Cardiovascular

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.

TL;DR

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, particularly among individuals with dyslipidemia.

Key Findings

CVD patients differed from controls in age, education level, and residential area.

  • CVD patients were older on average (mean age 52.8 years vs. 45.8 years in controls)
  • CVD patients had higher rates of illiteracy (65.3% vs. 44% in controls)
  • CVD patients were more likely to live in rural areas compared to controls
  • The study recruited 150 CVD cases and 150 controls from the Kurdish population in the Ravansar region of western Iran

CVD patients with elevated lipid levels had higher serum arsenic and lower serum chromium compared to controls.

  • CVD patients with elevated TC, TG, and LDL/HDL ratio had higher levels of As compared to controls
  • CVD patients with elevated TC, TG, and LDL/HDL ratio had lower levels of Cr compared to controls
  • Levels of essential elements (Zn, Cu, Fe) were comparable between CVD cases and controls
  • Serum element levels were measured using inductively coupled plasma mass spectrometry (ICP-MS)

Arsenic exposure was independently associated with significantly increased CVD risk among participants with elevated total cholesterol.

  • Among participants with elevated TC, OR for CVD associated with second quartile of As: 7.05 (95% CI: 3.19–16.3; p < 0.001)
  • Third quartile of As: OR 3.54 (95% CI: 1.65–7.83; p = 0.001)
  • Fourth quartile of As: OR 3.33 (95% CI: 1.55–7.37; p = 0.002), all compared to the first (reference) quartile
  • These associations remained statistically significant after simultaneous adjustment for all measured metals using Firth correction (Model 2)

Nickel exposure was independently associated with increased CVD risk in fully adjusted models.

  • Among participants with elevated TC, OR for CVD in the third quartile of Ni: 15.6 (95% CI: 6.59–40.3; p < 0.001)
  • Fourth quartile of Ni: OR 2.83 (95% CI: 1.30–6.35; p = 0.001), compared to the first quartile
  • Ni remained independently associated with elevated CVD risk after simultaneous adjustment for all measured metals (Model 2 with Firth correction)
  • Along with As, Ni was one of only two metals to retain statistical significance in fully adjusted multi-metal models

Mercury and iron showed associations with CVD risk in single-metal models but these associations were not independent after full adjustment for co-exposures.

  • In single-metal models adjusted for potential confounders, higher quartiles of Fe and Hg were associated with increased CVD risk
  • After simultaneous adjustment for all measured metals (Model 2 with Firth correction), associations for Hg and Fe were attenuated and no longer statistically significant
  • Hg and Fe were therefore not identified as independent risk factors for CVD in this population
  • This finding highlights the importance of considering mixed-metal exposures when evaluating cardiovascular risk

Higher serum zinc and chromium levels were associated with reduced CVD risk.

  • 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
  • These inverse associations were observed among individuals with elevated lipid profiles
  • The protective associations for Zn and Cr persisted in adjusted models
  • These findings suggest essential elements may play a protective role in cardiovascular health, particularly among individuals with dyslipidemia

The study population was drawn from a Kurdish cohort in western Iran with samples collected between August and December 2023.

  • A total of 300 participants were recruited: 150 CVD cases and 150 controls
  • Participants were from the Ravansar Non-Communicable Diseases (RaNCD) study
  • Blood samples were received from the Ravansar Cohort Biobank between August 2023 and December 2023
  • Logistic regression models assessed CVD risk by comparing the second, third, and fourth quartiles of elemental concentrations with the first quartile
  • Blood concentrations of TC, TG, HDL, and LDL were measured in all participants alongside serum trace elements

What This Means

This research suggests that exposure to certain toxic metals — specifically arsenic and nickel — is independently linked to a higher risk of cardiovascular disease (CVD) in adults, especially those who already have elevated blood lipid levels (such as high cholesterol or triglycerides). The study was conducted in western Iran among Kurdish adults, comparing 150 people with CVD to 150 people without the disease. Even after accounting for other metals and confounding factors, arsenic and nickel stood out as significant risk factors. In contrast, two essential minerals — zinc and chromium — were associated with a lower risk of CVD, suggesting they may have a protective effect on heart health. The study also found that mercury and iron appeared linked to CVD risk when examined individually, but these associations disappeared when all metals were analyzed together. This highlights an important methodological point: looking at metals one at a time can give a misleading picture of cardiovascular risk if people are simultaneously exposed to multiple metals, as is typically the case in real-world environments. CVD patients in this study were also older, less educated, and more likely to live in rural areas than controls, suggesting that social and demographic factors also play a role. This research suggests that environmental exposure to toxic metals like arsenic and nickel may be an underappreciated contributor to heart disease risk, particularly in populations with dyslipidemia. It also points to a potentially beneficial role for adequate zinc and chromium levels in cardiovascular health. These findings may be relevant to public health efforts in regions with elevated environmental metal exposures, and they underscore the need to consider the combined effects of multiple metal exposures rather than evaluating each in isolation.

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Citation

Nakhaee S, Azadi N, Tinkov A, Sharafi K, Mahjoubian M, Mansouri B. (2026). 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 toxicology. https://doi.org/10.1007/s12012-026-10190-z