A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh.

BACKGROUND

Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk.

OBJECTIVE

We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk.

METHOD

We conducted a case-cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS).

RESULTS

The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity--indicated by higher urinary MMA% or lower urinary DMA%--with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking.

CONCLUSIONS

Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk.