Association between Lifetime Exposure to Inorganic Arsenic in Drinking Water and Coronary Heart Disease in Colorado Residents

BACKGROUND: Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 mu g/L). However, associations have been inconclusive in populations with lower levels (< 100 mu g/L) of inorganic arsenic exposure. OBJECTIVES: We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD. METHODS: This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD. RESULTS: We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 mu g/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 mu g/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20-30 mu g/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30-45 mu g/L; and HR = 3, 95% CI: 1.1, 9.1 for 45-88 mu g/L). CONCLUSIONS: Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population.