Results:

Over 45,738 person-years of follow-up, 439 participants died of cardiovascular disease (341 coronary heart disease deaths and 54 stroke deaths) and 1,184 participants developed fatal or nonfatal CVD (846 incident coronary heart disease events and 264 incident strokes). The median urinary arsenic concentration was 9.7 µg/g creatinine (interquartile range, 5.8-15.7 µg/g creatinine; range, 0.1-183.4 µg/g creatinine). Urinary arsenic concentrations varied by study region; the medians were 14.2, 5.6, and 10.6 µg/g creatinine in Arizona, Oklahoma, and the Dakotas, respectively. Increasing baseline arsenic concentrations were associated with female sex, lower educational attainment, lower low-density lipoprotein cholesterol level, higher estimated glomerular filtration rate, increased prevalence of never-smokers, and increased prevalence of diabetes. When the highest and lowest quartiles of arsenic concentrations (>15.7 vs. <5.8 µg/g creatinine) were compared, the hazard ratios for CVD, coronary heart disease, and stroke mortality after adjustment for sociodemographic factors, smoking, body mass index, and lipid levels were 1.65 (95% confidence interval [CI], 1.20-2.27; p for trend < 0.001), 1.71 (CI, 1.19-2.44; p for trend < 0.001), and 3.03 (CI, 1.08-8.50; p for trend < 0.061), respectively. The corresponding hazard ratios for incident CVD, coronary heart disease, and stroke were 1.32 (CI, 1.09-1.59; p for trend < 0.002), 1.30 (CI, 1.04-1.62; p for trend < 0.006), and 1.47 (CI, 0.97-2.21; p for trend < 0.032).