Abstract
The underlying pathology of arsenic-related cardiovascular disease (CVD) is unknown. Few studies have evaluated pathways through thrombosis and inflammation for arsenic-related CVD, especially at low-moderate arsenic exposure levels (<100 μg/L in drinking water). We evaluated the association of chronic low-moderate arsenic exposure, measured as the sum of inorganic and methylated arsenic species in urine (ΣAs), with plasma biomarkers of thrombosis and inflammation in American Indian adults (45–74 years) in the Strong Heart Study. We evaluated the cross-sectional and longitudinal associations between baseline ΣAs with fibrinogen at three visits (baseline, 1989–91; Visit 2, 1993–95, Visit 3, 1998–99) using mixed models and the associations between baseline ΣAs and Visit 2 plasminogen activator inhibitor-1 (PAI-1) and high sensitivity C-reactive protein (hsCRP) using linear regression. Median (interquartile range) concentrations of baseline ΣAs and fibrinogen, and Visit 2 hsCRP and PAI-1 were 8.4 (5.1, 14.3) μg/g creatinine, 346 (304, 393) mg/dL, 44 (30, 67) mg/L, and 3.8 (2.0, 7.0) ng/mL, respectively. Comparing the difference between the 75th and the 25th percentile of ΣAs (14.3 vs. 5.1 μg/g creatinine), ΣAs was positively associated with baseline fibrinogen among those with diabetes (adjusted geometric mean ratio (GMR): 1.05, 95% CI: 1.02, 1.07) not associated among those without diabetes (GMR: 1.01, 95% CI: 0.99, 1.02) (p-interaction for diabetes = 0.014), inversely associated with PAI-1 (GMR: 0.94, 95% CI: 0.90, 0.99), and not associated with hsCRP (GMR: 1.00, 95% CI: 0.93, 1.08). We found no evidence for an association between baseline ΣAs and annual change in fibrinogen over follow-up (p-interaction = 0.28 and 0.12 for diabetes and non-diabetes, respectively). Low-moderate arsenic exposure was positively associated with baseline fibrinogen in participants with diabetes and unexpectedly inversely associated with PAI-1. Further research should evaluate the role of prothrombotic factors in arsenic-related cardiovascular disease.
Highlights
Almost five million people in the United States (US) drink water from public and private wells with arsenic concentrations above US Environmental Protection Agency (EPA) standard of 10 μg/L [1,2,3,4], and millions more are exposed below this level
In the Strong Heart Study (SHS) main cohort, a population of adult men and women exposed to low-moderate levels of arsenic in drinking water (
Further adjustment for albuminuria and hemoglobin A1c, which may act as confounders or mediators of the association between arsenic and cardiovascular disease (CVD) [58, 59], attenuated the association with fibrinogen but did not change the association with PAI-1
Summary
Almost five million people in the United States (US) drink water from public and private wells with arsenic concentrations above US Environmental Protection Agency (EPA) standard of 10 μg/L [1,2,3,4], and millions more are exposed below this level. Drinking water and food are important sources of inorganic arsenic exposure in populations with low levels of arsenic in drinking water [4,5,6,7,8]. Epidemiological studies of populations with high (!100 μg/L) [9,10,11], and low-moderate (
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