Air pollution and ST-segment depression in elderly subjects

Environmental Health Perspectives, July, 2005 by Diane R. Gold, Augusto A. Litonjua, Antonella Zanobetti, Brent A. Coull, Joel Schwartz, Gail MacCallum, Richard L. Verrier, Bruce D. Nearing, Marina J. Canner, Helen Suh, Peter H. Stone

Although a minority of our subjects had documented coronary disease, many had risk factors predisposing them to subclinical disease and possible ischemia. Particle pollution may decrease myocardial oxygen supply and increase the risk of cardiac ischemia due to epicardial coronary disease through potentially interrelated mechanisms, including systemic inflammation, oxidative stress, endothelial dysfunction, and/or autonomic dysfunction (Gold et al. 2000; Liao et al. 1999). Coronary artery disease is now considered, in large part, an inflammatory process (Ridker et al. 2000), and transient increases in air pollution could lead to transient exacerbation in vascular inflammation. Particle pollution has been linked to ST-segment changes in healthy canines (Godleski et al. 2000) and to reduction of the time to ischemic changes in canines with partial coronary artery occlusion (Wellenius et al. 2003). Brachial artery diameter, which is correlated with coronary artery diameter, was diminished in healthy subjects after exposure in a chamber to concentrated ambient particles (Brook et al. 2002), concomitant with elevated levels of endothelin.

Rather than causing subclinical ischemia, pollution-associated systemic inflammation may lead to low-grade myocardial inflammation, with associated subtle repolarization changes, including sustained ST-segment depression. A series of epidemiologic studies have found associations of particle pollution with elevation of measures of systemic inflammation, including plasma viscosity (Peters et al. 1997), fibrinogen (Gardner et al. 2000), neutrophil count, vascular cellular adhesion molecule and soluble intracellular adhesion molecule (Salvi et al. 1999), and C-reactive protein (Peters et al. 2001).

In this same study, in the entire cohort, we found that BC was associated with a decrease in heart rate variability, suggesting traffic-particle-associated autonomic dysfunction (Schwartz et al. In press). Future work will focus on whether ambient pollution leads to ST-segment depression and autonomic dysregulation through related pathways (e.g., inflammation) or through separate pathways.

BC can be viewed as a surrogate for traffic-related particle pollution; exhaust emissions from diesel-powered vehicles have been identified as the main source of BC or elemental carbon in urban areas (Janssen et al. 2002; Schauer et al. 1996). Laden et al. (2000), in a study of six U.S. cities, found that traffic particles were more strongly associated with cardiovascular deaths than were particles from coal burning. Although BC influenced ST-segment depression, we did not find independent effects of CO on ST-segment level, perhaps because of the low levels of exposure. In one study, short-term exposure to CO, producing carboxyhemoglobin levels of 2-3.9%, were associated with ischemic ST-segment changes in exercising subjects with coronary disease (Allred et al. 1989), although these low-level effects were not reproduced in a study by Sheps et al. (1987). ST-segment depression during exercise was associated with [PM.sub.2.5] and CO in the Finnish study of subjects with stable coronary heart disease who performed repeated biweekly submaximal exercise tests over a 6-month period (Pekkanen et al. 2002). In that study, correlation between the two pollutants made it more difficult to separate their effects. In our Boston setting, CO was not an independent predictor of ST-segment depression. An alternative explanation for the lack of independent associations of the gases with ST-segment depression is more misclassification of exposure, particularly because all the gases other than CO were measured at distances farther than the site where BC and [PM.sub.2.5] were measured, which was very close to the health effects testing site (discussed above).