Abstract and Introduction
Abstract
Background: Bisphenol A (BPA) is a common chemical used in the manufacture of polycarbonate plastics and epoxy resins, and > 93% of U.S. adults have detectable levels of urinary BPA. Recent animal studies have suggested that BPA exposure may have a role in several mechanisms involved in the development of cardiovascular disease (CVD), including weight gain, insulin resistance, thyroid dysfunction, endothelial dysfunction, and oxidative stress. However, few human studies have examined the association between markers of BPA exposure and CVD. Peripheral arterial disease (PAD) is a subclinical measure of atherosclerotic vascular disease and a strong independent risk factor for CVD and mortality.
Objective: We examined the association between urinary BPA levels and PAD in a nationally representative sample of U.S. adults.
Methods: We analyzed data from 745 participants in the National Health and Nutritional Examination Survey 2003–2004. We estimated associations between urinary BPA levels (in tertiles) and PAD (ankle–brachial index < 0.9, n = 63) using logistic regression models adjusted for potential confounders (age, sex, race/ethnicity, education, smoking, body mass index, diabetes mellitus, hypertension, urinary creatinine, estimated glomerular filtration rate, and serum cholesterol levels).
Results: We observed a significant, positive association between increasing levels of urinary BPA and PAD before and after adjusting for confounders. The multivariable-adjusted odds ratio for PAD associated with the highest versus lowest tertile of urinary BPA was 2.69 (95% confidence interval: 1.02, 7.09; p-trend = 0.01).
Conclusions: Urinary BPA levels were significantly associated with PAD, independent of traditional CVD risk factors.
Introduction
Bisphenol A (BPA) is a chemical produced in very high volume, with > 2 million metric tons produced worldwide in 2003 (Vandenberg et al. 2009) and used extensively in the manufacture of epoxy resins, polycarbonate plastics, and food and beverage containers (Vandenberg et al. 2009). Consequently, it is one of the most common environmental chemical exposures in humans (Calafat et al. 2005). Data from the nationally representative National Health and Nutrition Examination Survey (NHANES) suggest that detectable levels of BPA are present in the urine of a majority of U.S. adults (Calafat et al. 2005, 2008).
BPA is considered to be an endocrine-disrupting chemical, and it has been shown to have estrogenic and thyroid hormone–disrupting effects in experimental studies (Moriyama et al. 2002; Vandenberg et al. 2009). Recent evidence, especially from animal studies, suggests that BPA exposure may be related to insulin resistance and have a role in weight gain and obesity and the subsequent development of diabetes mellitus (Newbold et al. 2009; Rubin and Soto 2009). Two recent human studies reported that higher urinary BPA levels were associated with self-reported cardiovascular disease (CVD) (Lang et al. 2008; Melzer et al. 2010). However, studies examining the relation between BPA exposure and more objective measures of CVD are needed to support this putative association.
Peripheral arterial disease (PAD) is a subclinical measure of atherosclerotic vascular disease (Newman et al. 1993) that is an independent predictor of subsequent incident CVD (Murabito et al. 2003; Newman et al. 1993). Criqui et al. (1992) reported that among persons initially free of CVD, an ankle–brachial index (ABI) of < 0.9 was associated with a hazard ratio of 6.6 for future risk of death from coronary heart disease even after adjusting for cardiovascular risk factors including age, sex, body mass index (BMI), smoking, and high cholesterol levels. Published guidelines (American Diabetes Association 2003; Hirsch et al. 2006) exist for defining PAD based on the ABI, which can be measured even in large population-based studies (Selvin and Erlinger 2004). In this context, we examined the independent association between urinary BPA levels and PAD among participants in the 2003–2004 NHANES, a representative, multiethnic sample of U.S. adults.