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

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.

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As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 04-13-2009
Authors: Eliseo Guallar1,2, Ellen K. Silbergeld3, Ana Navas-Acien3, Saurabh Malhotra1, Brad C. Astor1,2, A. Richey Sharrett1 and Brian S. Schwartz1,3
Source: American Journal of Epidemiology Advance Access originally published online on February 16, 2006