Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study

Abstract

Background: Long-term exposure to high levels of arsenic is associated with increased risk for cardiovascular disease, whereas risk from long-term exposure to low to moderate arsenic levels (< 100μg/L in drinking water) is unclear.

Objective: To evaluate the association between long-term exposure to low to moderate arsenic levels and incident cardiovascular disease.

Design: Prospective cohort study.

Setting: The Strong Heart Study baseline visit between 1989 and 1991, with follow-up through 2008.

Patients: 3575 American Indian men and women aged 45 to 74 years living in Arizona, Oklahoma, and North and South Dakota.

Measurements: 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 cardiovascular disease.

Results: A total of 1184 participants developed fatal and nonfatal cardiovascular disease. When the highest and lowest quartiles of arsenic concentrations (> 15.7 vs. < 5.8 μg/g creatinine) were compared,the hazard ratios for cardiovascular disease, coronary heart disease, and stroke mortality after adjustment for sociodemographic factors, smoking, body mass index, and lipid levels were 1.65 (95%CI, 1.20 to 2.27; P for trend < 0.001), 1.71 (CI, 1.19 to 2.44; P for trend < 0.001), and 3.03 (CI, 1.08 to 8.50; P for trend = 0.061),respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, and stroke were 1.32 (CI,1.09 to 1.59; P for trend = 0.002), 1.30 (CI, 1.04 to 1.62; P for trend = 0.006), and 1.47 (CI, 0.97 to 2.21; P for trend = 0.032).These associations varied by study region and were attenuated after further adjustment for diabetes, hypertension, and kidney disease measures.

Limitation: Direct measurement of individual arsenic levels in drinking water was unavailable.

Conclusion: Long-term exposure to low to moderate arsenic levels was associated with cardiovascular disease incidence and mortality.

Figure 1. Hazard ratios for cardiovascular disease and coronary heart disease incidence and mortality by urine arsenic concentrations (N=3,575)

Solid lines represent adjusted hazard ratios based on restricted quadratic splines for log-transformed sum of inorganic and methylated arsenic species with knots at the 10^th, 50^th, and 90^th percentiles (3.8, 9.7, and 24.0 μg/g creatinine, respectively). Dotted lines represent upper and lower 95% confidence intervals. The reference was set at the 10^th percentile of the arsenic distribution (3.8 μg/g creatinine). Adjustment factors were the same as for Model 2 in Table 2 and 3. Vertical bars represent a histogram of urine arsenic distribution among participants (the extreme tails of the histogram were truncated as only 1 and 31 participant had urine arsenic levels <1.6 and >54.6 μg/g creatinine, respectively).

Figure 2. Hazard ratios for cardiovascular disease incidence and mortality stratified by study region

Solid lines represent adjusted hazard ratios based on restricted quadratic splines for log-transformed sum of inorganic and methylated arsenic species with knots at the 10^th, 50^th, and 90^th percentiles (3.8, 9.7, and 24.0 μg/g creatinine, respectively). Blue lines indicate participants in Arizona, red lines indicate participants from North/South Dakota, and green lines indicate participants from Oklahoma. The reference was set at the 10^th percentile of the arsenic distribution (3.8 μg/g creatinine). Adjustment factors were the same as for Model 2 in Table 2 and 3. Vertical bars represent a histogram of urine arsenic distribution among participants (the extreme tails of the histogram were truncated as only 1 and 31 participant had urine arsenic levels <1.6 and >54.6 μg/g creatinine, respectively).

Figure 3. Hazard ratios for cardiovascular disease incidence and mortality stratified by diabetes status

Solid lines represent adjusted hazard ratios based on restricted quadratic splines for log-transformed sum of inorganic and methylated arsenic species with knots at the 10^th, 50^th, and 90^th percentiles (3.8, 9.7, and 24.0 μg/g creatinine, respectively). Blue lines indicate participants with diabetes at baseline and red lines indicate participants without diabetes at baseline. The reference was set at the 10^th percentile of the arsenic distribution (3.8 μg/g creatinine). Adjustment factors were the same as for Model 2 in Table 2 and 3. Vertical bars represent a histogram of urine arsenic distribution among participants (the extreme tails of the histogram were truncated as only 1 and 31 participant had urine arsenic levels <1.6 and >54.6 μg/g creatinine, respectively).