interpretable ML models predicting AF risk over a 24-month and entire follow-up horizon in CVD patients using routinely collected hospital data. Methods. Single-center retrospective study of electronic health records from the National Research Cardiology Center (Russia) for patients aged >=18 with CVD but without pre-existing AF, hospitalized more than once between January 2012 and May 2019. A custom NLP pipeline transformed unstructured discharge reports into 73 structured features, combining a rule-based parser with transformer-based NER. Using LightAutoML we built a full model (73 features), a simple model (reduced subset), and a linear model for a bedside risk score. Performance was assessed by ROC AUC, compared with CHARGE-AF, C2HEST, MHS, and HAVOC, and interpreted via SHAP. Results. Of 80,576 records from 45,000 patients, 17,562 met inclusion criteria; 1,438 (8.19%) developed AF. The full model reached ROC AUC 0.735 (24-month) and 0.696 (entire follow-up); the simple model was nearly identical (0.725, 0.696). All non-linear models outperformed the four clinical risk scores (ROC AUC 0.53-0.64). The simple model uses 13 features and is named Pre-AF 13. SHAP identified age and left atrial volume as dominant predictors. A linear risk score (Pre-AF 9) stratified observed 24-month AF incidence from ~7% to 36%. Conclusion. Interpretable ML models built from routinely collected EHR data identify high-AF-risk CVD patients, outperforming established clinical risk scores.

Non-contrast computed tomography calcium scoring (CTCS) is widely recognized as an effective tool for cardiovascular risk stratification. This study aimed to develop a novel machine learning framework for predicting myocardial ischemia from routine non-contrast CTCS scans using quantitative coronary calcium assessment. This study analyzed 1,375 patients who underwent both non-contrast CTCS and regadenoson stress cardiac positron emission tomography myocardial perfusion imaging within one year at University Hospitals Cleveland Medical Center. A total of 74 variables, including clinical variables, Agatston score, and calcium-omics features, were evaluated. Relevant features were identified using XGBoost with Shapley Additive exPlanations (SHAP). Predictive models were trained and evaluated using 5-fold cross-validation. Among 987 patients, 89 (9%) were positive for myocardial ischemia. The final model incorporated the Agatston score, eight calcium-omics features, and age. The proposed model achieved a precision of 98.9+/-3.0%, sensitivity of 79.2+/-8.4, and F1 score of 87.7+/-5.3%. The addition of calcium-omics features significantly improved predictive performance compared with models using clinical variables alone or clinical variables with the Agatston score (p<0.05). Interestingly, the number of calcified arteries, despite being the lowest-ranked feature based on SHAP analysis, showed the strongest association with myocardial ischemia in logistic regression analysis (odds ratio: 3.63, 95% confidence interval: 2.80-4.77, p<0.00001). We developed a machine learning approach for predicting myocardial ischemia using routinely acquired non-contrast CTCS scans. Calcium-omics features provided incremental predictive value beyond conventional risk factors and Agatston scoring and may support more accessible cardiovascular risk stratification.

Carotid atherosclerosis is a major contributor to ischemic stroke and transient ischemic attack. Conventional ultrasound assessment is commonly based on intima-media thickness, plaque appearance, stenosis degree, and peak systolic velocity, but these morphology- and velocity-based indicators may not fully capture patient-specific vascular risk. This study presents AtheroFlow-XNet, a CUBS-compatible ultrasound morphology and uncertainty-aware learning baseline for carotid intima-media segmentation and preliminary risk prediction. Using the Carotid Ultrasound Boundary Study dataset, manual lumen-intima and media-adventitia boundary annotations were converted into dense intima-media masks for supervised segmentation. Clinical variables were incorporated into an auxiliary risk-prediction branch, and Monte Carlo dropout was used for uncertainty-aware inference. The model was evaluated using a patient-level train-validation-test split with 1,522 training images, 326 validation images, and 328 testing images. The proposed model achieved a Dice coefficient of 0.7930 for LI-MA mask segmentation, a segmentation loss of 0.2359, and an area under the receiver operating characteristic curve of 0.6910 for preliminary risk prediction. Qualitative results showed that predicted masks were generally aligned with manual annotations, while uncertainty maps highlighted ambiguous wall-boundary regions. These results suggest that ultrasound-derived carotid morphology can support automated wall analysis and uncertainty-aware interpretation. Since CUBS does not provide Doppler waveforms or CFD-derived hemodynamic biomarkers, this work should be interpreted as a reproducible morphology-driven baseline. Future work will incorporate Doppler-derived flow profiles, patient-specific vascular reconstruction, and CFD-based wall shear biomarkers.

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.

