Background— Lead and cadmium exposure may promote atherosclerosis, although the cardiovascular effects of chronic low-dose exposure are largely unknown. The objective of the present study was to evaluate the association between blood levels of lead and cadmium and peripheral arterial disease.

Methods and Results— We analyzed data from 2125 participants who were ≥40 years of age in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES). Peripheral arterial disease was defined as an ankle brachial index <0.9 in at least 1 leg. Lead and cadmium levels were measured by atomic absorption spectrometry. After adjustment for demographic and cardiovascular risk factors, the ORs of peripheral arterial disease comparing quartiles 2 to 4 of lead with the lowest quartile were 1.63 (95% CI, 0.51 to 5.15), 1.92 (95% CI, 0.62 to 9.47), and 2.88 (95% CI, 0.87 to 9.47), respectively (P for trend=0.02). The corresponding ORs for cadmium were 1.07 (95% CI, 0.44 to 2.60), 1.30 (95% CI, 0.69 to 2.44), and 2.82 (95% CI, 1.36 to 5.85), respectively (P for trend=0.01). The OR of peripheral arterial disease for current smokers compared with never smokers was 4.13. Adjustment for lead reduced this OR to 3.38, and adjustment for cadmium reduced it to 1.84.

Conclusions— Blood lead and cadmium, at levels well below current safety standards, were associated with an increased prevalence of peripheral arterial disease in the general US population. Cadmium may partially mediate the effect of smoking on peripheral arterial disease.