We performed conditional logistic regression to obtain estimates of relative risks and 95% confidence intervals associated with interquartile range (IQR) exposures from nephelometry (0.51 × 10-1 km-1 bsp) and PM10 (19.3 μg/m3). We conducted separate analyses for lags of 0 through 5 days since the induction period for an association between PM and out-of-hospital sudden cardiac arrest is unknown. We then selected a single lag for multipollutant models of PM with either CO or SO2. We examined effect modification by considering categories of selected variables, specifically age, current cigarette smoke exposure, aspirin use, consumption of alcoholic beverages, long-chain N-3 polyunsaturated fatty acid consumption, physical activity, and a composite of risk factors quantifying risk for coronary heart disease. We classified current cigarette smoke exposure as current smokers and subjects exposed to passive smoking for one or more hours in an average week. Aspirin use pertained to subjects taking the equivalent of two or more aspirin tablets per week. Alcoholic beverage consumers imbibed one or more alcoholic beverages per day. We classified subjects with consumption above the median of a Fish Intake Scale 25 along with those who reported taking fish oil supplements as exposed to long-chain N-3 polyunsaturated fatty acid. We classified cases as physically active if their average total kilocalories of recreational physical activity expended per week was greater than or equal to one. 33 For indications of coronary heart disease risk, we included treatment for diabetes mellitus, high blood total cholesterol, or hypertension, or family history of early myocardial infarction or sudden death (any parent or sibling experiencing myocardial infarction or sudden death before age 56 for males and before age 66 for females). We also assessed the role of time by examining effect modification by season and time categories (before or after the midpoint of the study period).
We assumed a linear exposure-effect model and estimated interquartile range relative risks and 95% confidence intervals for PM from light scattering for lags of 0 to 5 days. Effect estimates range from 0.89 (0 day lag; 95% CI = 0.78–1.02) to 1.01 (3 day lag; 95% CI = 0.90–1.12). We did not observe any pattern over the set of the lags suggestive of a relation between PM and the incidence of out-of-hospital primary cardiac arrest. The corresponding findings for PM10 display a generally similar pattern of no strong or consistent association with cardiac arrest. We selected lag 1 for subsequent analyses because, absent any compelling evidence for any other lag, it is the most proximal to the exposure among non-zero lags. At lag 0 we could not rule out that the time of the cardiac arrest may have preceded most of the exposure. We assessed the potential for a nonlinear exposure effect at lag 1 by estimating effects by quartile and by using regression spline smoothers with one and three knots. None of these models was an improvement over the linear exposure-effect model.
The possibility of detrimental health effects from particulate matter air pollution remains controversial. A large number of studies have found associations between PM and both morbidity and mortality outcomes. Most studies have linked daily variation in ambient PM concentrations to daily variation in total and cause-specific mortality, hospital admissions, or emergency department visits. For instance, Schwartz and Morris 11 observed an association between PM10 and hospital admissions for ischemic heart disease, congestive heart failure and dysrhythmias in Detroit, Michigan. Burnett et al.10 reported that fine sulfate particles were associated with heart disease admissions in Ontario, Canada. Schwartz 12 found associations between PM10 and cardiovascular disease admissions in Tucson, Arizona. He also observed that daily variation in PM10 was associated with hospital admissions for heart disease in eight US counties from various parts of the country, although the relation was weakest for Seattle among the eight metropolitan areas studied. 13 His summary relative risk estimate was 1.025 (95% confidence limits = 1.018, 1.032) for a 25 μg/m3 increase in PM10. He posited that approximately 5% of hospital admissions for heart disease may be attributable to air pollution.
Our results do not support an association between PM and out-of-hospital primary cardiac arrest. The patterns of results were nearly identical for PM measured by nephelometry and gravimetrically (PM10). Furthermore, we did not find evidence of effect modification by known personal risk factors for sudden cardiac arrest. Time-series studies of PM and cardiovascular disease are in the range of 1.4–4.2% increases in daily cardiovascular mortality for a 10 μg/m3 increase in PM10. 13,38 Because we have a refined endpoint, however, we expected a priori that the effect of PM on out-of-hospital primary cardiac arrest would show stronger associations. Instead, our results suggest there is no association between PM and out-of-hospital primary cardiac arrest.
The null findings were similar across the range of 0 to 5 day lags, although there were fluctuations of the effect estimates. While it is tempting to select the lag most consistent with our prior hypothesis of a positive effect, the plausibility of selected positive associations must be evaluated in the context of all the effects estimated. Otherwise, we introduce model selection bias into our reported results. 39 For instance, even though the point estimate of the relative risk for PM10 at lag 4 suggests an 8% increase in risk is possible, the lag 1 effect is even greater in absolute value, but for an inverse association. Furthermore, lag 1 represents the most plausible induction period for PM health effects on cardiac arrest a priori.
There are several plausible explanations for the absence of an observed effect of PM on risk of primary cardiac arrest in this case series. Our study relied on daily city-wide exposure measurements. Seattle is topographically diverse and has localized PM sources from wood burning, particularly in the winter. While we found location effects on PM levels that varied with atmospheric conditions in a small exposure substudy, a refined analysis accounting for measurement error did not suggest bias due to exposure misclassification masked an association in this study. 40 Furthermore, it may be possible that exposures in Seattle are overall of the wrong composition or too low to cause an effect. Supporting evidence comes from a time-series analysis from the same location and general time period. That study is consistent with these case-crossover results; it showed no elevated risks related to PM for cardiovascular and ischemic heart disease mortality. 41 Another explanation might be that the mechanisms of PM-related cardiovascular toxicity do not involve short-term triggers that culminate in cardiac arrest. The most likely explanation, however, relates to the highly select group of study subjects comprising our case series. They were free of major comorbidity and any history of clinical evidence of coronary artery disease. 25 In contrast, Peters et al42 studied patients implanted with cardioverter defibrillators to assess whether potentially life-threatening arrhythmias are associated with particulate air pollution episodes. They found an increase in NO2 was associated with increased tachycardia and ventricular fibrillation 2 days later, and that the most susceptible patients (those with repeated events) were especially at risk of experiencing arrhythmia after increases in PM2.5 and NO2. Together these two studies suggest that air pollution effects on the risk of potentially life-threatening arrhythmia are more plausible in susceptible individuals, eg, people with a history of severe cardiovascular disease.
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