Coronary artery disease (CAD) remains one of the leading causes of death globally, highlighting the need for reliable predictive systems to support early diagnosis and risk assessment. While traditional machine learning models perform well on structured clinical data, large language models (LLMs) present new possibilities to interpret medical information expressed in natural language. In this work, we develop a hybrid framework that bridges structured clinical data and natural-language representations for CAD prediction. Using a publicly available dataset of 1,190 patient records with 11 clinical attributes, structured variables are converted into interpretable feature representations and synthetic clinical narratives using LLMs. A validation pipeline performs reverse extraction of clinical variables and computes a consistency score with the original records, achieving an average fidelity of 94.61%. We then evaluate four conventional machine learning models and compare their performance with LLM-based classification under zero-shot and few-shot prompting settings. We use two LLMs here, GPT and Gemini. Experimental results show that Random Forest achieves the highest accuracy. Despite this advantage, LLM-based classification remains beneficial in real-world clinical settings. This is because LLMs operate directly on natural language patient descriptions, meaning that sensitive numerical patient data such as exact lab values, blood pressure readings, and diagnostic codes are kept private. Findings suggest that combining structured clinical data with LLM-generated narratives can enable new directions for hybrid clinical prediction systems.

Hypertrophic cardiomyopathy (HCM) requires accurate risk stratification to inform decisions regarding ICD therapy and follow-up management. Current established models, such as the European Society of Cardiology (ESC) score, exhibit moderate discriminative performance. This study develops a robust, explainable machine learning (ML) risk score leveraging routinely collected echocardiographic, clinical, and medication data, typically contained within Electronic Health Records (EHRs), to predict a 5-year composite cardiovascular outcome in HCM patients. The model was trained and internally validated using a large cohort (N=1,201) from the SHARE registry (Florence Hospital) and externally validated on an independent cohort (N=382) from Rennes Hospital. The final Random Forest ensemble model achieved a high internal Area Under the Curve (AUC) of 0.85 +- 0.02, significantly outperforming the ESC score (0.56 +- 0.03). Critically, survival curve analysis on the external validation set showed superior risk separation for the ML score (Log-rank p = 8.62 x 10^(-4) compared to the ESC score (p = 0.0559). Furthermore, longitudinal analyses demonstrate that the proposed risk score remains stable over time in event-free patients. The model high interpretability and its capacity for longitudinal risk monitoring represent promising tools for the personalized clinical management of HCM.

Coronary artery disease, a leading cause of cardiovascular mortality worldwide, can be assessed non-invasively by coronary computed tomography angiography (CCTA). Although deep learning has advanced automated CCTA analysis, clinical translation remains constrained by the scarcity of expert-annotated data and by the spatial sparsity of coronary pathology, which occupies only a small fraction of each scan. Widely used label-free pretraining strategies, such as masked image modeling and contrastive learning, optimize for global anatomical reconstruction and tend to under-represent these tiny localized pathological features. Here we present CORA, an annotation-efficient model for comprehensive coronary artery disease assessment. Rather than reconstructing background anatomy, CORA learns from volumetric CCTA through a synthesis-driven self-supervised strategy: an anatomy-guided engine inserts diverse synthetic calcified and non-calcified lesions into unlabeled scans, reframing pretraining as an abnormality-detection task that biases representation learning toward clinically relevant disease features. We pretrained CORA on 10,138 unlabeled CCTA volumes and evaluated it across datasets from nine independent hospitals. Across plaque characterization, stenosis detection, and coronary artery segmentation, CORA consistently outperformed strong self-supervised pretraining baselines, with the largest gains on external multi-center data, indicating robust generalization under distributional shift. Coupling the imaging encoder with structured clinical variables further enabled near-term major adverse cardiac event (MACE) risk stratification. Our results show that pathology-centric, synthesis-driven pretraining is an effective and scalable strategy for annotation-efficient coronary artery disease assessment from CCTA.

To overcome the limitations of manual administrative coding in geriatric Cardiovascular Risk Management, this study introduces an automated classification framework leveraging unstructured Electronic Health Records (EHRs). Using a dataset of 3,482 patients, we benchmarked three distinct modeling paradigms on longitudinal Dutch clinical narratives: classical machine learning baselines, specialized deep learning architectures optimized for large-context sequences, and general-purpose generative Large Language Models (LLMs) in a zero-shot setting. Additionally, we evaluated a late fusion strategy to integrate unstructured text with structured medication embeddings and anthropometric data. Our analysis reveals that the custom Transformer architecture outperforms both traditional methods and generative \acs{llm}s, achieving the highest F1-scores and Matthews Correlation Coefficients. These findings underscore the critical role of specialized hierarchical attention mechanisms in capturing long-range dependencies within medical texts, presenting a robust, automated alternative to manual workflows for clinical risk stratification.

