Abstract
BACKGROUND: Environmental exposure to heavy metals, such as arsenic, cadmium, and lead, is a known risk factor for cardiovascular diseases. OBJECTIVE: We aim to examine the associations between heavy metal exposure and the mortality of patients with cardiovascular diseases. METHODS: We analyzed data from the NHANES 2003-2018, including urine and blood metal concentrations from 4,924 participants. Five machine learning models-CoxPHSurvival, FastKernelSurvivalSVM, GradientBoostingSurvival, RandomSurvivalForest, and ExtraSurvivalTrees-were used to predict cardiovascular mortality. Model performance was assessed with the concordance index (C-index), integrated Brier score, time-dependent AUC, and calibration curves. SHAP analysis was conducted using a reduced background dataset created via K-means clustering. RESULTS: GradientBoostingSurvival (GBS) showed the best performance for hypertension (C-index: 0.780, mean AUC: 0.798). RandomSurvivalForest (RSF) was the top model for coronary heart disease (C-index: 0.592, mean AUC: 0.626) and myocardial infarction (C-index: 0.705, mean AUC: 0.743), while CoxPHSurvival excelled for heart failure (C-index: 0.642, mean AUC: 0.672) and stroke (C-index: 0.658, mean AUC: 0.691). ExtraSurvivalTrees performed best in angina (C-index: 0.652, mean AUC: 0.669). Calibration curves confirmed the models' accuracy. SHAP analysis identified age as the most influential factor, with heavy metals like lead, cadmium, and thallium significantly contributing to risk. A user-friendly web calculator was developed for individualized survival predictions. CONCLUSION: Machine learning models, including GradientBoostingSurvival, RandomSurvivalForest, CoxPHSurvival, and ExtraSurvivalTrees, demonstrated strong performance in predicting mortality risk for various cardiovascular diseases. Key metals were identified as significant risk factors in cardiovascular risk assessment.