The Effect of Serum Trace Element Levels On Cardiovascular Diseases in Adults in the Ravansar Region (Western Iran): A Risk Assessment Study in the Context of Elevated Lipid Profiles.

Cardiovascular diseases (CVDs) are acknowledged as a primary contributor to global human mortality, including in Iran. There is growing interest in understanding the interactions between toxic and essential elements in the body. Therefore, the objective of this research was to examine how levels of essential and toxic elements affect the risk of cardiovascular disease among individuals with elevated serum lipid levels. This case-control study was conducted using data from the Kurdish population participating in the Ravansar Non-Communicable Diseases (RaNCD) study in the Ravansar region of western Iran. Samples were received from the Ravansar Cohort Biobank between August 2023 and December 2023. A total of 300 participants were recruited, comprising 150 individuals with cardiovascular diseases (CVDs) as cases and 150 controls. Blood concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured in all participants. Serum levels of arsenic (As), mercury (Hg), nickel (Ni), cadmium (Cd), lead (Pb), zinc (Zn), copper (Cu), chromium (Cr), and iron (Fe) were determined using inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression models were used to assess the risk of CVD by comparing the second, third, and fourth quartiles of elemental concentrations with the first quartile. The results of current study showed that CVDs patients were older (mean age: 52.8 yrs vs. 45.8 yrs), less educated (65.3% vs. 44% illiterate), and mostly living in rural areas. CVDs patients with elevated levels of TC, TG, and LDL/HDL ratio had higher levels of As but lower levels of Cr as compared to controls. The levels of essential elements were comparable between the two groups. In single-metal models adjusted for potential confounders, higher quartiles of As, Ni, Fe, and Hg were associated with an increased risk of CVD among individuals with elevated TC, TG, or LDL/HDL ratio levels. However, after simultaneous adjustment for all measured metals (Model 2 with Firth correction), only As and Ni remained independently associated with elevated risk. For instance, among participants with elevated TC, the odds ratios (ORs) for CVD associated with As exposure were 7.05 (95% CI: 3.19-16.3; p < 0.001), 3.54 (95% CI: 1.65-7.83; p = 0.001), and 3.33 (95% CI: 1.55-7.37; p = 0.002) for the second, third, and fourth quartiles, respectively, compared with the reference quartile. Elevated Ni levels were also associated with an increased risk of CVD for third (15.6; 95% CI: 6.59-40.3; p < 0.001) and fourth quartile (2.83; 95% CI: 1.30-6.35; p = 0.001). The associations for Hg and Fe were attenuated and no longer statistically significant in the fully adjusted models. Conversely, higher Zn and Cr levels were associated with reduced CVD risk, with ORs below 1.0 and 95% confidence intervals that did not include 1.0. Higher blood levels of As and Ni were independently associated with an increased risk of CVD, whereas higher Cr and Zn levels were associated with a reduced risk. Although mercury and iron showed associations in single-metal models, these did not persist after adjustment for co-exposure to other metals and thus were not identified as independent risk factors in this population. These findings suggest that both toxic and essential elements may play important roles in cardiovascular health, particularly among individuals with dyslipidemia, and highlight the importance of considering mixed-metal exposures when evaluating cardiovascular risk.