Association of Urinary Bisphenol A Concentration with Heart Disease: Evidence from NHANES 2003/06

Background Bisphenol A (BPA) is a high production volume chemical widely used in food and drinks packaging. Associations have previously been reported between urinary BPA concentrations and heart disease, diabetes and liver enzymes in adult participants of the National Health and Nutrition Examination Survey (NHANES) 2003/04. We aimed to estimate associations between urinary BPA concentrations and health measures in NHANES 2005/06 and in data pooled across collection years. Methodology and Findings A cross-sectional analysis of NHANES: subjects were n = 1455 (2003/04) and n = 1493 (2005/06) adults aged 18–74 years, representative of the general adult population of the United States. Regression models were adjusted for age, sex, race/ethnicity, education, income, smoking, BMI, waist circumference, and urinary creatinine concentration. Main outcomes were reported diagnoses of heart attack, coronary heart disease, angina and diabetes and serum liver enzyme levels. Urinary BPA concentrations in 2005/06 (geometric mean 1.79 ng/ml, 95% CI: 1.64 to 1.96) were lower than in 2003/04 (2.49 ng/ml, CI: 2.20 to 2.83, difference p-value = 0.00002). Higher BPA concentrations were associated with coronary heart disease in 2005/06 (OR per z-score increase in BPA = 1.33, 95%CI: 1.01 to 1.75, p = 0.043) and in pooled data (OR = 1.42, CI: 1.17 to 1.72, p = 0.001). Associations with diabetes did not reach significance in 2005/06, but pooled estimates remained significant (OR = 1.24, CI: 1.10 to 1.40, p = 0.001). There was no overall association with gamma glutamyl transferase concentrations, but pooled associations with alkaline phosphatase and lactate dehydrogenase remained significant. Conclusions Higher BPA exposure, reflected in higher urinary concentrations of BPA, is consistently associated with reported heart disease in the general adult population of the USA. Studies to clarify the mechanisms of these associations are urgently needed.

[1]  S. R. Mahadik,et al.  Association of adiposity, inflammation and atherosclerosis: the role of adipocytokines and CRP in Asian Indian subjects. , 2008, Metabolic syndrome and related disorders.

[2]  T. Glass,et al.  Association of blood lead and tibia lead with blood pressure and hypertension in a community sample of older adults. , 2006, American journal of epidemiology.

[3]  Shuk-Mei Ho,et al.  Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. , 2007, Reproductive toxicology.

[4]  A. Peters,et al.  Particulate air pollution is associated with an acute phase response in men; results from the MONICA-Augsburg Study. , 2001, European heart journal.

[5]  David E Newby,et al.  Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis , 2005, Circulation.

[6]  Julie E Goodman,et al.  An Updated Weight of the Evidence Evaluation of Reproductive and Developmental Effects of Low Doses of Bisphenol A , 2006, Critical reviews in toxicology.

[7]  M. Toborek,et al.  PCB-induced oxidative stress in endothelial cells: modulation by nutrients. , 2002, International journal of hygiene and environmental health.

[8]  D. Bloch,et al.  A simple method of sample size calculation for linear and logistic regression. , 1998, Statistics in medicine.

[9]  Samuel P. Caudill,et al.  Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population , 2004, Environmental health perspectives.

[10]  Harvey J Clewell,et al.  Evaluation of oral and intravenous route pharmacokinetics, plasma protein binding, and uterine tissue dose metrics of bisphenol A: a physiologically based pharmacokinetic approach. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[11]  S. Swan,et al.  Bisphenol A Data in NHANES Suggest Longer than Expected Half-Life, Substantial Nonfood Exposure, or Both , 2009, Environmental health perspectives.

[12]  Se-Young Oh,et al.  Community level exposure to chemicals and oxidative stress in adult population. , 2009, Toxicology Letters.

[13]  Benoit Nemery,et al.  Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis , 2003, Circulation.

[14]  J. Jeng,et al.  Biological Gradient Between Long-Term Arsenic Exposure and Carotid Atherosclerosis , 2002, Circulation.

[15]  J. Hogg,et al.  Particulate air pollution induces progression of atherosclerosis. , 2002, Journal of the American College of Cardiology.

[16]  I. Jaspers,et al.  Differential activation of AP‐1 in human bladder epithelial cells by inorganic and methylated arsenicals , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  M. E. Hahn,et al.  Induction of cytochrome P4501A1 by aryl hydrocarbon receptor agonists in porcine aorta endothelial cells in culture and cytochrome P4501A1 activity in intact cells. , 1995, Molecular pharmacology.

[18]  D. Melzer,et al.  Association of Bisphenol A With Diabetes and Other Abnormalities—Reply , 2009 .

[19]  G. Franceschini,et al.  Increased plasma and aortic triglycerides in rabbits after acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1984, Toxicology and applied pharmacology.

