Urinary Arsenic and Cadmium Associations with Findings from Cranial MRI in American Indians: Data from the Strong Heart Study

BACKGROUND: Arsenic and cadmium are known cardiovascular toxicants that pose disproportionate risk to rural communities where environmental exposures are high. American Indians have high vascular risk, which may be attributable in part to these exposures. OBJECTIVE: We examined urine metal concentrations in association with magnetic resonance imaging findings of vascular brain injury or cerebral atrophy in adult American Indians. METHODS: We measured arsenic and cadmium in American Indian participants from the Strong Heart Study (1989-1991) and evaluated these associations with later (2010-2013) measures of infarct, hemorrhage, white matter hyperintensity (WMH) grade, brain and hippocampal volume, and sulcal and ventricle atrophy using nested multivariate regression analyses. RESULTS: Among participants with available data (N = 687), the median urine arsenic:creatinine ratio was 7.54 mu g/g [interquartile range (IQR): 4.90-11.93] and the cadmium:creatinine ratio was 0.96 mu g/g (IQR: 0.61-1.51). Median time between metal measurement and brain imaging was 21 y (range: 18-25 y). Statistical models detected significant associations between arsenic and higher burden of WMH [grade increase = 0.014 (95% CI: 0.000, 0.028) per 10% increase in arsenic]; and between cadmium and presence of lacunar infarcts [relative risk (RR) = 1.024 (95% CI: 1.004, 1.045) per 10% increase in cadmium]. DISCUSSION: This population-based cohort of American Indian elders had measured values of urine arsenic and cadmium several times higher than previous population- and clinic-based studies in the United States and Mexico, and comparable values with European industrial workers. Our findings of associations for arsenic and cadmium exposures with vascular brain injury are consistent with established literature. Environmental toxicant accumulation is modifiable; public health policy may benefit from focusing on reductions in environmental metals.