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.

Keywords: arsenic; cardiovascular disease; dose-response; low level; meta-analysis; systematic review.

Figure 1

Individual study dose-response characteristics for various CVD subtypes or biomarkers. Arsenic concentrations refer to the observed or estimated median arsenic concentrations for the given concentration category. Lines connect the dose-response data for each study and are for illustrative purposes only (CVD: cardiovascular disease; CHD: coronary heart disease).

Figure 2

Pooled log-linear and non-linear relative risks and 95% confidence intervals (CIs) of different CVD endpoints in relation to the estimated drinking water arsenic concentration. Pooled log-linear and non-linear relative risks of CVD endpoints were estimated for drinking water arsenic concentrations with reference to an arsenic concentration of 1 µg/L. Solid lines (red) correspond to pooled relative risks of linear models with their 95% CIs represented as shaded regions (red). Pooled relative risks of non-linear models were represented by long-dash lines (blue) and their 95% CIs were plotted as shaded areas (blue). Log-linear models were estimated with log-transformed estimated drinking water arsenic concentration and non-linear associations were estimated from models with restricted cubic splines of log-transformed water arsenic concentration with knots at the 10th, 50th and 90th percentiles of log-transformed water arsenic (CVD: cardiovascular disease; CHD: coronary heart disease).

Figure 3

Forest plot of individual study and pooled log-linear relative risks (95% confidence intervals (CIs)) of different CVD endpoints, comparing 10 µg/L with 1 µg/L drinking water arsenic concentration. The sizes of squares of the individual study relative risks were weighted by the inverse variance of the log-relative risk within each model (CVD: cardiovascular disease; CHD: coronary heart disease).