Arsenic-Induced QT Dispersion is Associated with Atherosclerotic Diseases and Predicts Long-Term Cardiovascular Mortality in Subjects with Previous Exposure to Arsenic: A 17-Year Follow-Up Study

Abstract

Chronic arsenic poisoning is a major worldwide public health problem. Recently, we had reported chronic arsenic poisoning was dose-dependently associated with ventricular abnormalities quantified by electrocardiographic QT prolongation linking to atherosclerotic diseases. An association of chronic arsenic poisoning with ventricular repolarization inhomogeneity quantified by QT dispersion (QTD) is of particular interest from a theoretical and practical perspective. We aimed to further elucidate (1) the association of chronic arsenic exposure with ventricular abnormalities quantified by QTD, (2) the association of QTD with atherosclerotic diseases and (3) the predictability of QTD for long-term mortality in subjects with chronic arsenic poisoning. We followed up 280 men and 355 women living in arseniasis-endemic area in southwestern coast in Taiwan for 17 years. QTD in electrocardiogram and carotid intima-media thickness by ultrasonography were measured. Coronary artery disease was diagnosed by an abnormal electrocardiogram and a definite history. Cumulative arsenic exposure was significantly associated with QTD showing a dose-response relationship (P < 0.001). Significant associations of the QTD with coronary artery disease and carotid atherosclerosis existed after adjustment for potential confounders in the multiple linear regression analysis (all P values < 0.05). In the multivariate Cox regression analyses, the hazard ratios (95% confidence interval, P value) of cumulative cardiovascular and all-cause mortality were 3.9 (2.1-6.2, P = 0.002) and 1.4 (0.9-2.3, P = 0.10), respectively, for QTD > or = 65 ms compared with QTD < 65. QTD may be indicated as an early biomarker for atherosclerotic diseases and a significant and strong predictor of cardiovascular mortality in population with chronic arsenic exposure.

Cardiovascular effects of arsenic: clinical and epidemiological findings

“…Consistent with the association with risk factors and CV disease, an association has also been found between As exposure and atherosclerosis (Wang et al 2002;Wang et al 2010;Hsieh et al 2011), and confirmed in experimental animal studies (Bunderson et al 2004;Srivastava et al 2009;Lemaire et al 2011). …”

“…As exposure in a wide range of levels is consistently associated with QT prolongation -a risk factor for arrhythmia and sudden cardiac death -torsade de pointes (Ficker et al 2004;Mumford et al 2007;Mordukhovich et al 2009;Wang et al 2009), and increased QT dispersion (Wang et al 2010). As may act on QT by increasing cardiac calcium currents (Ficker et al 2004), but no protective effect of calcium-antagonists has been found (Mordukhovich et al 2009) and there are conflicting data on verapamil enhancing or reducing As cardiotoxicity (Zhao et al 2008a;Luong and Rabkin 2009).…”

The Evaluation of the Ameliorative Effect of Montelukast Against Arsenic Trioxide-Induced Cardiotoxicity in Rats

“…Consistent with the current result,s an epidemiological study on Taiwanese cases living in an arsenic-exposed region demonstrated a direct correlation between QT prolongation in ECG pattern and tissue arsenic concentration (23). In another study, the prevalence of QTc prolongation in arsenic-exposed people was reported as 90% (24) and the underlying mechanisms of arsenic cardiotoxicity have been suggested as excessive generation of oxygen free radicals and oxidative stress (6,24).…”

Arsenic and human health effects: A review

“…Changes in duration of QT-interval either short or prolonged have shown association with increased sudden cardiac death due to the development of malignant ventricular arrhythmias (Zhang et al, 2011). Many recent studies have shown strong association between arsenic exposure via drinking water and QT prolongation Mordukhovich et al, 2009;Mumford et al, 2007;Wang et al, 2009a) and dose dependent chronic arsenic exposure increased QT/QTc depression linking to atherosclerotic diseases (Wang et al, 2010). Crucially, low arsenic levels have shown a positive tendency to alter QT interval duration (Mordukhovich et al, 2009).…”