## 2 Materials and Methods  
### Data Description  
We analyzed a dataset collected by the DD Clinic foundation of Caserta in Italy between September 2014 and February 2020. The DD Clinic foundation is a research institute and consists of 13 sections distributed throughout the Italian territory. The main research activities, carried out in collaboration with universities and public and/or private health organisations, are in the field of oncological, neurodegenerative and cardiovascular diseases. In this study, 90 patients with a CVD diagnosis were enrolled; they signed an informed and underwent a HSHA test to evaluate the concentrations of 27 heavy metals in their hair. The analysed subjects are Caucasians (55 males and 39 females) with median age of \(53.5\pm 6.4\) years. In addition, every subject underwent a genomic analysis from which we selected SNPs of 25 genes linked to a CVD phenotype. Specifically, the genetic analysis is a nutrigenomic test and consists of a salivary swab to highlight genetic mutation that can cause metabolism alterations and the onset of several cardiovascular diseases. We implemented an allelic discrimination analysis using polymerase chain reaction (PCR) [34]. The enrolled subjects lived near the so called 'Land of Fire' (in Italian: Terra dei Fuochi)--a defined geographical area around the cities of Salerno and Naples in Campania. This area contains the largest illegal waste dump in Europe [35]. The 52 features used in our analysis (27 heavy metals and 25 SNPs) are listed in Table 1. According to the patients' clinical conditions, a three-level risk index was assigned to each subject: moderate (MR), high (HR) and very high risk (VHR). These levels are characterized by the same pathologies (heart attack, thrombosis, stroke, etc. ), the difference is linked to the severity of the clinical conditions in terms of disability and risk of mortality. Further information is reported in Table 2. Specifically, the analysed dataset was composed of:  
* 34 subjects in Class MR;
* 18 subjects in Class HR;
* 38 subjects in Class VHR. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multicolumn{4}{c}{**Heavy Metals**} \\ \hline Aluminum & Arsenic & Barium & Beryllium \\ \hline Bismuth & Boron & Cadmium & Calcium \\ \hline Chromium & Cobalt & Copper & Iron \\ \hline Lead & Lithium & Magnesium & Manganese \\ \hline Mercury & Molybdenum & Nickel & Phosphorus \\ \hline Platinum & Selenium & Sodium & Thallium \\ \hline Titanium & Vanadium & Zinc & \\ \hline \multicolumn{4}{c}{**Polymorphisms**} \\ \hline IL10 A1082G & TNF a/G-308A & CBS T1080C & IL-19C-551T \\ \hline IL4R 190A/G & BCO1 & VDR & ACE \\ \hline IL-1\(\alpha\)-899 (+84845) C\(>\)T & GSTM1 & IL-6 (-174)G/C & BHMT (GA AA AG) \\ \hline MTFR CBS C6997 & MTR A2756G & MTR A66G & BHMT (GG AA) \\ \hline IL6 634C/G and 174C/G & IL6R \(>\) Asp358 Ala; rs2228145 A\(>\)C & MNSOD2 & MNSOD3 \\ \hline MTHFR C677T & MTHFR A1298C & IFN6 874T/A & AHCY 257A/G \\ \hline CAT C262T & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: List of analysed heavy metals and selected SNPs used as features in our analysis. The heavy metal concentrations are extracted by means of TMA hair tests.