A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh

Environ Health Perspect. 2013 Jul;121(7):832-8. doi: 10.1289/ehp.1205797. Epub 2013 May 10.


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.

Method: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Arsenic / analysis*
  • Arsenicals / urine*
  • Bangladesh / epidemiology
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology*
  • Chromatography, High Pressure Liquid
  • Cohort Studies
  • Drinking Water / analysis*
  • Environmental Exposure*
  • Environmental Monitoring
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Mass Spectrometry
  • Methylation
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Spectrophotometry, Atomic
  • Water Pollutants, Chemical / analysis*
  • Water Pollutants, Chemical / urine*


  • Arsenicals
  • Drinking Water
  • Water Pollutants, Chemical
  • Arsenic