Kirsi L. Timonen

Particulate Air Pollution and Risk of ST-Segment Depression During Repeated Submaximal Exercise Tests Among Subjects With Coronary Heart Disease The Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air (ULTRA) Study

Background—Daily variations in ambient particulate air pollution have been associated with cardiovascular mortality and morbidity. We therefore assessed the associations between levels of the 3 main modes of urban aerosol distribution and the occurrence of ST-segment depressions during repeated exercise tests. Methods and Results—Repeated biweekly submaximal exercise tests were performed during 6 months among adult subjects with stable coronary heart disease in Helsinki, Finland. Seventy-two exercise-induced ST-segment depressions >0.1 mV occurred during 342 exercise tests among 45 subjects. Simultaneously, particle mass <2.5 &mgr;m (PM2.5) and the number concentrations of ultrafine particles (particle diameter 10 to 100 nm [NC0.01–0.1]) and accumulation mode particles (100 to 1000 nm [NC0.1–1]) were monitored at a central site. Levels of particulate air pollution 2 days before the clinic visit were significantly associated with increased risk of ST-segment depression during exercise test. The association was most consistent for measures of particles reflecting accumulation mode particles (odds ratio 3.29; 95% CI, 1.57 to 6.92 for NC0.1–1 and 2.84; 95% CI, 1.42 to 5.66 for PM2.5), but ultrafine particles also had an effect (odds ratio 3.14; 95% CI, 1.56 to 6.32), which was independent of PM2.5. Also, gaseous pollutants NO2 and CO were associated with an increased risk for ST-segment depressions. No consistent association was observed for coarse particles. The associations tended to be stronger among subjects who did not use &bgr;-blockers. Conclusions—The present results suggest that the effect of particulate air pollution on cardiovascular morbidity is at least partly mediated through increased susceptibility to myocardial ischemia.

Personal exposure to fine particulate matter in elderly subjects : Relation between personal, indoor, and outdoor concentrations

ABSTRACT The time-series correlation between ambient levels, indoor levels, and personal exposure to PM2.5 was assessed in panels of elderly subjects with cardiovascular disease in Amsterdam, the Netherlands, and Helsinki, Finland. Subjects were followed for 6 months with biweekly clinical visits. Each subjects indoor and personal exposure to PM2.5 was measured biweekly, during the 24-hr period preceding the clinical visits. Outdoor PM2.5 concentrations were measured at fixed sites. The absorption coefficients of all PM2.5 filters were measured as a marker for elemental carbon (EC). Regression analyses were conducted for each subject separately, and the distribution of the individual regression and correlation coefficients was investigated. Personal, indoor, and ambient concentrations were highly correlated within subjects over time. Median Pearsons R between personal and outdoor PM2.5 was 0.79 in Amsterdam and 0.76 in Helsinki. For absorption, these values were 0.93 and 0.81 for Amsterdam and Helsinki, respectively. The findings of this study provide further support for using fixed-site measurements as a measure of exposure to PM2.5 in epidemiological time-series studies.

Effects of ultrafine and fine particulate and gaseous air pollution on cardiac autonomic control in subjects with coronary artery disease : The ULTRA study

Previous studies have shown an association between elevated concentrations of particulate air pollution and cardiovascular morbidity and mortality. Therefore, the association between daily variation of ultrafine and fine particulate air pollution and cardiac autonomic control measured as heart rate variability (HRV) was studied in a large multicenter study in Amsterdam, the Netherlands, Erfurt, Germany, and Helsinki, Finland. Elderly subjects (n=37 in Amsterdam, n=47 in both Erfurt and Helsinki) with stable coronary artery disease were followed for 6 months with biweekly clinical visits. During the visits, ambulatory electrocardiogram was recorded during a standardized protocol including a 5-min period of paced breathing. Time and frequency domain analyses of HRV were performed. A statistical model was built for each center separately. The mean 24-h particle number concentration (NC) (1000/cm3) of ultrafine particles (diameter 0.01–0.1 μm) was 17.3 in Amsterdam, 21.1 in Erfurt, and 17.0 in Helsinki. The corresponding values for PM2.5 were 20.0, 23.1, and 12.7 μg/m3. During paced breathing, ultrafine particles, NO2, and CO were at lags of 0–2 days consistently and significantly associated with decreased low-to-high frequency ratio (LF/HF), a measure of sympathovagal balance. In a pooled analysis across the centers, LF/HF decreased by 13.5% (95% confidence interval: −20.1%, −7.0%) for each 10,000/cm3 increase in the NC of ultrafine particles (2-day lag). PM2.5 was associated with reduced HF and increased LF/HF in Helsinki, whereas the opposite was true in Erfurt, and in Amsterdam, there were no clear associations between PM2.5 and HRV. The results suggest that the cardiovascular effects of ambient ultrafine and PM2.5 can differ from each other and that their effect may be modified by the characteristics of the exposed subjects and the sources of PM2.5.

