Exposure to cadmium (Cd) via food and smoking is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood and urine levels of Cd are established biomarkers of exposure. Our aim was to review: 1) the smoking-independent associations between Cd exposure and ASCVD, including the possible presence of a non-linear dose-response relationship with Cd exposure; and 2) the causal effects of Cd exposure on different stages of atherosclerosis. The results indicate that Cd 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 mechanisms are increased subendothelial retention of atherogenic lipoproteins, which become oxidized; 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. In summary, there is strong evidence that Cd causes ASCVD above a suggested exposure level via mechanisms in early, as well as late stages of atherosclerotic disease. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.