• Björn Fagerberg and Lars Barregard.
• Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
• J. Intern. Med. 2021 Dec 1; 290 (6): 1153-1179.

BackgroundExposure to cadmium (Cd) via food and smoking is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood and urine levels of Cd are established biomarkers of exposure.ObjectivesTo review (1) the smoking-independent associations between Cd exposure and ASCVD, including the possible presence of a nonlinear dose-response relationship with Cd exposure and (2) the causal effects of Cd exposure on different stages of atherosclerosis.MethodsNarrative review.ResultsCd confers increased risk of ASCVD and asymptomatic atherosclerosis in the carotid and coronary arteries above B-Cd >0.5 μg/L or U-Cd >0.5 μg/g creatinine, but it has not been shown below a threshold of these exposure levels. Adjustment for smoking does not exclude the possibility of residual confounding, but several studies in never-smoking cohorts have shown associations between Cd and ASCVD, and experimental studies have demonstrated pro-atherosclerotic effects of Cd. Cd accumulates in arterial walls and atherosclerotic plaques, reaching levels shown to have proatherosclerotic effects. Suggested early effects are increased subendothelial retention of atherogenic lipoproteins, which become oxidized, and endothelial dysfunction and damage with increased permeability for monocytes, which in the intima turn to macrophages and then to foam cells. Later, Cd may contribute to plaque rupture and erosion by endothelial apoptosis and degradation of the fibrous cap. Finally, by having prothrombotic and antifibrinolytic effects, the CVD risk may be further increased.ConclusionsThere is strong evidence that Cd causes ASCVD above a suggested exposure level via mechanisms in early as well as the late stages of atherosclerotic disease.© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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