Can We Identify Sources of Fine Particles Responsible for Exercise-Induced Ischemia on Days with Elevated Air Pollution? the ULTRA Study

Epidemiologic studies have shown that ambient particulate matter (PM) has adverse effects on cardiovascular health. Effective mitigation of the health effects requires identification of the most harmful PM sources. The objective of our study was to evaluate relative effects of fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] from different sources on exercise-induced ischemia. We collected daily outdoor PM2.5 samples between autumn 1998 and spring 1999 in Helsinki, Finland. The mass of PM2.5 was apportioned between five sources. Forty-five elderly nonsmoking persons with stable coronary heart disease visited a clinic biweekly for submaximal exercise testing, during which the occurrence of ST segment depressions was recorded. Levels of PM2.5 originating from local traffic and long-range transport were associated with ST segment depressions > 0.1 mV, with odds ratios at 2-day lag of 1.53 [95% confidence interval (CI), 1.19–1.97] and 1.11 (95% CI, 1.02–1.20) per 1 μg/m3, respectively. In multipollutant models, where we used indicator elements for sources instead of source-specific PM2.5, only absorbance (elemental carbon), an indicator of local traffic and other combustion, was associated with ST segment depressions. Our results suggest that the PM fraction originating from combustion processes, notably traffic, exacerbates ischemic heart diseases associated with PM mass.

Associations between PM2.5 and heart rate variability are modified by particle composition and beta-blocker use in patients with coronary heart disease.

Background It has been hypothesized that ambient particulate air pollution is able to modify the autonomic nervous control of the heart, measured as heart rate variability (HRV). Previously we reported heterogeneous associations between particulate matter with aerodynamic diameter < 2.5 μm (PM2.5) and HRV across three study centers. Objectives We evaluated whether exposure misclassification, effect modification by medication, or differences in particle composition could explain the inconsistencies. Methods Subjects with coronary heart disease visited clinics biweekly in Amsterdam, the Netherlands; Erfurt, Germany; and Helsinki, Finland for 6–8 months. The standard deviation (SD) of NN intervals on an electrocardiogram (ECG; SDNN) and high frequency (HF) power of HRV was measured with ambulatory ECG during paced breathing. Outdoor levels of PM2.5 were measured at a central site. In Amsterdam and Helsinki, indoor and personal PM2.5 were measured during the 24 hr preceding the clinic visit. PM2.5 was apportioned between sources using principal component analyses. We analyzed associations of indoor/personal PM2.5, elements of PM2.5, and source-specific PM2.5 with HRV using linear regression. Results Indoor and personal PM2.5 were not associated with HRV. Increased outdoor PM2.5 was associated with decreased SDNN and HF at lags of 2 and 3 days only among persons not using beta-blocker medication. Traffic-related PM2.5 was associated with decreased SDNN, and long-range transported PM2.5 with decreased SDNN and HF, most strongly among persons not using beta blockers. Indicators for PM2.5 from traffic and long-range transport were also associated with decreased HRV. Conclusions Our results suggest that differences in the composition of particles, beta-blocker use, and obesity of study subjects may explain some inconsistencies among previous studies on HRV.

Stability over time of short-term heart rate variability

Heart rate variability (HRV) is a widely used method to assess cardiac autonomic control. However, the reproducibility of especially short-term HRV has not been properly evaluated. Therefore, we assessed the stability of short-term HRV over a three to four month period. We had seven consecutive electrocardiographic (ECG) recordings from 89 subjects with stable coronary artery disease obtained during a large multicenter study. The HRV assessments were performed from these 40-minute ECG-recordings simulating normal daily activities, i. e., recordings consisting of 5 to 10 minute periods of rest, paced breathing, standing, submaximal exercise and recovery. Both time and frequency domain HRV analyses were conducted from the whole 40-minute recordings and from the 5-minute periods of rest and paced breathing. The coefficient of variation (CV) varied between 5.1–16.7% for the 40-minute and 6.0–37.1% for the 5-minute time domain and 4.4–11.0 % for the 40-minute and 7.2–16.5 % for the 5-minute frequency domain measurements. The mean of the RR intervals and the total power showed the highest stability over time. The most unstable measure was the standard deviation of all NN intervals (SDNN). In conclusion, most short-term HRV measures were highly stable over time indicating low physiological variation. However, the SDNN showed large variability in consecutive recordings.

