Arsenic Exposure from Drinking Water and QT-Interval Prolongation: Results from the Health Effects of Arsenic Longitudinal Study

Abstract

Background: Arsenic exposure from drinking water has been associated with heart disease; however, underlying mechanisms are uncertain.Objective: We evaluated the association between a history of arsenic exposure from drinking water and the prolongation of heart rate–corrected QT (QTc), PR, and QRS intervals.Method: We conducted a study of 1,715 participants enrolled at baseline from the Health Effects of Arsenic Longitudinal Study. We assessed the relationship of arsenic exposure in well water and urine samples at baseline with parameters of electrocardiogram (ECG) performed during 2005–2010, 5.9 years on average since baseline.Results: The adjusted odds ratio (OR) for QTc prolongation, defined as a QTc ≥ 450 msec in men and ≥ 460 msec in women, was 1.17 (95% CI: 1.01, 1.35) for a 1-SD increase in well-water arsenic (108.7 µg/L). The positive association appeared to be limited to women, with adjusted ORs of 1.24 (95% CI: 1.05, 1.47) and 1.24 (95% CI: 1.01, 1.53) for a 1-SD increase in baseline well-water and urinary arsenic, respectively, compared with 0.99 (95% CI: 0.73, 1.33) and 0.86 (95% CI: 0.49, 1.51) in men. There were no apparent associations of baseline well-water arsenic or urinary arsenic with PR or QRS prolongation in women or men.Conclusions: Long-term arsenic exposure from drinking water (average 95 µg/L; range, 0.1–790 µg/L) was associated with subsequent QT-interval prolongation in women. Future longitudinal studies with repeated ECG measurements would be valuable in assessing the influence of changes in exposure.

Arsenic and the Cardiovascular System

“…The elevated risk of females to As-induced QT prolongation was also reported by Chen et al [100] in a study evaluating the effects of long-term As exposure from drinking water (0.1-790 μg/L). Another study, where the authors performed a cross-sectional analysis in elderly men in Boston, MA, between 2000 and 2002 or in 2006 from the Normative Aging Study to analyze associations between toenail arsenic and QT/QTc durations using linear regression, found the interquartile range increase in arsenic concentration was associated with a 3.8 ms increase in QT (95% confidence interval: 0.82, 6.8) and a 2.5 ms increase in QTc (95% confidence interval: 0.11, 4.9) [101].…”

Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

“…Additional studies suggest that arsenic impacts endothelial function, reactive oxygen signaling and levels of inflammatory mediators [38–41]. Further, arsenic has been associated with prolonged QT interval duration, a risk factor for sudden cardiac death, in studies from high and lower exposure areas [42,43], including the US-based Normative Aging Study [44]. …”

Environmental factors in cardiovascular disease

“…[188][189][190] Chronic arsenic exposure is also associated with changes in cardiac electrophysiology, such as QT-interval prolongation, which is a risk factor for sudden cardiac death. 178,191,192 Although many of these mechanisms have been evaluated at high levels of exposure, evidence suggests that effects such as neovascularization, angiogenesis, and vessel remodelling occur at relatively low levels of exposure, even below the current maximum contaminant level for drinking water.…”