The association of arsenic exposure and arsenic metabolism with all-cause, cardiovascular and cancer mortality in the Strong Heart Study.

The effect of low-moderate levels of arsenic exposure and of arsenic metabolism on mortality remains uncertain. We used data from a prospective cohort study in 3600 men and women aged 45 to 75 years living in Arizona, Oklahoma, and North and South Dakota. The biomarker of inorganic arsenic exposure was the sum of urine inorganic (iAs), monomethylated (MMA) and dimethylated (DMA) arsenic compounds (ƩAs) at baseline. The proportions of urine iAs, MMA and DMA over the ƩiAs, expressed as iAs%, MMA%, and DMA%, respectively, were used as biomarkers of arsenic metabolism. Arsenic exposure and arsenic metabolism were associated with all-cause, cardiovascular, and cancer mortality. For each interquartile range (IQR) increase in ƩAs (12.5 μg/L, overall range 0.7-194.1 μg/L), the adjusted hazard ratios (aHRs) were 1.28 (95% CI 1.16-1.41) for all-cause mortality, 1.28 (1.08-1.52) for cardiovascular mortality and 1.15 (0.92-1.44) for cancer mortality. The aHR for mortality for each IQR increase in MMA%, when iAs% is decreasing, was 1.52 (95% CI 1.16-1.99) for cardiovascular disease, 0.73 (0.55-0.98) for cancer, and 1.03 (0.90-1.19) for all-cause mortality. These findings at low-moderate levels of arsenic exposure highlight the need to implement public health measures to protect populations from involuntary arsenic exposure and for research to advance the biological and clinical understanding of arsenic-related health effects in general populations.