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Published on: August 11, 2023
Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study
Cari L Tsinovoi1, Pengcheng Xun1, Leslie A McClure1
1From the Departments of Epidemiology and Biostatistics (C.L.T., P.X., K.H.) and Psychiatry (F.W.U.), Indiana University, Bloomington; Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA (L.A.M.); University of Missouri Research Reactor Center, University of Missouri, Columbia (V.M.O.C., J.D.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (J.C.); Department of Epidemiology, Johns Hopkins University, Baltimore, MD (E.G.); Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington (M.C.); and Department of Epidemiology, University of Alabama at Birmingham (V.J.H.).
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.
