The risk of all-cause mortality and chronic-disease mortality increased with increasing arsenic exposure. Moreover, the data indicate that there is a trend in risk within the arsenic range to which this population was exposed. With repeated measurements of total arsenic concentrations in urine from all cohort members, long-term exposure to arsenic (captured by use of the baseline ascertainment of exposure) was a more important predictor of mortality than were subsequent short-term changes of exposure (derived from the 2-year and 4-year follow-up assessments of total arsenic concentrations in urine). Based on the risk estimates, an estimated 21·4% of all deaths and 23·5% of deaths associated with chronic disease in this population could be attributed to arsenic exposure (>10 μg/L) in drinking water.
Whereas in previous studies, associations were shown between arsenic exposure and cause-specific mortality,4,5,7,9,11,16,18,27,28
in this population-based study we prospectively investigated the association between arsenic exposure in drinking water and all-cause mortality in a Bangladeshi population. Ecological measurements of arsenic exposure and other potential confounders were used in the analyses of other studies, making them more susceptible to measurement error in exposure assessment and ecological bias. For example, Wu and colleagues9
showed significant dose-response patterns in mortality rates associated with cancers of the lung, skin, bladder, and kidney at the village level, but stated that their findings might not apply at the individual level. One of the main strengths of this analysis is that associations between arsenic exposure and mortality were measured at the individual level, reducing to a minimum the consequences of confounding and exposure measurement error, and strengthening causal inference at the individual level. Furthermore, previous studies were largely done in populations exposed to high concentrations of arsenic. A wide range of concentrations of arsenic exposure was present in our study area (arsenic concentrations in well water were 0·1–864·0 μg/L); therefore, we had the opportunity to evaluate arsenic-associated mortality rate at the low exposure range for which there was evidence of increased mortality risk.
With repeated measurements of total arsenic concentration in urine with time, we noted that once chronically exposed, decreasing exposure for a short amount of time did not reduce an individual’s risk of mortality. However, we will continue to assess the modification of risk as the cohort is followed up for longer than in this study. In other studies, mortality rate attributed to cancers and heart disease did not begin to decline until about two decades after prevention of exposure to high concentrations of arsenic in well water.28,29
Therefore, evidence from these studies and our data suggest that other health strategies for prevention and promotion with remediation for arsenic-exposed populations are important and should be considered.
To assess potential confounding by prevalent medical disorders, deaths that occurred in the first 2 years after enrolment into the cohort were excluded from analyses. Associations between arsenic concentrations in well water and mortality did not change much (after exclusions), suggesting that medical disorders prevalent at baseline presented minimum confounding effects. A possible limitation of this analysis was that comorbid disorders were not included in the model of total arsenic concentration in urine since some of them could affect total arsenic concentrations in urine and mortality rate; however, since the effect estimates noted with total arsenic concentration in urine were similar to the results noted with arsenic concentrations in well water, we do not judge this limitation to be a major source of bias in this analysis. Additionally, the association between arsenic exposure and mortality associated with chronic disease (excluding deaths unlikely to be related to arsenic exposure) was similar to results of the associations noted for all-cause mortality. Moreover, analyses of mortality associated with chronic disease produced more apparent trends in the low-to-moderate arsenic exposure ranges compared with all-cause mortality.
We used several measures of arsenic exposure in this analysis derived at the individual level from water-based and urine-based ascertainments of exposure. The associations noted with each of the assessments of exposure were similar, suggesting that measurement error or misclassification of chronic arsenic exposure was kept to a minimum in this study. The slightly attenuated effect estimates for the associations between daily arsenic dose and mortality rate compared with arsenic in well water might be explained by measurement error in the assessment of self-reported daily water consumption.
The major strengths of this study were the prospective design, large size of the study cohort, wide range of arsenic exposures, several measurements of baseline arsenic exposure, the repeated prospective assessment of total arsenic concentration in urine, and nearly complete follow-up for vital status. The results of this study have important public health implications for arsenic in drinking water. Roughly 24% of the people in the cohort had arsenic concentrations in well water less than 10 μg/L, and 45% had less than 50 μg/L, which makes the exposure levels similar to other populations that have low-level arsenic exposure.
This study also had limitations. Whereas total arsenic concentration in urine for the cohort measured by use of graphite furnace atomic absorption is the most cost-efficient and feasible method for measurement of arsenic concentrations in a large-scale cohort, it does not allow for the specific estimation of the fractions of arsenobetaine or arsenocholine. Detailed speciation studies of random subsets from our study cohort have shown a very small percentage (3%) of total arsenic concentration in urine to be arsenobetaine and arsenocholine.30
Therefore, we do not believe that our results would differ much with the exclusion of this fraction.
We noted significant associations between arsenic exposure through drinking water and mortality rate, emphasising the public health challenge for millions of Bangladeshis due to this environmental exposure. Although initiatives to reduce exposure to arsenic in drinking water are in progress, investigation into solutions to mitigate the resulting health effects of this catastrophe deserve urgent attention and resources. Future research with prospectively gathered data for changes at the individual level in arsenic exposure will strengthen our understanding of the effect that changes in exposure have on long-term mortality risk.