Association of Long-Term Air Pollution with Ventricular Conduction and Repolarization Abnormalities

The 2010 American Heart Association consensus statement on air pollution and cardiovascular disease1 states that there is strong evidence that air pollution exposure contributes to a substantial public health burden of cardiovascular disease and death, although the specific mechanisms for these effects are poorly defined. One potential mechanism that has gained increasing support is an effect of air pollution on ventricular electrical activity, leading to cardiovascular morbidity and mortality. Ventricular electrical abnormalities – including QT interval prolongation, a measure of abnormal ventricular repolarization, and QRS widening, a measure of prolonged ventricular conduction – predict substantially increased risk of cardiovascular events in persons with and without clinical cardiovascular disease.2–4 Most studies of air pollution exposures and ventricular electrical activity have focused on short-term (hours to days) air pollution exposures,5–8 with relatively simple characterization of air pollution exposure at one monitoring site per study area. Despite this focus on short-term air pollution exposures and simple estimates of urban air pollution at single sites, epidemiologic cohorts suggest that long-term exposures that vary spatially within cities affect cardiovascular morbidity and mortality to a large extent,9 with risk estimates from such studies higher than those seen in large short-term time-series analyses.10 Although prior studies of air pollution-related effects have also focused primarily on repolarization using continuous measures of QT interval, measures of the presence of QT prolongation or QRS widening beyond specific thresholds that are associated with higher risk of cardiovascular events may represent changes more relevant to longer-term exposures than incremental increases in QT duration or QRS interval within the normal range. Because abnormalities of ventricular repolarization and conduction are associated with atherosclerosis, and because there is a growing body of evidence that long-term air pollution exposures are linked to atherosclerosis,11 an association between air pollution and cardiac electrical abnormalities may be mediated by the development of underlying atherosclerotic disease. Understanding how long-term air pollution exposure relates to cardiac electrical abnormalities, and whether such relationships appear to be mediated by atherosclerotic disease, may provide insight into the underlying mechanisms responsible for the associations. We hypothesized that long-term exposure to air pollution is associated with surface electrocardiogram (ECG) signs of abnormal ventricular electrical activity, independent of subclinical atherosclerosis. We aimed to test this hypothesis by examining long-term residential fine particulate matter exposure (less than 2.5 microns in mean aerodynamic diameter, PM2.5) measured at multiple locations and times in each study city, and its relation with prevalent ECG characteristics of QRS widening and QT prolongation. To determine whether any observed relationships might be mediated by subclinical atherosclerosis, we additionally aimed to evaluate the impact of adjusting for the presence of prevalent coronary artery calcium measured by cardiac computed tomography (CT). We also explored associations between such ECG findings and residential proximity to major roadways (a measure of exposure to traffic-related pollution). A large, multi-ethnic cohort (the Multi-Ethnic Study of Atherosclerosis, MESA) in six United States cities provided the foundation for testing these hypotheses. Participants were free of cardiovascular disease at entry, and with excellent measures of both exposure to particulate matter air pollution and subclinical atherosclerotic disease.