Research | Environmental Medicine Air Pollution and ST-Segment Depression in Elderly Subjects Diane R. Gold,1,2 Augusto A. Litonjua,1 Antonella Zanobetti,2 Brent A. Coull,3 Joel Schwartz,2 Gail MacCallum,4 Richard L. Verrier,5 Bruce D. Nearing,5 Marina J. Canner,1 Helen Suh,6 and Peter H. Stone 4 1Channing Laboratory, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 2Environmental Epidemiology Program, Department of Environmental Health, and 3Environmental Statistics Program, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA; 4Cardiology Division, Brigham and Women’s Hospital, Department of Medicine, Boston, Massachusetts, USA; 5Division of Cardiology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 6Environmental Science and Engineering Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the trafﬁc-related component of parti- cles. We investigated associations between ambient pollution and ST-segment levels in a repeated- measures study including 269 observations on 24 active Boston residents 61–88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During post- exercise rest, an elevated BC level was associated with –0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression ≥ 0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inﬂammation, is associated with increased exposure to particles whose predominant source is trafﬁc. Key words: air pollution, cardiology, elderly, particles, ST-segment depression, trafﬁc. Environ Health Perspect 113:883–887 (2005). doi:10.1289/ehp.7737 available via http://dx.doi.org/ [Online 14 March 2005] Numerous studies have demonstrated asso- ciations of acute increases in particle levels with increased risk of cardiac morbidity and mortal- ity (Pope et al. 1995). Efforts have been directed toward understanding mechanisms for these associations. Canine studies showing increased risk of myocardial ischemia (Wellenius et al. 2003) and a chamber study showing decreased brachial artery diameter with particle exposure (Brook et al. 2002) have provided supportive evidence for particle-induced ischemia as a potential mechanism. Both carbon monoxide and particle mass < 2.5 µg/m3 (PM2.5) were associated with increased risk of ST-segment depression during repeated submaximal exer- cise tests among subjects with coronary heart disease in 45 adults with stable coronary heart disease in Helsinki, Finland (Pekkanen et al. 2002); PM2.5 was believed to be the primary source of this association, but because of cor- relation with CO, the authors reported that independent effects were difﬁcult to separate. Black carbon (BC) may be a more precise measure than PM2.5 of the portion of particle mass related to trafﬁc (Laden et al. 2000). We examined whether there were independent associations of the ambient traffic-associated pollutants, BC and CO, with ST-segment depression before and after submaximal exercise in a community-based repeated-measures study of elderly adults from Boston, Massachusetts. Materials and Methods Study design and protocol. We recruited a panel of elderly subjects living at or near an apartment complex located within 1 km of a central site monitoring station. A baseline screening questionnaire was administered regarding medications, pulmonary and car- diac symptoms, and smoking history. A rest- ing 12-lead electrocardiogram (ECG) was performed. Exclusion criteria included unsta- ble angina, atrial ﬂutter, atrial ﬁbrillation, or paced rhythm. Each subject was assigned a day of the week and a time of day for weekly testing, with the goal of 12 weekly visits dur- ing the summer of 1999. Each week, partici- pants were administered a brief questionnaire regarding chest pain, medication changes, and whether medications had been taken that morning. Continuous Holter monitoring with electrodes in a modiﬁed V5 and aVF position was performed using the Marquette Seer Digital Recorder (Marquette Inc., Milwaukee, WI). The protocol (Gold et al. 2000) consisted of a) 5 min rest, b) 5 min standing, c) 5 min exercise outdoors (if the participant felt able, a standard walk was performed, involving one climb up a slight incline), d) 4 min supine recovery, or e) 3 min 20 sec slow, paced breath- ing (for each of 20 respiratory cycles, the par- ticipant was asked to breathe in for 5 sec and then out for 5 sec, coached by a technician). Environmental Health Perspectives • VOLUME 113 | NUMBER 7 | July 2005 Processing of Holter recordings. The digital Holter recordings were downloaded to a MARS Ultra 60 playback system (Marquette Inc.) for analysis. ST-segments were evaluated for the average value for each portion of the protocol and for possible ischemia, defined as reversible horizontal or downsloping ST- segment depression ≥ 0.5 mm, a level associ- ated with adverse cardiac risk in patients with acute coronary syndrome (Cannon et al. 1997). Recordings were visually scanned by an experienced analyst to censor artifacts. Custom algorithms were created to calculate the aver- age “ST-segment level” or value, referenced to the P-R isoelectric values, for each portion of the protocol. Separately, each candidate episode of reversible ST-segment deviation was evaluated as possibly representing ischemia, by using real-time ECG strips examined by an experienced analyst and physician blinded to air pollution status. A table of J-point values, ST-segment values, ST-segment slope, and heart rate was printed for each candidate episode beginning 10 min before each episode and ending 10 min after the resolution of each episode. The ST-segment value 60 msec after the J-point was used to deﬁne the ST-segment deviation and the ST-segment slope. Air pollution measurements. Air pollution measurements (PM2.5, BC, CO) were col- lected at a central site within 0.5 km of the res- idences of the subjects, which were on the same busy street trafﬁcked by diesel-powered buses and trucks as well as cars of commuters. Measurements of sulfur dioxide, ozone, and nitrogen dioxide were obtained from state monitoring sites in Boston. Continuous PM2.5 was measured using a tapered element oscil- lating microbalance (TEOM; model 1400A; Rupprecht and Patashnick, Albany, NY). Address correspondence to D.R. Gold, Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, 181 Longwood Ave., Boston, MA 02215 USA. Telephone: (617) 525-2738. Fax: (617) 525-0950. E-mail: diane.gold@channing.harvard.edu This work was supported in part by National Institutes of Health grant 5 P01 ES09825, U.S. Environmental Protection Agency (EPA) Cooperative Agreement CR821762, EPA 826780-01-0, and EPA R827353-01-0. The authors declare they have no competing ﬁnan- cial interests. Received 8 November 2004; accepted 14 March 2005. 883