Exposure to Inorganic Arsenic in Drinking Water and CHD
Background Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associations have been inconclusive in populations with lower levels (< 100 μg/L) of inorganic arsenic exposure.
Objectives We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD.
Methods This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD.
Results We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 μg/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 μg/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20–30 μg/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30–45 μg/L; and HR = 3, 95% CI: 1.1, 9.1 for 45–88 μg/L).
Conclusions Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population.
Nonoccupational exposure to inorganic arsenic occurs mainly through drinking contaminated water [U.S. Environmental Protection Agency (EPA) 1988]. In recent decades, research has identified a relationship between exposure to high concentrations of inorganic arsenic in drinking water and the risk of coronary heart disease (CHD); however, the risk at lower levels is ambiguous. Studies from Asia, where water concentrations of inorganic arsenic can be > 1,000 μg/L, have reported inorganic arsenic in drinking water to be associated with ischemic heart disease and carotid atherosclerosis (Chen CJ et al. 1996; Tseng et al. 2003; Wang et al. 2002), hypertension (Chen CJ et al. 1995, 2007; Chen Y et al. 2006a; Rahman et al. 1999), and intermediate outcomes associated with CHD including carotid artery intimal–medial thickness (Chen Y et al. 2006b) and ECG changes (Wang et al. 2010).
An association of cardiovascular risk with low-level arsenic exposure in drinking water (< 100 μg/L) has been suggested by recent studies (Chen Y et al. 2011; Moon et al. 2013). In a study by Chen Y et al. (2011), results suggested a higher cardiovascular mortality rate with exposure to drinking water arsenic concentrations > 12 μg/L, and an increasing trend in hazard ratios (HRs) with increasing arsenic exposure (log rank trend test = 0.0019) while controlling for known CHD risk factors. Positive associations were reported by other studies with similar exposure levels (< 100 μg/L) (Medrano et al. 2010; Sohel et al. 2009). These findings suggest that increased risk for cardiovascular disease occurs at levels similar to concentrations found in drinking water in areas of the United States.
In the United States, where arsenic concentrations are generally < 100 μg/L, ecologic studies (Engel and Smith 1994; Engel et al. 1994; Lewis et al. 1999; Meliker et al. 2007; Zierold et al. 2004) and review articles (Navas-Acien et al. 2005; Wang et al. 2007) have suggested a possible association of drinking-water arsenic with CHD, hypertension, and carotid intimal thickness. However, it has been only recently that chronic exposure to low to moderate levels inorganic arsenic in drinking water has been investigated as an independent risk factor for cardiovascular diseases in a prospective study. Moon et al. (2013) reported an association between urinary arsenic concentrations and coronary heart disease [HR = 1.16; 95% confidence interval (CI): 1.03, 1.30 per 9.9 μg/g adjusted for CHD risk factors] in U.S. American Indian communities. These findings in the Strong Heart Study (Moon et al. 2013) were the first to prospectively assess low- to moderate-level inorganic arsenic exposure in urine with cardiovascular disease at a community level; however, the study was limited in assessing exposure at the individual level. Future research that prospectively follows a cohort representative of U.S. communities with individual-level exposure assessment is necessary to further substantiate the association between inorganic arsenic exposure in drinking water and cardiovascular disease and elucidate the dose–response curve.
Abstract and Introduction
Abstract
Background Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associations have been inconclusive in populations with lower levels (< 100 μg/L) of inorganic arsenic exposure.
Objectives We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD.
Methods This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD.
Results We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 μg/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 μg/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20–30 μg/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30–45 μg/L; and HR = 3, 95% CI: 1.1, 9.1 for 45–88 μg/L).
Conclusions Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population.
Introduction
Nonoccupational exposure to inorganic arsenic occurs mainly through drinking contaminated water [U.S. Environmental Protection Agency (EPA) 1988]. In recent decades, research has identified a relationship between exposure to high concentrations of inorganic arsenic in drinking water and the risk of coronary heart disease (CHD); however, the risk at lower levels is ambiguous. Studies from Asia, where water concentrations of inorganic arsenic can be > 1,000 μg/L, have reported inorganic arsenic in drinking water to be associated with ischemic heart disease and carotid atherosclerosis (Chen CJ et al. 1996; Tseng et al. 2003; Wang et al. 2002), hypertension (Chen CJ et al. 1995, 2007; Chen Y et al. 2006a; Rahman et al. 1999), and intermediate outcomes associated with CHD including carotid artery intimal–medial thickness (Chen Y et al. 2006b) and ECG changes (Wang et al. 2010).
An association of cardiovascular risk with low-level arsenic exposure in drinking water (< 100 μg/L) has been suggested by recent studies (Chen Y et al. 2011; Moon et al. 2013). In a study by Chen Y et al. (2011), results suggested a higher cardiovascular mortality rate with exposure to drinking water arsenic concentrations > 12 μg/L, and an increasing trend in hazard ratios (HRs) with increasing arsenic exposure (log rank trend test = 0.0019) while controlling for known CHD risk factors. Positive associations were reported by other studies with similar exposure levels (< 100 μg/L) (Medrano et al. 2010; Sohel et al. 2009). These findings suggest that increased risk for cardiovascular disease occurs at levels similar to concentrations found in drinking water in areas of the United States.
In the United States, where arsenic concentrations are generally < 100 μg/L, ecologic studies (Engel and Smith 1994; Engel et al. 1994; Lewis et al. 1999; Meliker et al. 2007; Zierold et al. 2004) and review articles (Navas-Acien et al. 2005; Wang et al. 2007) have suggested a possible association of drinking-water arsenic with CHD, hypertension, and carotid intimal thickness. However, it has been only recently that chronic exposure to low to moderate levels inorganic arsenic in drinking water has been investigated as an independent risk factor for cardiovascular diseases in a prospective study. Moon et al. (2013) reported an association between urinary arsenic concentrations and coronary heart disease [HR = 1.16; 95% confidence interval (CI): 1.03, 1.30 per 9.9 μg/g adjusted for CHD risk factors] in U.S. American Indian communities. These findings in the Strong Heart Study (Moon et al. 2013) were the first to prospectively assess low- to moderate-level inorganic arsenic exposure in urine with cardiovascular disease at a community level; however, the study was limited in assessing exposure at the individual level. Future research that prospectively follows a cohort representative of U.S. communities with individual-level exposure assessment is necessary to further substantiate the association between inorganic arsenic exposure in drinking water and cardiovascular disease and elucidate the dose–response curve.