Accurate cardiovascular risk prediction is crucial for preventive healthcare; however, the development of robust Artificial Intelligence (AI) models is hindered by the fragmentation of clinical data across institutions due to stringent privacy regulations. This paper presents a comprehensive architectural case study validating the engineering robustness of FedCVR, a privacy-preserving Federated Learning framework applied to heterogeneous clinical networks. Rather than proposing a new theoretical optimizer, this work focuses on a systems engineering analysis to quantify the operational trade-offs of server-side adaptive optimization under utility-prioritized Differential Privacy (DP). By conducting a rigorous stress test in a high-fidelity synthetic environment that reflects the feature space and clinical context of real-world datasets (Framingham, Cleveland), we systematically evaluate the system's resilience to statistical noise. The validation results demonstrate that integrating server-side momentum as a temporal denoiser enables the architecture to achieve a stable F1 score of 0.78 and an Area Under the Curve (AUC) of 0.96 under the operational privacy budget (epsilon approximately 13.4), compared to a non-private baseline with an F1 score of 0.84. FedCVR statistically outperforms standard stateless baselines (FedAvg, FedProx) and other adaptive optimizers (FedAdagrad, FedYogi) under identical privacy constraints. Our findings confirm that server-side adaptivity is a structural prerequisite for recovering clinical utility under realistic privacy budgets, providing a validated engineering blueprint for secure multi-institutional collaboration.

Cardiovascular disease (CVD) remains one of the leading global health challenges, accounting for more than 19 million deaths worldwide. To address this, several tools that aim to predict CVD risk and support clinical decision making have been developed. In particular, the Framingham Risk Score (FRS) is one of the most widely used and recommended worldwide. However, it does not explain why a patient was assigned to a particular risk category nor how it can be reduced. Due to this lack of transparency, we present a logical explainer for the FRS. Based on first-order logic and explainable artificial intelligence (XAI) fundaments, the explainer is capable of identifying a minimal set of patient attributes that are sufficient to explain a given risk classification. Our explainer also produces actionable scenarios that illustrate which modifiable variables would reduce a patient's risk category. We evaluated all possible input combinations of the FRS (over 22,000 samples) and tested them with our explainer, successfully identifying important risk factors and suggesting focused interventions for each case. The results may improve clinician trust and facilitate a wider implementation of CVD risk assessment by converting opaque scores into transparent and prescriptive insights, particularly in areas with restricted access to specialists.

Cardiovascular disease is the primary cause of death globally, necessitating early identification, precise risk classification, and dependable decision-support technologies. The advent of large language models (LLMs) provides new zero-shot and few-shot reasoning capabilities, even though machine learning (ML) algorithms, especially ensemble approaches like Random Forest, XGBoost, LightGBM, and CatBoost, are excellent at modeling complex, non-linear patient data and routinely beat logistic regression. This research predicts cardiovascular disease using a merged dataset of 1,190 patient records, comparing traditional machine learning models (95.78% accuracy, ROC-AUC 0.96) with open-source large language models via OpenRouter APIs. Finally, a hybrid fusion of the ML ensemble and LLM reasoning under Gemini 2.5 Flash achieved the best results (96.62% accuracy, 0.97 AUC), showing that LLMs (78.9 % accuracy) work best when combined with ML models rather than used alone. Results show that ML ensembles achieved the highest performance (95.78% accuracy, ROC-AUC 0.96), while LLMs performed moderately in zero-shot (78.9%) and slightly better in few-shot (72.6%) settings. The proposed hybrid method enhanced the strength in uncertain situations, illustrating that ensemble ML is considered the best structured tabular prediction case, but it can be integrated with hybrid ML-LLM systems to provide a minor increase and open the way to more reliable clinical decision-support tools.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, yet early risk detection is often limited by available diagnostics. Carotid ultrasound, a non-invasive and widely accessible modality, encodes rich structural and hemodynamic information that is largely untapped. Here, we present a machine learning (ML) framework that extracts clinically meaningful representations of vascular damage (VD) from carotid ultrasound videos, using hypertension as a weak proxy label. The model learns robust features that are biologically plausible, interpretable, and strongly associated with established cardiovascular risk factors, comorbidities, and laboratory measures. High VD stratifies individuals for myocardial infarction, cardiac death, and all-cause mortality, matching or outperforming conventional risk models such as SCORE2. Explainable AI analyses reveal that the model relies on vessel morphology and perivascular tissue characteristics, uncovering novel functional and anatomical signatures of vascular damage. This work demonstrates that routine carotid ultrasound contains far more prognostic information than previously recognized. Our approach provides a scalable, non-invasive, and cost-effective tool for population-wide cardiovascular risk assessment, enabling earlier and more personalized prevention strategies without reliance on laboratory tests or complex clinical inputs.