American Journal of Epidemiology Advance Access published online on February 16, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj090
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1 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD
* To whom correspondence should be addressed. 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
Received October 4, 2005
Accepted November 11, 2005
ORIGINAL CONTRIBUTIONS
Confounding of the Relation between Homocysteine and Peripheral Arterial Disease by Lead, Cadmium, and Renal Function
Eliseo Guallar 1 *,
Ellen K. Silbergeld 2,
Ana Navas-Acien 2,
Saurabh Malhotra 3,
Brad C. Astor 1,
A. Richey Sharrett 3,
and
Brian S. Schwartz 4
2 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
3 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
4 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
Eliseo Guallar, E-mail: eguallar{at}jhsph.edu
Abstract 
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.
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