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

doi:10.1161/STROKEAHA.117.018891

Randomized Controlled Trial

. 2018 Jan;49(1):19-26.

doi: 10.1161/STROKEAHA.117.018891. Epub 2017 Dec 6.

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

Affiliations

¹ From 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.).
² From 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.). kahe@indiana.edu.

PMID: 29212736
PMCID: PMC5742041
DOI: 10.1161/STROKEAHA.117.018891

Randomized Controlled Trial

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

Cari L Tsinovoi et al. Stroke. 2018 Jan.

. 2018 Jan;49(1):19-26.

doi: 10.1161/STROKEAHA.117.018891. Epub 2017 Dec 6.

Affiliations

¹ From 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.).
² From 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.). kahe@indiana.edu.

PMID: 29212736
PMCID: PMC5742041
DOI: 10.1161/STROKEAHA.117.018891

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 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.

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Conflict of interest statement

Conflicts of Interest

None to declare.

Figures

**Figure 1**
Flow chart featuring the case-cohort sampling scheme of this study.

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References

1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Executive Summary: Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133:447. - PubMed
1. Lanska DJ, Kuller LH. The geography of stroke mortality in the United States and the concept of a stroke belt. Stroke. 1995;26:1145–1149. - PubMed
1. Howard G, Howard VJ, Katholi C, Oli MK, Huston S. Decline in US stroke mortality an analysis of temporal patterns by sex, race, and geographic region. Stroke. 2001;32:2213–2220. - PubMed
1. Howard G, Anderson R, Johnson NJ, Sorlie P, Russell G, Howard VJ. Evaluation of social status as a contributing factor to the stroke belt region of the United States. Stroke. 28:936–940. 997. - PubMed
1. Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM, Muntner P, et al. Life’s Simple 7 and risk of incident stroke the reasons for geographic and racial differences in stroke study. Stroke. 2013;44:1909–1914. - PMC - PubMed

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[1] Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Executive Summary: Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133:447. - PubMed

[2] Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Executive Summary: Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133:447. - PubMed

[3] Lanska DJ, Kuller LH. The geography of stroke mortality in the United States and the concept of a stroke belt. Stroke. 1995;26:1145–1149. - PubMed

[4] Lanska DJ, Kuller LH. The geography of stroke mortality in the United States and the concept of a stroke belt. Stroke. 1995;26:1145–1149. - PubMed

[5] Howard G, Howard VJ, Katholi C, Oli MK, Huston S. Decline in US stroke mortality an analysis of temporal patterns by sex, race, and geographic region. Stroke. 2001;32:2213–2220. - PubMed

[6] Howard G, Howard VJ, Katholi C, Oli MK, Huston S. Decline in US stroke mortality an analysis of temporal patterns by sex, race, and geographic region. Stroke. 2001;32:2213–2220. - PubMed

[7] Howard G, Anderson R, Johnson NJ, Sorlie P, Russell G, Howard VJ. Evaluation of social status as a contributing factor to the stroke belt region of the United States. Stroke. 28:936–940. 997. - PubMed

[8] Howard G, Anderson R, Johnson NJ, Sorlie P, Russell G, Howard VJ. Evaluation of social status as a contributing factor to the stroke belt region of the United States. Stroke. 28:936–940. 997. - PubMed

[9] Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM, Muntner P, et al. Life’s Simple 7 and risk of incident stroke the reasons for geographic and racial differences in stroke study. Stroke. 2013;44:1909–1914. - PMC - PubMed

[10] Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM, Muntner P, et al. Life’s Simple 7 and risk of incident stroke the reasons for geographic and racial differences in stroke study. Stroke. 2013;44:1909–1914. - PMC - PubMed

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

Affiliations

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

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