Hourly variation in fine particle exposure is associated with transiently increased risk of ST segment depression

Objectives: To evaluate whether hourly changes in fine particle (PM2.5, diameter<2.5 µm) exposure or outdoor particle concentrations are associated with rapid ischaemic responses. Methods: 41 non-smoking elderly people with coronary heart disease were followed up with biweekly clinic visits in Helsinki, Finland. The occurrence of ST segment depressions >0.1 mV was recorded during submaximal exercise tests. Hourly variations in personal PM2.5 exposure and outdoor levels of PM2.5 and ultrafine particles (<0.1 µm) were recorded for 24 h before a clinic visit. Associations between particulate air pollution and ST segment depressions were evaluated using logistic regression. Results: Both personal and outdoor PM2.5 concentrations, but not outdoor ultrafine particle counts, were associated with ST segment depressions. The odds ratio (per 10 µg/m3) for personal PM2.5 concentration during the hour preceding a clinic visit was 3.26 (95% CI 1.07 to 9.99) and for 4 h average outdoor PM2.5 it was 2.47 (95% CI 1.05 to 5.85). Conclusions: Even very short-term elevations in fine particle exposure might increase the risk of myocardial ischaemia. The precise mechanism is still unknown but could involve changes in autonomic nervous control of the heart.

Daily variation in fine and ultrafine particulate air pollution and urinary concentrations of lung Clara cell protein CC16

Background: Daily variations in ambient particulate air pollution have been associated with respiratory mortality and morbidity. Aims: To assess the associations between urinary concentration of lung Clara cell protein CC16, a marker for lung damage, and daily variation in fine and ultrafine particulate air pollution. Methods: Spot urinary samples (n = 1249) were collected biweekly for six months in subjects with coronary heart disease in Amsterdam, Netherlands (n = 37), Erfurt, Germany (n = 47), and Helsinki, Finland (n = 47). Ambient particulate air pollution was monitored at a central site in each city. Results: The mean 24 hour number concentration of ultrafine particles was 17.3×103 cm−3 in Amsterdam, 21.1×103 cm−3 in Erfurt, and 17.0×103 cm−3 in Helsinki. The mean 24 hour PM2.5 concentrations were 20, 23, and 13 μg/m3, respectively. Daily variation in ultrafine particle levels was not associated with CC16. In contrast, CC16 concentration seemed to increase with increasing levels of PM2.5 in Helsinki, especially among subjects with lung disorders. No clear associations were observed in Amsterdam and Erfurt. In Helsinki, the CC16 concentration increased by 20.2% (95% CI 6.9 to 33.5) per 10 μg/m3 increase in PM2.5 concentration (lag 2). The respective pooled effect estimate was 2.1% (95% CI −1.3 to 5.6). Conclusion: The results suggest that exposure to particulate air pollution may lead to increased epithelial barrier permeability in lungs.

Effect of acute carbon monoxide exposure on heart rate variability in patients with coronary artery disease

Epidemiological studies have shown that air pollution is associated with increased cardiovascular mortality. Although the pathophysiological mechanisms behind this association have remained largely unknown, it has been suggested that changes in cardiac autonomic function may play a role. In this study, we investigated the association between acute carbon monoxide (CO) exposure and cardiac autonomic function as measured by heart rate variability (HRV) in subjects with stable coronary artery disease. Twenty‐four hour ambulatory electrocardiographic recording with simultaneous continuous personal CO concentration monitoring was performed in six male patients with angiographically verified coronary artery disease three times with 1‐week intervals. Time domain measures of HRV were calculated for 5‐min segments before and during the CO exposure periods. For further analysis CO exposures were divided into low (≤2·7 p.p.m.) and high (>2·7 p.p.m.) CO exposure periods. The mean of maximum CO levels during 61 CO exposure periods was 4·6 p.p.m. (SD 5·0 p.p.m.). High CO exposure was associated with an increase in the square root of the mean of the sum of the squares of differences between adjacent RR intervals (r‐MSSD) (P = 0·034). Heart rate remained unchanged during the CO exposure. In conclusion, acute CO exposure which represented most likely exposure derived from traffic seems to modify cardiac autonomic control in patients with stable coronary artery disease.

Effects of air pollution on changes in lung function induced by exercise in children with chronic respiratory symptoms

Objective: To investigate how daily variations in ambient air pollution, especially in particles, during the cold of winter affect repeated measurements of baseline lung function and exercise induced bronchial responsiveness among primary school children with chronic respiratory symptoms. Methods: During alternate school weeks (mamimum five) from February to April 1994, 33 children took part in exercise challenge tests (n=141 tests). The exercise challenges were conducted outdoors in a school yard in the centre of Kuopio, Finland. Spirometric lung functions were measured indoors before the exercise, and 3 and 10 minutes after. Daily mean concentrations of PM10, black smoke (BS), NO2, CO, SO2, and particle size and numbers were monitored at a nearby fixed monitoring site. Results: Daily variations in ambient air pollution were not associated with enhanced bronchial responsiveness. However, increased concentrations of BS, PM10, particle numbers, NO2, and CO were consistently associated with an impairment of baseline lung functions. The reductions in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were 0.5% and 0.6%, respectively, for each 10 μg/m3 increase in BS (lag 2). Conclusion: Particles derived from combustion affect baseline lung function rather than bronchial responsiveness among children with chronic respiratory symptoms.