An Interpretable and Externally Validated Model for Cardiovascular Disease Risk Assessment in Older Adults

Cardiovascular disease (CVD) risk assessment in older adults requires models that are accurate, clinically interpretable, and able to retain performance in independent populations. This study developed an interpretable machine-learning framework for CVD risk stratification in individuals aged 65 years and older using routinely available clinical factors and a selected biochemical extension and then evaluated its performance in a substantially larger independent external cohort. Model development used a development cohort of 100 patients (Almaty, age ≥ 65) with leakage-free nested cross-validation and out-of-fold (OOF) probabilities. Three internally evaluated configurations were compared: a clinical logistic regression baseline (LR clinical), a biomarker-augmented logistic regression (LR selected), and a nonlinear random forest on the selected feature set (RF selected). Discrimination was assessed using ROC-AUC and PR-AUC; probabilistic accuracy using Brier score and log loss. Calibration was examined using OOF calibration curves with sigmoid calibration for selected models. Decision-analytic utility and exploratory operational thresholds were assessed using Decision Curve Analysis (DCA), yielding a three-tier scale with thresholds t_low = 0.23 and t_high = 0.40. In nested cross-validation, LR clinical achieved ROC-AUC 0.9425 ± 0.0188 and PR-AUC 0.9574 ± 0.0092 with Brier 0.1004 ± 0.0215 and log loss 0.3634 ± 0.0652; LR selected performed worse, while RF selected showed competitive discrimination. External validation on an independent cohort (n = 695) showed retained discrimination (ROC-AUC 0.8355; PR-AUC 0.9376) with acceptable probabilistic accuracy (Brier 0.1131; log loss 0.3760), and recalibration (intercept + slope) slightly improved probability metrics. Explainability analyses (odds ratios, permutation importance, SHAP) consistently identified heredity, BMI, physical activity, and diabetes as influential model-associated factors, with clinically plausible directionality. The results suggest that an interpretable model trained on a small geriatric cohort can retain meaningful predictive performance on a substantially larger external cohort, supporting the potential value of transparent risk stratification in older adults, while broader prospective and multi-center validation remains necessary before routine clinical implementation.