from diesel-powered vehicles have been identi- fied 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 parti- cles were more strongly associated with cardio- vascular 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 PM2.5 and CO in the Finnish study of subjects with sta- ble 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 pol- lutants made it more difﬁcult to separate their effects. In our Boston setting, CO was not an independent predictor of ST-segment depres- sion. 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 far- ther than the site where BC and PM2.5 were measured, which was very close to the health effects testing site (discussed above). This study was limited by lack of personal exposure measurements for CO and particles. However, ambient levels were measured on the same busy city street as the participant res- idences, < 0.5 km away, and studies in Boston have shown that ambient concentrations are good surrogates of personal exposures to PM2.5 of ambient origin (Rojas-Bracho et al. 2000). Moreover, the consequence of using Table 5. 5-hr BC and CO as predictors of continuous ST-segment level in single- and multiple-pollutant models. Outcome variable, model Predictor variable Coefﬁcient Estimated effect [mm (95% CI)] p-Value Second rest 1 2 3 4 5 6 7 Paced breathing 1 2 3 4 5 6 7 207 209 196 257 233 219 90 (29)c 66 (22) 66 (28) 114 (38) 90 (48) 66 (22) Table 4. Ambient BC as a predictor of ST-segment level for ﬁve protocol periods. 0.001 0.007 0.04 0.45 0.92 0.39 0.22 0.53 0.001 0.05 0.01 0.87 0.64 0.60 0.33 0.30 0.03 0.03 0.09 0.57 0.03 0.02 0.11 0.11 0.06 0.53 0.19 0.15 BC CO BC CO PM2.5 O3 NO2 SO2 BC CO BC CO PM2.5 O3 NO2 SO2 –0.11 (–0.20 to –0.02) –0.09 (–0.16 to –0.01) –0.11 (–0.21 to –0.01) –0.08 (–0.17 to 0.00) –0.11 (–0.18 to –0.05) –0.11 (–0.17 to –0.04) 5.1 (0.9 to 28.0) 6.0 (0.8 to 44.8) 9.2 (1.1 to 78.3) 0.9 (0.2 to 4.7) 10.4 (1.3 to 83.0) 6.6 (0.9 to 50.0) –0.07 –0.15 –0.06 –0.05 –0.0002 1.38 –1.96 –3.19 –0.07 –0.11 –0.07 0.01 –0.0008 0.85 –1.54 –5.15 0.02 0.02 0.03 0.06 0.001 0.001 0.06 0.07 0.05 0.86 0.03 0.06 –0.11 (–0.17 to –0.05) –0.13 (–0.22 to –0.04) –0.09 (–0.17 to 0.03) –0.05 (–0.17 to 0.07) –0.004 (–0.08 to 0.07) 0.04 (–0.05 to 0.12) –0.05 (–0.12 to 0.03) –0.02 (–0.10 to 0.05) –0.11 (–0.17 to –0.04) –0.09 (–0.19 to 0.00) –0.11 (–0.20 to –0.03) 0.01 (–0.11 to 0.13) –0.02 (–0.09 to 0.05) 0.02 (–0.06 to 0.11) –0.04 (–0.11 to 0.04) –0.04 (–0.11 to 0.03) –0.10 (–0.19 to –0.01) –0.08 (–0.15 to –0.01) –0.09 (–0.19 to 0.01) –0.02 (–0.11 to 0.06) –0.07 (–0.14 to –0.01) –0.08 (–0.14 to –0.01) 3.8 (0.7 to 21.3) 5.7 (0.6 to 56.3) 8.3 (0.8 to 81.9) 0.6 (0.1 to 3.1) 2.8 (0.5 to 14.3) 3.5 (0.5 to 23.6) Gold et al. epicardial coronary disease through poten- tially interrelated mechanisms, including systemic inﬂammation, oxidative stress, endo- thelial dysfunction, and/or autonomic dys- function (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 diam- eter, 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), con- comitant with elevated levels of endothelin. Rather than causing subclinical ischemia, pollution-associated systemic inflammation may lead to low-grade myocardial inflam- mation, 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 inﬂam- mation, 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 dysfunc- tion (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 Outcome variable Estimated ST-segment change in mm (95% CI), for continuous outcomeb First rest Blood pressure Standing Exercise Second rest Paced breathing Estimated relative risk (95% CI), for ST-segment depression ≥ 0.5 mm First rest Blood pressure Standing Exercise Second rest Paced breathing 886 Repeated-measures regression models contain pollution concentration, a cubic effect of current temperature, and a linear trend of time. All models except model 3 include only the single pollutant described. Model 3, for second rest and for paced breathing, includes both BC and CO; thus, the coefﬁcient for BC is adjusted for CO. Results presented are estimated for a 10th to 90th percentile change in BC. No. of observations 5-hr BCa p-Value 12-hr mean BCa p-Value aEstimated for a 10th to 90th percentile change in BC. bRepeated-measures regression models contain pollution concentration, a cubic effect of current temperature, and a linear trend of time. cNumbers in parentheses in this column represent the number of positive events with ST-depression ≥ 0.5 mm. VOLUME 113 | NUMBER 7 | July 2005 • Environmental Health Perspectives