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Low-Level Cadmium Exposure and Atherosclerosis

  • Metals and Health (R Fry, Section Editor)
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Abstract

Purpose of Review

Cadmium has been recognized as a potential risk factor for cardiovascular disease (CVD). We present a review of cadmium toxicity, its effect on cellular activities, and a summary of reported association between environmental cadmium exposure and CVD. We also discuss the possible therapeutic benefit of cadmium chelation.

Recent Findings

Experimental data suggest that cadmium affects several signaling pathways which may lead to endothelial dysfunction and vascular tissue damage, promoting atherosclerosis. This is further supported by epidemiological studies that have shown an association of even low-level cadmium exposure with an increased risk of clinical cardiovascular events. The Trial to Assess Chelation Therapy (TACT) provided inferential evidence for the cardiovascular benefit of treating toxic metal burden. However, at the present time, there is no direct evidence, but suggestive findings from clinical trials indicating that removal of cadmium from body stores may be associated with improved cardiovascular outcomes.

Summary

An evolving body of evidence supports environmental cadmium exposure as a pro-atherosclerosis risk factor in CVD; however, the mechanisms for the proatherogenic effect of cadmium are still not completely understood. Further studies in translational toxicology are needed to fill the knowledge gaps regarding the molecular mechanisms of cadmium toxicity and the promotion of atherosclerosis.

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Abbreviations

Cd:

Cadmium

CVD:

Cardiovascular disease

TACT:

Trial to assess chelation therapy

MI:

Myocardial infarction

Ca2+ :

Calcium

SMCs:

Smooth muscle cells

VDCC:

Voltage-dependent calcium channels

IP3:

Inositol triphosphate

PKC:

Protein kinase C

CAMK:

Calmodulin dependent enzyme

MAPK:

Mitogen-activated protein kinase

NO:

Nitric oxide

PON1:

Paraoxonase 1

NF-kB:

Nuclear factor kappa B

NHANES:

National Health and Nutrition Examination Survey

PAD:

Peripheral arterial disease

RNA:

Ribonucleic acid

EDTA:

Edetate disodium

BAL:

Dimercapral

DMPS:

Dimercaptopropanesulfonic acid

DMSA:

Dimercaptosuccinic acid

LDL:

Low-density lipoprotein

OR:

Odds ratio

HR:

Hazard ratio

CI:

Confidence interval

NNT:

Number needed to treat

CLI:

Critical limb ischemia

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Authors and Affiliations

  1. Columbia University Division of Cardiology, Mount Sinai Medical Center, 4300 Alton Road, Suite # 2070A, Miami Beach, FL, 33140, USA

    Denisse Diaz, Gervasio A. Lamas & Ivan A. Arenas

  2. Department of Medicine, Mount Sinai Medical Center, Miami Beach, FL, USA

    Francisco Ujueta, Gisell Mansur & Gervasio A. Lamas

  3. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA

    Ana Navas-Acien

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  1. Denisse Diaz
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  2. Francisco Ujueta
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Diaz, D., Ujueta, F., Mansur, G. et al. Low-Level Cadmium Exposure and Atherosclerosis. Curr Envir Health Rpt 8, 42–53 (2021). https://doi.org/10.1007/s40572-021-00304-w

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