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

Abstract

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 REasons for Geographic and Racial Differences in Stroke(REGARDS) cohort. A subcohort(n=2,486) 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(iAs) and its metabolites monomethylarsonic acid(MMA) and dimethylarsinic acid(DMA), were measured in a random subset(n=199). Weighted Cox’s proportional hazards models were used to calculate hazard ratios(HRs) and 95% confidence intervals(CIs) of ischemic stroke by arsenic and its species. RESULTS The average follow-up was 6.7 years. While incident ischemic stroke showed no association with total arsenic or total iAs, for each unit higher level of urinary MMA on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased nearly 2-fold(HR=1.98; 95%CI: 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 U.S. general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the etiology of stroke, having important implications for future cerebrovascular research.