Academic journal article Environmental Health Perspectives

Traffic-Related Air Pollution and QT Interval: Modification by Diabetes, Obesity, and Oxidative Stress Gene Polymorphisms in the Normative Aging Study

Academic journal article Environmental Health Perspectives

Traffic-Related Air Pollution and QT Interval: Modification by Diabetes, Obesity, and Oxidative Stress Gene Polymorphisms in the Normative Aging Study

Article excerpt

BACKGROUND: Acute exposure to ambient air pollution has been associated with acute changes in cardiac outcomes, often within hours of exposure.

OBJECTIVES: We examined the effects of air pollutants on heart-rate-corrected QT interval (QTc), an electrocardiographic marker of ventricular repolarization, and whether these associations were modified by participant characteristics and genetic polymorphisms related to oxidative stress.

METHODS: We studied repeated measurements of QTc on 580 men from the Veterans Affairs Normative Aging Study (NAS) using mixed-effects models with random intercepts. We fitted a quadratic constrained distributed lag model to estimate the cumulative effect on QTc of ambient air pollutants including fine particulate matter [less than or equal to] 2.5 [micro]m in aerodynamic diameter ([PM.sub.2.5]), ozone ([O.sub.3]), black carbon (BC), nitrogen dioxide ([NO.sub.2]), carbon monoxide (CO), and sulfur dioxide ([SO.sub.2]) concentrations during the 10 hr before the visit. We genotyped polymorphisms related to oxidative stress and analyzed pollution--susceptibility score interactions using the genetic susceptibility score (GSS) method.

RESULTS: Ambient traffic pollutant concentrations were related to longer QTc. An interquartile range (IQR) change in BC cumulative during the 10 hr before the visit was associated with increased QTc [1.89 msec change; 95% confidence interval (CI),-0.16 to 3.93]. We found a similar association with QTc for an IQR change in 1-hr BC that occurred 4 hr before the visit (2.54 msec change; 95% CI, 0.28-4.80). We found increased QTc for IQR changes in [NO.sub.2] and CO, but the change was statistically insignificant. In contrast, we found no association between QTc and [PM.sub.2.5]. [SO.sub.2], and [O.sub.3]. The association between QTc and BC was stronger among participants who were obese, who had diabetes, who were nonsmokers, or who had higher GSSs.

CONCLUSIONS: Traffic-related pollutants may increase QTc among persons with diabetes, persons who are obese, and nonsmoking elderly individuals; the number of genetic variants related to oxidative stress increases this effect.

KEYWORDS: air pollution, diabetes, distributed lags, genes, obesity, oxidative stress, QT interval, smoking, traffic. Environ Health Perspect 118:840-846 (2010). doi:10.1289/ehp.0901396 [Online 1 March 2010]

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Evidence from epidemiologic studies shows a consistent association between increased ambient air pollution and increased daily hospital admission (Lee et al. 2007; Santos et al. 2008; Schwartz 1999; Zanobetti and Schwartz 2006) and premature death (Pope et al. 2004; Schwartz 1994). Studies have further shown that the pollution-mediated impacts were largest for cardiovascular-related illness and deaths (von Klot et al. 2009; Zanobetti and Schwartz 2007). Several biological mechanisms by which air pollution can elicit cardiovascular morbidity and mortality have been identified, including oxidative stress (Gurgueira et al. 2002), autonomic dysfunction (Gold et al. 2000), and systemic inflammation (Peters et al. 2001b; Ruckerl et al. 2006), leading to endothelial dysfunction (O'Neill et al. 2005), atheromatous plaque (Sun et al. 2005; Suwa et al. 2002), and thrombosis (Baccarelli et al. 2008). However, the specific underlying biological pathways are not fully understood, and the identification of these pathways warrants further study.

Of particular interest arc recent studies that suggest that myocardial infarctions risk (Peters et al. 2001a, 2004), inflammation (Ruckerl et al. 2006), and cardiac repolarization changes (Henneberger et al. 2005; Yue et al. 2007) may be associated with exposures to air pollution on time scales of less than a day. Because standards for particles and nitrogen dioxide ([NO.sub.2]) currently involve longer-term averages, these studies suggest that the relation of hourly peaks in air pollution with indicators or cardiovascular health should be examined. …

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