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American Journal of Epidemiology Advance Access originally published online on February 16, 2006
American Journal of Epidemiology 2006 163(8):700-708; doi:10.1093/aje/kwj090
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Original Contribution

Confounding of the Relation between Homocysteine and Peripheral Arterial Disease by Lead, Cadmium, and Renal Function

Eliseo Guallar1,2, Ellen K. Silbergeld3, Ana Navas-Acien3, Saurabh Malhotra1, Brad C. Astor1,2, A. Richey Sharrett1 and Brian S. Schwartz1,3

1 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
2 Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD
3 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

Correspondence to Dr. Eliseo Guallar, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, 2024 East Monument Street, Suite 2-639, Baltimore, MD 21205-2223 (e-mail: eguallar{at}jhsph.edu).

Homocysteine levels are associated with peripheral arterial disease (PAD) in observational studies. Lead and cadmium are risk factors for PAD that affect thiol metabolism, and they may partly explain the association of homocysteine with PAD. To evaluate the roles of lead and cadmium exposure in confounding the association between homocysteine and PAD, the authors performed a cross-sectional study among 4,447 persons aged ≥40 years who participated in the 1999–2002 National Health and Nutrition Examination Survey (NHANES). PAD was defined as an ankle-brachial blood pressure index less than 0.90 in at least one leg. After adjustment for sociodemographic variables, the odds ratio for PAD in the highest quintile of homocysteine compared with the lowest was 1.92 (ptrend = 0.004). Adjusting for blood lead and cadmium levels reduced this odds ratio to 1.37 (ptrend = 0.13), and further adjusting for estimated glomerular filtration rate and smoking reduced it to 0.89 (ptrend = 0.87). Adjustment for other risk factors did not affect this association. In the general population, the association of homocysteine level with PAD can be completely explained by confounding due to smoking, increased blood lead and cadmium levels, and impaired renal function. The association of lead and cadmium with PAD risk deserves further investigation.

cadmium; glomerular filtration rate; homocysteine; lead; peripheral vascular diseases; smoking

Abbreviations: CI, confidence interval; NHANES, National Health and Nutrition Examination Survey; PAD, peripheral arterial disease


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D. S. Sharp
RE: "CONFOUNDING OF THE RELATION BETWEEN HOMOCYSTEINE AND PERIPHERAL ARTERIAL DISEASE BY LEAD, CADMIUM, AND RENAL FUNCTION"
Am. J. Epidemiol., December 1, 2006; 164(11): 1138 - 1138.
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