In a representative sample of U.S. adults who participated in NHANES 2003–2008, we found no association between urine concentrations of total arsenic or total arsenic minus arsenobetaine with the prevalence of hypertension or with systolic and diastolic blood pressure levels. For urine DMA, while no association was found with systolic or diastolic blood pressure, the findings for hypertension could be consistent with no association or with a small positive association, especially in certain subgroups (such as participants with BMI ≥ 30 kg/m2 or in never-smokers). Subgroup findings, however, need to be considered cautiously as we had no a priori hypothesis and these analyses were exploratory.
Most studies investigating the association between arsenic exposure and hypertension endpoints have been conducted at much higher levels of exposure than those in the general U.S. population.7,9,11,27–29
Most of these studies assessed arsenic exposure based on measures of arsenic in drinking water. Chronic exposure to high levels of inorganic arsenic in drinking water (median levels ranging from <500 to >1000 μg/L) have been associated with the prevalence of hypertension in Taiwan and Bangladesh.9,10
In a cross-sectional study of 898 residents in Southwestern Taiwan, the multivariate-adjusted OR for hypertension comparing participants with cumulative arsenic exposure >18.5 mg/L-years to <0.1 mg/L-years was 2.9 (1.1 to 7.3).9
In a cross-sectional study of 1481 residents in Bangladesh, the OR for hypertension comparing participants with cumulative arsenic exposure >10.0 mg/L-years to unexposed participants was 3.0 (95% CI = 1.5 to 5.8) after adjustment for age, sex and BMI.10
In contrast, another cross-sectional study conducted in Bangladesh (n = 10,910) found that time-weighted well arsenic concentration was not associated with hypertension,11
although increasing arsenic concentrations in drinking water were associated with systolic hypertension (systolic ≥ 140mmHg) and with high pulse pressure (≥ 55mmHg), especially among participants with low vitamin B6, B12 or folate levels.11
In our study, the results were similar after further adjustment for serum folate and vitamin B12 and in analyses stratified by serum folate and vitamin B12 levels, although folate and vitamin B levels are substantially higher in the US than in Bangladesh.
Few studies have addressed the association of low or moderate exposure to inorganic arsenic with hypertension.12,30,31
In a cross-sectional study in Wisconsin, the age, sex and BMI adjusted OR for self-reported hypertension comparing residents with arsenic levels in well water between 2 and 10 μg/L and >10 μg/L to <2 μg/L were 1.2 (95% CI = 0.8 to 1.6) and 1.7 (1.1 to 2.5), respectively.12
In 432 participants exposed to relatively low arsenic levels in drinking water in Central Taiwan, hair arsenic levels were associated with the prevalence of hypertension.31
In an occupational study of 59 workers in Denmark, mean systolic and diastolic blood pressure levels were higher in arsenic-exposed workers (median total urine arsenic = 14.8 μg/g of creatinine) compared with unexposed workers (7.9 μg/g of creatinine).8
This study was small and did not adjust for hypertension risk factors. The concentrations of total urine arsenic, although not high compared with levels in populations exposed to arsenic in drinking water in Taiwan and Bangladesh, were higher than in NHANES participants.
No previous epidemiologic study has evaluated the relationship of urine arsenic with blood pressure endpoints, even though total urine arsenic and DMA are well-established biomarkers of arsenic exposure.3,32,33
We used total urine arsenic, total arsenic minus arsenobetaine, and DMA in models with and without adjustment for urine arsenobetaine, all with similar findings. Adjustment for arsenobetaine, a biomarker of seafood intake, was important to remove the contribution of organic arsenicals in seafood, including arsenosugars and arsenolipids (forms that are difficult to measure in epidemiologic studies but that co-occur with arsenobetaine in seafood), to total arsenic, total arsenic minus arsenobetaine, and DMA.25,34
To further confirm that the lack of association between total arsenic, total arsenic minus arsenobetaine, and DMA with hypertension was not related to organic arsenicals, we conducted sensitivity analyses in participants with undetectable arsenobetaine. In this subsample, total urine arsenic and urine DMA are likely to reflect exposure to inorganic arsenic from water and food other than seafood.25
The results were similar and consistent with no association between exposure to inorganic arsenic and hypertension endpoints at low to moderate levels of exposure.
Strengths and limitations
This study, characterized by rigorous quality control measures, was conducted in a representative sample of the U.S. population. To date, this is the largest study of arsenic exposure and hypertension endpoints at low to moderate levels, and among the few using urine arsenic biomarkers. The cross-sectional design does not allow for the establishment of temporality between arsenic exposure and changes in blood pressure levels. In addition, we were limited by the use of one single spot urine sample to measure arsenic. Inorganic arsenic has a relatively short half-life (approximately 2–38 days for the different inorganic arsenic species and its methylated metabolites) and arsenic concentrations measured in urine samples may not reflect chronic arsenic exposure. In the absence of interventions, however, arsenic concentrations in drinking water (a major source for the general population) are relatively stable over time.35–37
Urine arsenic concentrations in the U.S. have been shown to remain relatively constant over many years.38
In Taiwan, a single urine arsenic measure was also well correlated with cumulative arsenic exposure in drinking water.29
We could not evaluate the role of geographic region in arsenic exposure levels. Certain regions of the US, particularly rural areas in the Western, Midwestern and Northeastern states, experience substantial arsenic exposure due to elevated concentrations of inorganic arsenic in groundwater. While the study sample is representative of the U.S. population, the findings cannot be applied to US populations living in areas with high arsenic in drinking water, as these areas were likely underrepresented in NHANES. Finally, several studies have suggested that arsenic methylation patterns (including a higher proportion of methylarsonate in urine) and genetic susceptibility to arsenic health effects might be important to consider in the evaluation of arsenic related health effects.28,29
Because most participants had undetectable urine concentrations for arsenite, arsenate and methylarsonate, we were unable to evaluate the role of arsenic methylation patterns.