Arsenic in Drinking Water and Stroke Hospitalizations in Michigan

Abstract

Background and Purpose-Mechanistic and human studies suggest a role for arsenic in ischemic stroke; however, risks from chronic, low-level exposures are uncertain and US studies are lacking. The objective was to investigate the association between low-level arsenic exposure in drinking water and ischemic stroke hospital admissions in Michigan. Methods-Ischemic stroke hospital admissions among those aged Ն45 years were identified (1994 to 2006). Populationweighted average arsenic concentrations were estimated for each Michigan county (nϭ83) and for zip codes in Genesee County (nϭ27) where there is greater variation in arsenic concentrations. US Census data provided age-and sex-specific population counts and other county-and zip code-level variables (race, income), which were adjusted for in multilevel negative binomial regression models of arsenic and stroke admissions. Hospital admissions for duodenal ulcer and hernia, not hypothesized to be associated with arsenic, were also evaluated. Results-Adjusted county-level analyses suggested a relationship between arsenic and ischemic stroke hospital admissions, although similar associations were observed for duodenal ulcer and hernia. In zip code-level analysis, arsenic was associated with an increased risk of stroke admission (relative risk, 1.03; 95% CI, 1.01 to 1.05 per g/L increase in arsenic) after adjustment for confounders, and null or negative associations were found between arsenic and nonvascular outcomes. Conclusions-Findings from this study suggest that exposure to even low levels of arsenic in drinking water may be associated with a higher risk of incident stroke. Given the ecological nature of the analysis, further epidemiological study with individual-level data on arsenic exposure and incident stroke is warranted. (Stroke. 2010;41:2499-2504.)

Mechanisms of action for arsenic in cardiovascular toxicity and implications for risk assessment

“…Part of the difficulty in evaluating relationships to CVD at low exposure levels has been methodological; for instance, in the United States, the heterogeneity of water sources and limited ranges of exposure make it challenging to derive long-term epidemiological conclusions (Moon et al, 2012;Tsuji et al, 2014a). Nonetheless, while some studies of low to moderate iAs exposure are suggestive of a statistically significant relationship between low arsenic exposure and CVD risk (Gong et al, 2012;Lisabeth et al, 2010;Medrano et al, 2010;Rapant et al, 2009;Meliker et al, 2007), conflicting evidence exists (Lewis et al, 1999;Ruiz-Navarro et al, 1998;Zierold et al, 2004). A recent meta-analysis of 31 studies suggests that the evidence does not support a significant relationship between exposure to 50 mg iAs/L water and CVD outcomes (Moon et al, 2012).…”

Cardiovascular effects of arsenic: clinical and epidemiological findings

“…The relationship is particularly evident for peripheral arterial disease ("blackfoot disease" is a form of PAD endemic to areas of Taiwan with extremely high levels of As in drinking water (Tseng 1977)) and coronary heart disease, while the association with stroke is less strong and of borderline significance (Lisabeth et al 2010;Moon et al 2012). The studies globally show a temporal sequence between time of exposure and onset of disease, have yielded consistent results in different countries and populations, show a dose-response relation, and show decreased incidence of disease where reduced exposure has been implemented (Chang et al 2004;Yuan et al 2007).…”

“…However, population data are scarce, while cardiotoxicity of As 2 O 3 as a chemotherapeutic drug is well-known, and is more marked in AfroAmericans, probably due to genetic susceptibility (Patel et al 2006). Specific effects of As on the heart could explain the disproportionate increase in CV events compared to stroke despite the known effect on 7 blood pressure (Zierold et al 2004;Lisabeth et al 2010). Although there appear to be no studies regarding a relationship between heart failure or cardiomyopathy and As, there are hints of a synergistic toxic effect of As and alcohol on the heart (Navas- Acien et al 2006;Bao and Shi 2010b).…”

Arsenic Exposure and Subclinical Endpoints of Cardiovascular Disease

“…Cross-sectional studies from northeastern Taiwan and prospective studies from Bangladesh reported that moderate-to-high levels of arsenic exposure (< 300 μg/L) were associated with CVD prevalence, incidence, and mortality [19-22]. Positive associations of arsenic exposure at low levels (< 100 μg/L) have also been found with CVD mortality in a series of ecological studies from the US and Spain [23-28], and recently, with the risk of overall and subtypes of CVD in a prospective cohort study in the US [29]. Despite the clear epidemiologic links between arsenic exposure and CVD risk, the underlying mechanisms have not been well established.…”