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Lead, Cadmium, Smoking, and Increased Risk of Peripheral Arterial Disease

Ana Navas-Acien, MD, MPH; Elizabeth Selvin, MPH; A. Richey Sharrett, MD, DrPH;
Emma Calderon-Aranda, PhD, MD; Ellen Silbergeld, PhD; Eliseo Guallar, MD, DrPH

Background—Lead and cadmium exposure may promote atherosclerosis, although the cardiovascular effects of chroniclow-dose exposure are largely unknown. The objective of the present study was to evaluate the association betweenblood 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 NationalHealth 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 leadwith 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 trend0.02). 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 trend0.01). The OR of peripheral arterial diseasefor 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. (Circulation. 2004;109:3196-3201.)

Key Words: cadmium lead peripheral vascular diseases smoking