In this study of 203 New England Medical Center ICD patients living in the Boston metropolitan area with up to 7 years of follow-up, we found the risk of any ICD-detected ventricular tachyarrhythmia was positively but not significantly associated with increased exposure to air pollution on the days before the arrhythmia (). We found statistically significant associations of air pollution with increased risk of ventricular arrhythmias among patients with an arrhythmia within the previous 3 days. These findings suggest that air pollution may provoke ventricular tachyarrhythmias only in the presence of acutely predisposing conditions that increase ventricular electrical instability. We did not find consistent indications that the air pollution associations with ventricular arrhythmias were modified by indicators of chronically impaired cardiac function, including a prior myocardial infarction, a diagnosis of coronary artery disease, or an ejection fraction < 35%, or by prescribed antiarrhythmic medications.
These results are broadly consistent with those of previously published studies of air pollution associations with tachyarrhythmias leading to ICD therapeutic discharge. In this study, we found significantly increased risk of ventricular arrhythmias with PM2.5
, BC, CO, NO2
, and SO2
among patients with a recent rior ventricular arrhythmia. In the pilot study (Peters et al. 2000
), ICD patients in Boston with frequent (> 10) discharges during follow-up had an exposure related increase in ICD discharge associated with PM2.5
, BC, CO, and NO2
A recent study assessed the association of air pollution in Vancouver, British Columbia, Canada, with ICD discharges among 50 patients with an average of 2.2 years of follow-up (Rich et al. 2004
; Vedal et al. 2004
). In crude analyses, the rate of ICD discharge increased with quartiles of NO2
and CO concentration on the same day (Vedal et al. 2004
). However, there were no statistically significant positive associations with ICD discharge with NO2
or CO after adjusting for temporal patterns and numerous weather parameters. The lack of significant associations may be caused by overcontrol of some variables, as these investigators suggest.
Both of these previously reported studies (Peters et al. 2000
; Vedal et al. 2004
) focused on ICD therapeutic discharge without characterization or validation of the underlying arrhythmia. Of the almost 2,000 arrhythmias identified and recorded by the ICD devices in this study, 8% were classified as oversensing, 4% were sinus tachycardias, 18% were supra-ventricular arrhythmias, and 70% were ventricular arrhythmias. Thus, 30% of the ICD-detected arrhythmias were not the potentially life-threatening ventricular tachyarrhythmias defined as the primary outcome for this study.
An important question in these analyses is the appropriate exposure averaging time and the lag between exposure and cardiac arrhythmia. In the pilot study, we found associations with air pollutants 2 days before the arrhythmias and with the 5-day mean air pollution (Peters et al. 2000
). In this study, ventricular arrhythmias were positively associated with ambient air pollution on the same and the previous calendar days. Temporality would require that air pollution exposure precede the arrhythmia. This temporal association is clearly true for associations with air pollution on the previous day, but mean air pollution on the same calendar day would include hours after as well as before the detected arrhythmia. Using the pollutant concentrations from the specific 24 hr preceding the arrhythmia would likely provide a better estimate of each subject’s exposure and allow investigation of exposures in the hours before the arrhythmia.
For these patients living in eastern Massachusetts, air pollution exposure was estimated based on a single or a small number of monitors in the Boston metropolitan area. This would lead to misclassification of air pollution exposure, but this misclassification would be independent of the risk for ventricular arrhythmias. Such nondifferential misclassification of exposure produces an attenuated estimate of associations (and larger CIs) in epidemiologic studies assuming linear associations. If these observations are true, then studies with improved estimation of subject specific air pollution exposures would be expected to find stronger, more statistically significant associations.
We found associations with CO, NO2, BC, and PM2.5. These four pollutants had high day-to-day correlations with each other and were strongly correlated with SO2. It would not be possible to differentiate the independent effects of these pollutants. Nevertheless, the associations with these specific pollutants are consistent with an effect from air pollution from motor vehicle sources.
Animal studies in Boston have suggested that changes in indicators of cardiac function are specifically associated with motor vehicle pollution (Clarke et al. 2000
). Analysis of daily mortality in Boston and five other cities suggested that motor vehicle pollution was more strongly related to cardiovascular mortality than to respiratory mortality (Laden et al. 2000
). Cardiovascular emergency department visits in Atlanta, Georgia, were significantly associated with these same markers of motor vehicle air pollution—NO2
, CO, PM2.5
, BC, and fine particle organic carbon (Metzger et al. 2004
). For Atlanta emergency department visits for dysrhythmias, positive associations were found for these same motor vehicle pollutants, although these associations were not statistically significant because of the smaller number of events.
We cannot exclude the possible role of sulfur oxides, which are generally considered to be indicators of air pollution from power plants and other stationary fossil fuel combustion sources. In this analysis, we found associations of ventricular tachyarrhythmias in subjects with a recent event associated with SO2 (p = 0.013) and with SO4 (p = 0.06). The positive, marginally significant associations with SO4 are notable because SO4 data were available only on a limited number of days (37%) compared with SO2 and the other gaseous pollutants. Particulate SO4 concentrations in Boston largely reflect secondary particles formed during long-range transport. Gaseous SO2 concentrations reflect local sulfur emissions and were most highly correlated with motor vehicle pollutants.
A major advantage of the ICD data is the passive monitoring of cardiac tachyarrhythmias. Nevertheless, ICD-detected ventricular arrhythmias were rare events in this follow-up, and the small number of subjects with multiple ICD-detected arrhythmias is a limitation. These patients clearly represent a highly selected cohort of special interest, because their previous history of cardiovascular disease might make them particularly sensitive to the effects of air pollution episodes. The observed associations of ventricular tachyarrhythmias with particulate air pollution in these subjects are large compared with previous studies. In a mortality time-series analysis in Boston and five other cities (Schwartz et al. 1996
), each increase of 10 μg/m3 in the 2-day mean PM2.5
was associated with a 2% increase in the risk of cardiovascular mortality. For Boston ICD patients (), the observed associations imply an 11% (95% CI, –9 to 35%) increased risk of potentially fatal ventricular arrhythmias when scaled to the same 10 μg/m3
in the 2-day mean PM2.5
concentrations. Thus, the ICD patients had a risk of potentially life-threatening ventricular tachyarrhythmias associated with fine particles that was more than five times the risk of cardiovascular death in the general population. Among those at the highest risk—those with a recent prior ventricular arrhythmia—the increased risk of a new ventricular tachyarrhythmia was 97% (95% CI, 46–165%) associated with each 10-μg/m3
increase in PM2.5