[20]  F. Grün,et al.  Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis , 2007, Reviews in Endocrine and Metabolic Disorders.

[21]  K. Nakao,et al.  Thyroid hormone action is disrupted by bisphenol A as an antagonist. , 2002, The Journal of clinical endocrinology and metabolism.

[22]  J. Ashby,et al.  Comparison of the modulatory effects of human and rat liver microsomal metabolism on the estrogenicity of bisphenol A: implications for extrapolation to humans. , 2001, The Journal of pharmacology and experimental therapeutics.

[23]  B. Spiegelman,et al.  A Synthetic Antagonist for the Peroxisome Proliferator-activated Receptor γ Inhibits Adipocyte Differentiation* , 2000, The Journal of Biological Chemistry.

[24]  Peter Tontonoz,et al.  Fat and beyond: the diverse biology of PPARgamma. , 2008, Annual review of biochemistry.

[25]  Wolfgang Völkel,et al.  Metabolism and kinetics of bisphenol a in humans at low doses following oral administration. , 2002, Chemical research in toxicology.

[26]  A. Atkinson,et al.  Biochemical and molecular changes at the cellular level in response to exposure to environmental estrogen-like chemicals. , 1997, Journal of toxicology and environmental health.

[27]  Robert B Wallace,et al.  Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. , 2008, JAMA.

[28]  Y. Nakagawa,et al.  Metabolism and cytotoxicity of bisphenol A and other bisphenols in isolated rat hepatocytes , 2000, Archives of Toxicology.

[29]  F. Dominici,et al.  Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994. , 2000, The New England journal of medicine.

[30]  F. Matsumura,et al.  TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) causes reduction in the low density lipoprotein (LDL) receptor activities in the hepatic plasma membrane of the guinea pig and rat. , 1984, Biochemical and biophysical research communications.

[31]  A. Nakajima,et al.  Life style-related diseases of the digestive system: endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome. , 2007, Journal of pharmacological sciences.

[32]  S. Wood.  ON CONFIDENCE INTERVALS FOR GENERALIZED ADDITIVE MODELS BASED ON PENALIZED REGRESSION SPLINES , 2006 .

[33]  Se-Young Oh,et al.  Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women. , 2009, Environmental Research.

[34]  M. Fujishima,et al.  Comparative actions of insulin sensitizers on ion channels in vascular smooth muscle. , 2001, European journal of pharmacology.

[35]  C. Watson,et al.  Xenoestrogens at Picomolar to Nanomolar Concentrations Trigger Membrane Estrogen Receptor-α–Mediated Ca2+ Fluxes and Prolactin Release in GH3/B6 Pituitary Tumor Cells , 2005, Environmental health perspectives.

[36]  Frederick S vom Saal,et al.  Components of plastic: experimental studies in animals and relevance for human health , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[37]  C. Ripoll,et al.  Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. , 2008, International journal of andrology.

[38]  Frederick S vom Saal,et al.  Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. , 2006, Endocrinology.

[39]  L. Cameron,et al.  Polybrominated Biphenyls, Polychlorinated Biphenyls, Body Weight, and Incidence of Adult-Onset Diabetes Mellitus , 2006, Epidemiology.

[40]  Laura N. Vandenberg,et al.  Human exposure to bisphenol A (BPA). , 2007, Reproductive toxicology.

[41]  S Z Cagen,et al.  Three-generation reproductive toxicity study of dietary bisphenol A in CD Sprague-Dawley rats. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[42]  J. Heindel,et al.  Effects of endocrine disruptors on obesity. , 2008, International journal of andrology.

[43]  Samuel P. Caudill,et al.  Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements , 2004, Environmental health perspectives.

[44]  P. Mathur,et al.  Bisphenol A induces reactive oxygen species generation in the liver of male rats. , 2003, Toxicology.

[45]  J Schwartz,et al.  Confounding and Effect Modification in the Short-Term Effects of Ambient Particles on Total Mortality: Results from 29 European Cities within the APHEA2 Project , 2001, Epidemiology.

[46]  J. Sarnat,et al.  Fine particulate air pollution and mortality in 20 U.S. cities. , 2001, The New England journal of medicine.

[47]  S. Chattopadhyay,et al.  Antiandrogenic effects of bisphenol A and nonylphenol on the function of androgen receptor. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[48]  Paloma Alonso-Magdalena,et al.  The Estrogenic Effect of Bisphenol A Disrupts Pancreatic β-Cell Function In Vivo and Induces Insulin Resistance , 2005, Environmental health perspectives.

[49]  Y. Shimohigashi,et al.  Direct Evidence Revealing Structural Elements Essential for the High Binding Ability of Bisphenol A to Human Estrogen-Related Receptor-γ , 2007, Environmental health perspectives.

[50]  Antonia M. Calafat,et al.  Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004 , 2007, Environmental health perspectives.