Exposure to Toxic Heavy Metals Increases Risk for Atherosclerosis

Researchers sought to determine the individual and collective associations of toxic metal exposure with subclinical atherosclerosis in mid-life working adults.

Exposure to arsenic, cadmium, titanium, and potentially antimony increase risk for atherosclerosis, according to results of The Aragon Workers Health Study, which was published in Atherosclerosis, Thrombosis, and Vascular Biology.

For the longitudinal cohort study, researchers analyzed annual health exams (2011-2014) of 1873 Opel car assembly plant workers in Spain. Exposure to inorganic arsenic species, antimony, barium, cadmium, chromium, titanium, tungsten, uranium, and vanadium were assessed in urine samples. Using ultrasound, researchers examined the presence of plaque in the carotid, femoral, and coronary arteries. Risk for atherosclerosis was related with exposure to heavy metals.

Urine levels indicated the highest exposure was to titanium (median, 9.8 mg/g) followed by barium (median, 1.98 mg/g), arsenic (median, 1.83 mg/g), chromium (median, 1.18 mg/g), vanadium (median, 0.66 mg/g), cadmium (median, 0.27 mg/g), tungsten (median, 0.23 mg/g), antimony (median, 0.05 mg/g), and uranium (median, 0.03 mg/g).

Increased urinary metals were observed among women compared with men; older individuals compared with younger; smokers compared with never smokers; and individuals with diabetes, hypertension, or high cholesterol.

The level of chromium was correlated with antimony (Spearman correlation, 0.49) and cadmium with uranium (Spearman correlation, -0.25).

A principal component (PC) analysis found that PCI explained 34.6% of the variance and reflected the levels of arsenic, cadmium, chromium, and antimony; PC2 explained 13.5% of the variance, reflecting uranium, vanadium, and tungsten; and PC3 explained 10.1% of the variance, reflecting barium and titanium.

Plaque in the carotid artery was observed among 659 participants, in the femoral artery among 987, and in the coronary artery among 691. Any plaque associated with cadmium (adjusted odds ratio [aOR], 1.67; P =.001), titanium (aOR, 1.26; P =.02), and arsenic (aOR, 1.25; P =.02) exposure.

Carotid artery plaque associated with cadmium (aOR, 1.38; P =.02), arsenic (aOR, 1.24; P =.01), and barium (aOR, 0.85; P =.03) levels. Femoral artery plaque associated with cadmium (aOR, 1.72; P <.001) and titanium (aOR, 1.25; P =.01) urine concentrations. Coronary artery plaque associated with exposure to titanium (aOR, 1.16; P =.05).

In the fully adjusted multi-metal model, any plaque risk was increased with exposure to cadmium (aOR, 1.55; 95% CI, 1.12-2.15) and titanium (aOR, 1.19; 95% CI, 1.00-1.44); carotid territory risk with cadmium (aOR, 1.31; 95% CI, 1.00-1.74) and arsenic (aOR, 1.25; 95% CI, 1.04-1.50); femoral territory risk with cadmium (aOR, 1.72; 95% CI, 1.28-2.30) and titanium (aOR, 1.21; 95% CI, 1.01-1.45); and no metals significantly increased risk for coronary territory plaque.

This study was limited by not differentiating between trivalent and hexavalent chromium and there was an insufficient number of women to perform a gender subgroup analysis.

“Our study strengthens the evidence in favor of arsenic and cadmium as proatherogenic risk factors, even at markedly low levels of exposure, and identifies the exposure to titanium and potentially antimony, as novel risk factors for atherosclerosis,” the study authors said. “Additional studies are required to understand the mechanisms involved in the pathogenesis of atherosclerosis associated to metals depending on the vascular territories and metal exposure levels and to evaluate the effects of interventions to prevent and mitigate the potential cardiovascular effects of environmental metals.”


Grau-Perez M, Caballero-Mateos MJ, Domingo-Relloso A, et al. Toxic metals and subclinical atherosclerosis in carotid, femoral, and coronary vascular territories: The Aragon Workers Health Study. Arterioscler Thromb Vasc Biol. Published online December 9, 2021. doi:10.1161/ATVBAHA.121.316358