Shankar et al. income, the observed association between BPA levels and PAD may be at least partly explained by residual confounding by low socioeconomic status. Future prospective studies are required to confirm or disprove our findings. A third limitation is that because ABI measures were available only in NHANES 2003–2004, we are not able to examine data from the recent NHANES cycles such as NHANES 2005–2006, where BPA levels may be lower. Fourth, the use of urinary BPA levels measured from a single spot sample is likely to result in some misclassification because of the large variability of BPA. Therefore, to provide the best approach for BPA exposure assessment, expert panels have recommended collection of multiple (rather than single) spot urine samples and study designs that consider important exposure contributors such as the time of the day of sampling (e.g., in relation to food consumption) and the time of last urination (World Health Organization/Food and Agriculture Organization of the United Nations Expert Panel 2011). Finally, urinary BPA levels may not be reflective of the free, unconjugated, circulating BPA in blood, which is considered to be the biologically active form. Future studies examining the health effects of BPA should preferably measure this free, unconjugated part of BPA in serum. Conclusions In a nationally representative sample of U.S. adults, higher BPA levels were positively associated with PAD after adjusting for con- founding factors such as age, sex, smoking, BMI, alcohol intake, diabetes, hypertension, and cholesterol levels. Although our findings must be confirmed in other studies, they pro- vide preliminary evidence that environmental exposure to BPA may contribute to PAD. Ref Rencs Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A. 2006. The estrogenic effect of bisphenol A disrupts pancre- atic b-cell function in vivo and induces insulin resistance. Environ Health Perspect 114:106–112. American Diabetes Association. 2003. Peripheral arterial dis- ease in people with diabetes. Diabetes Care 26:3333–3341. American Diabetes Association. 2011. Diagnosis and classifica- tion of diabetes mellitus. Diabetes Care 34(suppl 1:S62–S69. Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL. 2005. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect 113:391–395. 1300 ovlume 120 | number 9 | September 2012 • Environmental Health Perspectives 116:39–44. Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. 2008. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr. 2003. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42(6):1206–1252. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, et al. 1992. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med Hennig B, Hammock BD, Slim R, Toborek M, Saraswathi V, Robertson LW. 2002. PCB-induced oxidative stress in endothelial cells: modulation by nutrients. Int J Hyg Environ 326:381–386. Health 205:95–102. Halperin JL, et al. 2006. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). Circulation 113:e463–e654; doi: 10.1161/CIRCULATIONAHA.106.174526. Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, et al. 2008. Association of urinary bisphenol A concentration with medical disorders and laboratory abnor- malities in adults. JAMA 300:1303–1310. Hendriksen S, et al. 2006. Using standardized serum creati- nine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:247–254. Marmugi A, Ducheix S, Lasserre F, Polizzi A, Paris A, Priymenko N, et al. 2012. Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumula- tion in adult mouse liver. Hepatology 55:395–407. Masuno H, Iwanami J, Kidani T, Sakayama K, Honda K. 2005. Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway. Toxicol Sci 84:319–327. Matsushima A, Teramoto T, Okada H, Liu X, Tokunaga T, Kakuta Y, et al. 2008. ERRg tethers strongly bisphenol A and 4-a-cumylphenol in an induced-fit manner. Biochem Biophys Res Commun 373:408–413. Melzer D, Rice NE, Lewis C, Henley WE, Galloway TS. 2010. Association of urinary bisphenol A concentration with heart disease: evidence from NHANES 2003/06. PLoS One 5:e8673; doi:10.1371/journal.pone.0008673 [Online 13 January 2010]. Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, A as an antagonist. J Clin Endocrinol Metab 87:5185–5190. Murabito JM, Evans JC, Larson MG, Nieto K, Levy D, Wilson PW. 2003. The ankle–brachial index in the elderly and risk of stroke, coronary disease, and death: the Framingham Study. Arch Intern Med 163:1939–1942. National Kidney Foundation. 2002. K/DOQI Clinical practice guidelines for chronic kidney disease: evaluation, classifi- cation, and stratification. Am J Kidney Dis 39:S1–S266. (LEXAB_C). Available: http://www.cdc.gov/nchs/nhanes/ nhanes2003-2004/LEXAB_C.htm [accessed 4 May 2011]. NCHS (National Center for Health Statistics). 2010b. 2003–2004 National Health and Nutrition Examination Survey: Survey Operations Manuals, Brochures, Consent Documents. Available: http://www.cdc.gov/nchs/nhanes/nhanes2003- 2004/current_nhanes_03_04.htm [accessed 22 April 2011]. NCHS (National Center for Health Statistics). 2010c. Laboratory Procedure Manual for Serum Creatinine. Available: http:// www.cdc.gov/nchs/data/nhanes/nhanes_03_04/l40_c_met_ creatinine.pdf [accessed 26 September 2011]. NCHS (National Center for Health Statistics). 2010d. NHANES 2003–2004 Data Release: January 2006. General Information about the NHANES 2003–2004 Laboratory Methodology and Public Data Files. Available: http://www.cdc.gov/nchs/data/ nhanes/nhanes_03_04/lab_c_generaldoc.pdf [accessed 88:114–126. Biol 110:95–103. Newbold RR, Padilla-Banks E, Jefferson WN. 2009. Environmental estrogens and obesity. Mol Cell Endocrinol 304:84–89. Newman AB, Siscovick DS, Manolio TA, Polak J, Fried LP, Borhani NO, et al. for the Cardiovascular Heart Study (CHS) Collaborative Research Group. 1993. Ankle–arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Circulation 88:837–845. Ooe H, Taira T, Iguchi-Ariga SM, Ariga H. 2005. Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A–induced cell injury by DJ-1. Toxicol Sci Phrakonkham P, Viengchareun S, Belloir C, Lombes M, Artur Y, Canivenc-Lavier MC. 2008. Dietary xenoestrogens dif- ferentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis. J Steroid Biochem Mol Fuentes E, Nadal A. 2008. Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. Int J Androl 31:194–200. Rubin BS, Soto AM. 2009. Bisphenol A: Perinatal exposure and body weight. Mol Cell Endocrinol 304:55–62. Selvin E, Erlinger TP. 2004. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation 110:738–743. Selvin E, Manzi J, Stevens LA, Van LF, Lacher DA, Levey AS, et al. 2007. Calibration of serum creatinine in the National Health and Nutrition Examination Surveys (NHANES) 1988–1994, 1999–2004. Am J Kidney Dis 50:918–926. Stegeman JJ, Hahn ME, Weisbrod R, Woodin BR, Joy JS, Najibi S, et al. 1995. Induction of cytochrome P4501A1 by aryl hydrocarbon receptor agonists in porcine aorta endothelial cells in culture and cytochrome P4501A1 activity in intact cells. Mol Pharmacol 47:296–306. Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM. 2009. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 30:75–95. of the United Nations Expert Panel. 2011. Toxicological and Health Aspects of Bisphenol A. Available at: http:// whqlibdoc.who.int/publications/2011/97892141564274_eng. pdf [accessed 26 September 2011]. Wright HM, Clish CB, Mikami T, Hauser S, Yanagi K, Hiramatsu R, et al. 2000. A synthetic antagonist for the peroxisome proliferator–activated receptor g inhibits adipocyte differen- tiation. J Biol Chem 275:1873–1877. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, 22 April 2011]. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Ropero AB, Alonso-Magdalena P, Garcia-Garcia E, Ripoll C, et al. 2002. Thyroid hormone action is disrupted by bisphenol World Health Organization/Food and Agriculture Organization NCHS (National Center for Health Statistics). 2010a. 2003–2004 Ye X, Kuklenyik Z, Needham LL, Calafat AM. 2005. Automated National Health and Nutrition Examination Survey: 2003–2004 Data Documentation, Codebook, and Frequencies—Lower Extremity Disease–Ankle Brachial Blood Pressure Index on-line column-switching HPLC-MS/MS method with peak focusing for the determination of nine environmental phenols in urine. Anal Chem 77:5407–5413.