Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study

Stroke. 2018 Jan;49(1):19-26. doi: 10.1161/STROKEAHA.117.018891. Epub 2017 Dec 6.


Background and purpose: The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States.

Methods: We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species.

Results: The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident.

Conclusions: A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

Keywords: arsenic; environment exposures; minerals; monomethylarsonic acid; risk; stroke; trace elements.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arsenic / toxicity*
  • Arsenicals / urine*
  • Brain Ischemia* / chemically induced
  • Brain Ischemia* / epidemiology
  • Brain Ischemia* / urine
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Stroke* / chemically induced
  • Stroke* / epidemiology
  • Stroke* / urine
  • United States / epidemiology


  • Arsenicals
  • monomethylarsonic acid
  • Arsenic