Positive Association of Cardiovascular Disease (CVD) with Chronic Exposure to Drinking Water Arsenic (As) at Concentrations below the WHO Provisional Guideline Value: A Systematic Review and Meta-analysis

Abstract

To the best of our knowledge, a dose-response meta-analysis of the relationship between cardiovascular disease (CVD) and arsenic (As) exposure at drinking water As concentrations lower than the WHO provisional guideline value (10 µg/L) has not been published yet. We conducted a systematic review and meta-analyses to estimate the pooled association between the relative risk of each CVD endpoint and low-level As concentration in drinking water both linearly and non-linearly using a random effects dose-response model. In this study, a significant positive association was found between the risks of most CVD outcomes and drinking water As concentration for both linear and non-linear models (p-value for trend < 0.05). Using the preferred linear model, we found significant increased risks of coronary heart disease (CHD) mortality and CVD mortality as well as combined fatal and non-fatal CHD, CVD, carotid atherosclerosis disease and hypertension in those exposed to drinking water with an As concentration of 10 µg/L compared to the referent (drinking water As concentration of 1 µg/L) population. Notwithstanding limitations included, the observed significant increased risks of CVD endpoints arising from As concentrations in drinking water between 1 µg/L and the 10 µg/L suggests further lowering of this guideline value should be considered.

Groundwater Arsenic-Attributable Cardiovascular Disease (CVD) Mortality Risks in India

“…As the basis of this, we generated for the first time a pseudo-contour map of model groundwater arsenic concentrations for the whole of India, based upon the machine learning approach of Podgorski et al [22] and the pseudo-contour approach of Wu et al [20]. Incorporation of CVD dose-response relationships after a recent meta-analysis by Xu et al [24], using the PAF approach rather than an absolute risk vs. dose-response (cf. Mondal et al [31]) has enabled major spatially variable drivers of CVD in India, to a large extent, to be implicitly taken into account in the health-risk modelling.…”

“…Incorporating the dose-response relationships between CVD mortality risk and arsenic in drinking water from a recent meta-analysis by Xu et al [24], the pooled log-linear and non-linear relative risks for each CVD endpoint were calculated for arsenic concentrations of 15 µg/L (mid-point of the 10-20 µg/L category), 35 µg/L (mid-point; 20-50 µg/L), 65 µg/L (mid-point; 50-80 µg/L), and 131 µg/L (a weighted mid-point for the >80 µg/L category), using a drinking water arsenic concentration of 5 µg/L (mid-point for the 0-10 µg/L category) as the reference exposure. The goodness-of-fit of the model was evaluated using deviance tests, coefficient of determination (R 2 and adjusted R 2 ) and Akaike's information criterion (AIC) values.…”

“…The utilized linear and non-linear positive associations between mortality risk of cardiovascular diseases (CVDs) and arsenic concentrations in drinking water with significant overall trends (p < 0.05) were justified based on the recent meta-analysis by Xu et al [24] (Table 1). The relative mortality risks of CVDs of arsenic concentration ranges of 10-20, 20-50, 50-80, and >80 µg/L compared with the reference level of 0-10 µg/L are listed in Table 1.…”

“…Notwithstanding recent spatial distribution models of groundwater arsenic for India, a country-wise and country-specific public health risk model, notably for cardiovascular diseases has not yet been created. The association of CVDs with chronic exposure to arsenic in drinking water have been widely discussed [24][25][26][27][28]. Meta-analysis is a recommended method to quantify the dose-response relationship between CVDs and arsenic exposure, suitably weighting the results of a range of studies [24,29].…”

“…The association of CVDs with chronic exposure to arsenic in drinking water have been widely discussed [24][25][26][27][28]. Meta-analysis is a recommended method to quantify the dose-response relationship between CVDs and arsenic exposure, suitably weighting the results of a range of studies [24,29]. Meanwhile, the populationattributable fraction (PAF) approach is a common method used to quantify potential disease burden reduction in population by eliminating a certain risk factor [30,31].…”