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 > or = 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 (p(trend) = 0.004). Adjusting for blood lead and cadmium levels reduced this odds ratio to 1.37 (p(trend) = 0.13), and further adjusting for estimated glomerular filtration rate and smoking reduced it to 0.89 (p(trend) = 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.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. eguallar@jhsph.edu
Eliseo
E
Guallar
Ellen K
EK
Silbergeld
Ana
A
Navas-Acien
Saurabh
S
Malhotra
Brad C
BC
Astor
A Richey
AR
Sharrett
Brian S
BS
Schwartz
D000328:Adult; D000368:Aged; D002104:Cadmium / Q000097:blood*; D015986:Confounding Factors, Epidemiologic; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006711:Homocystine / Q000097:blood*; D006801:Humans; D007677:Kidney Function Tests; D007854:Lead / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000453:epidemiology; D015995:Prevalence; D012307:Risk Factors; D012907:Smoking / Q000097:blood; D014481:United States / Q000453:epidemiology
D002104:Cadmium; D007854:Lead; D006711:Homocystine