Association Between Exposure to Low to Moderate Arsenic Levels and Incident Cardiovascular Disease: A Prospective Cohort Study

Study Questions:

Is long-term exposure to low to moderate levels of arsenic associated with increased cardiovascular disease (CVD) risk?

Methods:

This current analysis used data from the Strong Heart Study, a prospective cohort study with baseline visits between 1989 and 1991, and follow-up through 2008 in 3,575 American Indian adults ages 45-74 years. All participants were living in Arizona, Oklahoma, and North and South Dakota. The sum of inorganic and methylated arsenic species in urine at baseline was used as a biomarker of long-term arsenic exposure. Outcomes were incident fatal and nonfatal CVD.

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).

Conclusions:

The investigators concluded that long-term exposure to low to moderate arsenic levels was associated with CVD incidence and mortality.

Perspective:

The data from this study suggest that even at low levels, arsenic is associated with increased CVD risk.

Keywords: Follow-Up Studies, Coronary Disease, Risk Factors, Prevalence, Incidence, Biological Markers, South Dakota, Arsenic Poisoning, Cardiology, Oklahoma, Cardiovascular Diseases, Indians, North American, Risk Assessment


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