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. 2018 Sep:240:894-902.
doi: 10.1016/j.envpol.2018.04.129. Epub 2018 May 26.

Association of low-moderate urine arsenic and QT interval: Cross-sectional and longitudinal evidence from the Strong Heart Study

Katherine A Moon  1 , Yiyi Zhang  2 , Eliseo Guallar  2 , Kevin A Francesconi  3 , Walter Goessler  3 , Jason G Umans  4 , Lyle G Best  5 , Barbara V Howard  4 , Richard B Devereux  6 , Peter M Okin  6 , Ana Navas-Acien  7
Affiliations

Association of low-moderate urine arsenic and QT interval: Cross-sectional and longitudinal evidence from the Strong Heart Study

Katherine A Moon et al. Environ Pollut. 2018 Sep.

Abstract

Epidemiologic studies suggest that chronic exposure to arsenic is related to cardiovascular disease (CVD), but the pathophysiological link remains uncertain. We evaluated the association of chronic low-moderate arsenic exposure and arsenic metabolism with baseline difference and annual change in ECG measures (QT interval, JT interval, PR interval, QRS duration, and QT dispersion) using linear mixed models in the Strong Heart Study main cohort (N = 1174, median age 55 years) and family study (N = 1695 diabetes-free, median age 36 years). At baseline, arsenic exposure was measured as the sum of inorganic and methylated species in urine (ΣAs) and arsenic metabolism was measured as the relative percentage of arsenic species. Median ΣAs and Bazett heart rate-corrected QT interval (QTc) were 8.6 μg/g creatinine and 424 ms in the main cohort and 4.3 μg/g and 414 ms in the family study, respectively. In the main cohort, a comparison of the highest to lowest ΣAs quartile (>14.4 vs. <5.2 μg/g creatinine) was associated with a 5.3 (95% CI: 1.2, 9.5) ms higher mean baseline QTc interval but no difference in annual change in QTc interval. In the family study, a comparison of the highest to lowest quartile (>7.1 vs. <2.9 μg/g creatinine) was associated with a 3.2 (95% CI: 0.6, 5.7) ms higher baseline QTc interval and a 0.6 (95% CI: 0.04, 1.2) ms larger annual increase in QTc interval. Associations with JTc interval were similar but stronger in magnitude compared to QTc interval. Arsenic exposure was largely not associated with PR interval, QRS duration or QT dispersion. Similar to arsenic exposure, a pattern of lower %MMA and higher %DMA was associated with longer baseline QTc interval in both cohorts and with a larger annual change in QTc interval in the family study. Chronic low-moderate arsenic exposure and arsenic metabolism were associated with prolonged ventricular repolarization.

Keywords: Arsenic; Cardiovascular disease; Electrocardiology; Longitudinal cohort; QT interval; Ventricular repolarization.

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Figures

Figure 1.
Figure 1.. Difference in baseline QTc-B interval by restricted cubic splines of log-transformed baseline urine arsenic in Strong Heart Study main cohort participants and Strong Heart Family Study participants without diabetes
Solid lines are the adjusted mean differences in baseline QTc-B interval by baseline urine arsenic concentrations, in relation to the 10th percentile of urine arsenic (3.5 in the main cohort, and 2.2 μg/g creatinine in the family study). Shaded areas represent the 95% confidence intervals of the adjusted mean differences. Mean differences were estimated from a linear mixed model with fixed effects for restricted cubic splines of log-transformed arsenic (knots at the 10th, 50th, and 90th percentiles), time (years from baseline), interactions between arsenic terms and time, and baseline age (years), sex, education (no, some, or finished high school), smoking (never, former, current), alcohol drinking (never, former, current), body mass index (kg/m2), low density lipoprotein (LDL) cholesterol (mg/dL), hypertension (yes/no), estimated glomerular filtration rate (eGFR; mL/min/1.73 m2), and study center (Arizona, Oklahoma, North and South Dakota), and random effects for subject and time (years from baseline).
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