This study aimed to examine the relationship between serum cholesterol levels and the ratio of zinc (Zn) and copper (Cu) in the blood serum and the incidence of cardiovascular disease (CVD). In Phase I of the study, 9704 individuals between the age of 35 and 65 years were recruited. Phase II of the cohort study comprised 7561 participants who completed the 10-year follow-up. The variables which were measured at the baseline of the study included gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP); biochemical parameters including serum Cu, Zn, copper-zinc ratio (Cu/Zn), zinc-copper ratio (Zn/Cu); fasted lipid profile consisting of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) as well as fasting serum glucose, and triglycerides-glucose (TyG) index. Decision tree (DT) and logical regression (LR) models were applied to examine the relationship between the aforementioned factors and CVD. CVD was diagnosed in 837 individuals (378 males and 459 females) out of 7561 participants. According to the LR models, SBP, TC, HDL, age, Zn/Cu, and TyG index for males and SBP, age, TyG index, HDL, TC, Cu/Zn, and Cu for females had the highest correlation with CVD (p-value ≤ 0.033). Based on the DT algorithm, 88% of males with SPB < 129.66 mmHg, younger age (age < 53 years), TyG index < 9.53, 173 ≤ TC < 187 mg/dL, and HDL ≥ 32 mg/dL had the lowest risk of CVD. Also, 98% of females with SBP < 128 mmHg, TyG index < 9.68, age < 44, TC < 222 mg/dL, and HDL ≥ 63.7 mg/dL had the lowest risk of CVD. It can be concluded that the Zn/Cu for men and Cu/Zn for women, along with dyslipidemia and SBP, could significantly predict the risk of CVD in this cohort from northeastern Iran.

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