Uranium exposure in drinking water and cardiovascular disease in the Strong Heart Study

PROJECT SUMMARY Uranium (U) is a naturally occurring element potentially associated with cardiovascular health outcomes. Across the United States (US), U is released into the environment through wind and water erosion, as well as anthropogenic mining, milling and other forms of U processing. Importantly, U is ubiquitous in American Indian

(AI) communities, where the cardiovascular disease (CVD) burden remains disproportionally high, and U exposure via drinking water remains a concern. While the maximum contaminant level (MCL) for U in public water systems (30 µg/L) took effect in 2008, no MCL was regulated in the US prior to this time, and AI

communities relying on private wells for drinking water are not regulated. The Strong Heart Study (SHS), a prospective study of CVD among AI communities in North Dakota, South Dakota, Arizona and Oklahoma, represents an important population to understand the extent and impact of U exposure on health outcomes. This

requires a comprehensive assessment of both water and internal dose U exposure, including U measured in urine. However, urinary U data is only available in a kinship-based extension of the SHS, those comprising the Strong Heart Family Study (SHFS), and there is need to estimate this exposure across the entire SHS community

to identify those with elevated U exposure and determine the long-term health outcomes. The objectives of this study are to 1) estimate water U exposure in SHS and SHFS participants relying on existing nationwide groundwater measurements, 2) estimate urinary U concentrations in SHS participants leveraging the

associations between drinking water U and urinary U concentrations in the SHFS, and 3) investigate if estimated U exposure (water and urinary) in the SHS and SHFS is linked to CVD outcomes, both overall, and according to participant region and other characteristics. Water U exposure estimations (Aim 1) will rely on community water

system estimations of U concentrations derived from the US EPA, the National Uranium Resource Evaluation Hydrogeochemical and Stream Sediment Reconnaissance database, which includes 335,547 sampling locations across the contiguous US collected from 1975 to 1980; the USGS National Water Information System, which

provides water-resources data on over 1.9 million sites across the US; the Strong Heart Water Study, a pilot study of household water U measures (n = 441); and the USGS Reconnaissance study. These datasets will be used to assign water U measures to household locations. For Aim 2, the relationship between estimated water

U exposure and urinary U concentrations in SHFS will be used to predict urinary U values in SHS participants with machine learning approaches. For Aim 3, we will investigate the association between estimated water and urinary U concentrations with both clinical and subclinical cardiovascular outcomes in SHS and SHFS

participants. This work will estimate U exposure across the entire SHS, identify populations at increased risk of U-related CVD outcomes, and inform interventions to reduce water U exposure in AI communities and other communities equally affected by U exposure across the US.