title: A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh.
abstract: BACKGROUND
  Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk.
  
  
  OBJECTIVE
  We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk.
  
  
  METHODS
  We conducted a case-cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS).
  
  
  RESULTS
  The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity--indicated by higher urinary MMA% or lower urinary DMA%--with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking.
  
  
  CONCLUSIONS
  Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk.
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York 10016, USA. yu.chen@nyumc.org
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Fen
authors.initials: F
authors.lastname: Wu
authors.forename: Mengling
authors.initials: M
authors.lastname: Liu
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.forename: Mahbub
authors.initials: M
authors.lastname: Eunus
authors.forename: Alauddin
authors.initials: A
authors.lastname: Ahmed
authors.forename: Maria
authors.initials: M
authors.lastname: Argos
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rakibuz-Zaman
authors.forename: Rabiul
authors.initials: R
authors.lastname: Hasan
authors.forename: Golam
authors.initials: G
authors.lastname: Sarwar
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.forename: Joseph
authors.initials: J
authors.lastname: Graziano
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
mesh_terms: D000328:Adult; D001151:Arsenic / Q000032:analysis*; D001152:Arsenicals / Q000652:urine*; D001459:Bangladesh / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D060766:Drinking Water / Q000032:analysis*; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013054:Spectrophotometry, Atomic; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000652:urine*
chemical_list: D001152:Arsenicals; D060766:Drinking Water; D014874:Water Pollutants, Chemical; D001151:Arsenic