Random forests highlight the combined effect of environmental heavy metals exposure and genetic damages for cardiovascular diseases

Heavy metals are a dangerous source of pollution due to their toxicity, permanence in the environment and chemical nature. It is well known that long-term exposure to heavy metals is related to several chronic degenerative diseases (cardiovascular diseases, neoplasms, neurodegenerative syndromes, etc.). In this work, we propose a machine learning framework to evaluate the severity of cardiovascular diseases (CVD) from Human scalp hair analysis (HSHA) tests and genetic analysis and identify a small group of these clinical features mostly associated with the CVD risk. Using a private dataset provided by the DD Clinic foundation in Caserta, Italy, we cross-validated the classification performance of a Random Forests model with 90 subjects affected by CVD. The proposed model reached an AUC of 0.78 ± 0.01 on a three class classification problem. The robustness of the predictions was assessed by comparison with different cross-validation schemes and two state-ofthe-art classifiers, such as Artificial Neural Network and General Linear Model. Thus, is the first work that studies, through a machine learning approach, the tight link between CVD severity, heavy metal concentrations and SNPs. Then, the selected features appear highly correlated with the CVD phenotype, and they could represent targets for future CVD therapies.