as well as previous 12 and 24 hr moving aver- ages, of pollution concentration. Finally, mod- els containing multiple pollutant concentration as predictors were ﬁt to account for confound- ing due to moderate to high correlations among different pollutant concentrations. Multiple lags and moving averages were evaluated to select the best lag structure for temperature and each individual pollutant, and models reﬂect these evaluations. All statistical analyses were per- formed using the SAS statistical software pack- age (SAS Institute Inc., Cary, NC). The conditional linear mixed models were ﬁt using PROC MIXED, whereas the logistic mixed models were ﬁt using PROC NLMIXED (SAS Institute Inc.). Estimates of the effects of BC were scaled to the difference between the 10th and the 90th percentile in levels for the appropriate lag or mean value of BC. Results The median age of the population was 73, and many participants had cardiac risk factors (e.g., history of hypertension, prior smoking) or coronary artery disease (Table 1). As expected, mean heart rate rose during exercise and returned to baseline at rest (Table 2) during the 269 tests for the 24 participants included in analyses. Simultaneously, median ST-seg- ment level was lower during and immediately after exercise than at first rest. ST-segment depression was rare in the modiﬁed aVF lead, and all subsequent analyses are based on ﬁnd- ings in the modified V5 lead, the lead that most consistently identifies myocardial ischemia when it is present (Lanza et al. 1994). Air pollution levels were only modestly ele- vated, and maximum levels for U.S. EPA crite- ria pollutants were all below accepted or proposed National Air Quality Standards (Table 3). CO levels never exceeded 2 ppm. BC levels rose early in the morning and were at their peak between 0600 and 0900 hr. Individual hourly lag models showed consistent negative associations of ST-segment level with increased BC for the first 12 hr before testing (Figure 1), but with waning effects after 12 hr. The strongest association between BC and ST-segment level was for the 5-hr lagged value of BC (Table 4). For each portion of the protocol in the continuous models, higher 5-hr BC predicted lower between-test mean ST-segment levels. There was also a consistent effect of the mean of the BC levels during the 12 hr before testing on between-test ST-segment depression. Higher BC levels were also associated with lower between-test ST-segment levels, when averaged (for each individual, for each testing session) over all portions of the protocol (12-hr mean BC: estimated overall ST-segment change = –0.08 mm; p = 0.03; 5-hr BC: estimated change = –0.10 mm; p = 0.004), suggesting a pollution effect sustained throughout the pro- tocol. Although they were also consistently negative, associations of ST-segment depres- sion with the mean of BC during the 24-hr before testing were weaker, and the BC levels 2 days before testing had no association with ST-segment depression. There was no effect of air pollution on changes in ST-segment level from the rest to exercise or from the exercise to recovery portions of the protocol. The effects of BC on ST-segment depression were not modiﬁed by medication use, diagnosis of coronary artery disease, hypertension, sex, or ethnicity. For the smaller group who had at least 0.5 mm depression at one or more visits, increases in BC were associated with an elevated risk of ST-segment depression ≥ 0.5 mm, Table 3. Ambient pollution and temperature levels during Holter monitoring (n = 269).a 10th percentile 50th percentile 90th percentile Maximum 0.66 0.79 3.8 4.1 0.20 0.38 8.5 2.9 8.2 11.9 14.3 1.3 2.0 17.2 1.28 1.14 9.5 9.8 0.53 0.56 27.1 13.3 19.7 22.4 21.4 3.5 4.3 23.3 2.25 1.68 25.6 25.9 1.08 0.81 54.9 28.8 34.2 35.6 35.2 8.6 6.5 28.9 4.34 2.23 41.0 35.6 1.55 1.04 95.4 57.7 58.9 53.1 48.9 17.4 11.5 33.3 Pollutant BC (µg/m3) 5-hrb 12-hr meanc PM 2.5 (µg/m3) 5-hrb 12-hr mean CO (ppm) 5-hrb 12-hr mean O3 (ppb) 1-hr 5-hrb 12-hr mean NO2 (ppb) 5-hrb 12-hr mean SO2 (ppb) 5-hrb 12-hr mean Temperature (°C) aPollutants include daily BC, PM2.5, O3, NO2, SO2, and CO. Temperature is current 1-hr mean. bThe distribution of the levels (totaln = 269) during the ﬁfth hour before Holter monitoring. cThe mean of the levels during the 24 hr before Holter monitoring. Environmental Health Perspectives • VOLUME 113 | NUMBER 7 | July 2005 Air pollution and ST-segment depression although conﬁdence in the estimates was lim- ited by the smaller numbers of observations (Table 4). The largest estimated risk occurred during the rest period immediately after exer- cise, when there was a 10.4-fold risk [95% con- fidence interval (CI), 1.3–83.0] of having between-test ST-segment depression ≥ 0.5 mm. Although CO was associated with ST-segment depression in single-pollutant models, in mul- tiple-pollution models only BC remained asso- ciated with ST-segment depression (Table 5). Discussion In elderly subjects, we found that increases in levels of ambient BC in the 12 hr before testing were associated with between-week depression in the mean ST-segment levels that was present throughout the testing ses- sion, with the strongest effects occurring in the postexercise recovery portions of the pro- tocol, a period of cardiac vulnerability in patients with coronary artery disease (Frolkis et al. 2003). There was no effect of pollution on within-testing session changes in the mag- nitude of ST-segment depression. The risk of ST-segment depression of ≥ 0.5 mm was elevated with higher pollution; new ECG depression of this magnitude has been associ- ated with increased risk of adverse cardiac events among patients with acute coronary syndrome (Cannon et al. 1997). Although we found pollution to be associ- ated with ST-segment depression sustained throughout the testing session, the Finnish portion of the ULTRA study found associa- tions of pollution with reversible exercise- induced ST-segment depression (Pekkanen et al. 2002). The etiology of the ST-segment depression we observed is unclear but may represent the consequences of subclinical myocardial ischemia, inﬂammation, or both. Although a minority of our subjects had documented coronary disease, many had risk factors predisposing them to subclinical dis- ease and possible ischemia. Particle pollution may decrease myocardial oxygen supply and increase the risk of cardiac ischemia due to t ne 0.05 egm ihng -s t 0 TS rae n b o d–0.05 tc ce fe a fe ,)p–0.10 tedCB l(emm–0.15 a v itm le–0.20 s E 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Log (hr) Figure 1. Estimates of the effects of BC on mean ST-segment level during paced breathing, scaled to the difference between the 10th and the 90th percentile in levels for individual hourly lags. Error bars indicate 95% CIs. 885