Association Between Exposure to Low to Moderate Arsenic Levels and Incident Cardiovascular Disease

Abstract

Background Inorganic arsenic exposure in water and food is a global public health problem. Chronic exposure to high levels of arsenicis consistently associated with increased risk of cardiovascular disease, whereas prospective data on low to moderate chronic arsenic exposure (<100μg/L in drinking water) are lacking. Objective To evaluate the association between chronic low to moderate arsenic exposure and incident cardiovascular disease. Design Prospective cohort study. Setting The Strong Heart Study baseline visit in 1989-1991, with follow-up through 2008. Patients 3,575 American Indian men and women aged 45-74 years living in Arizona, Oklahoma, and North and South Dakota. Measurements The sum of inorganic and methylated arsenic species in urine at baseline was used as a biomarker of chronic arsenic exposure. Participants were followed for incident fatal and non-fatal cardiovascular disease, including coronary heart disease and stroke. Results 1,184 participants developed fatal and non-fatal cardiovascular disease and 439 participants developed fatal cardiovascular disease. Comparing the highest to lowest quartile arsenic concentrations (>15.7 vs. <5.8 μg/g creatinine), the hazard ratios (95% confidence interval) for cardiovascular disease, coronary heart disease, and stroke mortality after adjustment for socio-demographic factors, smoking, body mass index, and lipids were 1.65 (1.20, 2.27; p-trend<0.001), 1.71 (1.19, 2.44; p-trend<0.001) and 3.03 (1.08, 8.50; p-trend=0.061), respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, and stroke were 1.32 (1.09, 1.59; p-trend=0.002), 1.30 (1.04, 1.62; p-trend=0.006), and 1.47 (0.97, 2.21; p-trend=0.032), respectively. These associations varied by study region and were attenuated following further adjustment for diabetes, hypertension, and measures of kidney disease. Limitations Direct measurement of individual arsenic in drinking water was unavailable. Residual confounding and differences in potential confounders across study regions may exist. Conclusions Low to moderate chronic arsenic exposure, as measured in urine, was prospectively associated with cardiovascular disease incidence and mortality.

Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling

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“…Both E max and EC 50 were determined by nonlinear regression analysis using GraphPad Prism version 4.00 (San Diego, California, USA). Potency has been expressed as pD2 = Àlog EC 50 . Data have been expressed as mean ± S.E.…”

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

“…Several recent studies (Chen et al, 2011;Moon et al, 2013) have begun to clarify the potential threshold relationship between low (<100 mg/L) iAs exposure and CVD. The prospective cohort analysis by Chen et al (2011) was chosen by Tsuji et al (2014a) as the critical study for derivation of a RfD (reference dose; i.e., the daily oral dose likely to be without appreciable risk of deleterious effects in a lifetime) for iAs in relation to CVD risk.…”

“…Meanwhile, researchers from the North American Strong Heart Study evaluated the connection between low iAs levels (10-100 mg/L) in drinking water and CVD in 3575 adults living in Native American communities in Arizona, Oklahoma, and North and South Dakota (Moon et al, 2013). Combined inorganic and methylated arsenic species in urine, which are biomarkers of long-term arsenic exposure, were measured in baseline urine samples between 1989 and 1991, and participating patients were followed through 2008.…”

Poultry Consumption and Arsenic Exposure in the U.S. Population

“…Increasing evidence supports that chronic low to moderate iAs exposure results in numerous noncancerous health effects, including cardiovascular, kidney, and respiratory disease; diabetes; and cognitive and reproductive defects (Ahmad et al 2001;Chen et al 2011;Farzan et al 2013Farzan et al , 2015Moon et al 2012Moon et al , 2013Navas-Acien et al 2008;Rahman et al 2009;Tolins et al 2014;Zheng et al 2014). In 2011, the FDA concluded that any animal feed additive that contributed to increased iAs levels in poultry tissues was of concern (FDA 2011).…”