Detection of prostate cancer bone metastases with fast whole-body 99mTc-HMDP SPECT/CT using a general-purpose CZT system.

BACKGROUND: We evaluated the effects of acquisition time, energy window width, and matrix size on the image quality, quantitation, and diagnostic performance of whole-body 99mTc-HMDP SPECT/CT in the primary metastasis staging of prostate cancer. METHODS: Thirty prostate cancer patients underwent 99mTc-HMDP SPECT/CT from the top of the head to the mid-thigh using a Discovery NM/CT 670 CZT system with list-mode acquisition, 50-min acquisition time, 15% energy window width, and 128 × 128 matrix size. The acquired list-mode data were resampled to produce data sets with shorter acquisition times of 41, 38, 32, 26, 20, and 16 min, narrower energy windows of 10, 8, 6, and 4%, and a larger matrix size of 256 × 256. Images were qualitatively evaluated by three experienced nuclear medicine physicians and quantitatively evaluated by noise, lesion contrast and SUV measurements. Diagnostic performance was evaluated from the readings of two experienced nuclear medicine physicians in terms of patient-, region-, and lesion-level sensitivity and specificity. RESULTS: The originally acquired images had the best qualitative image quality and lowest noise. However, the acquisition time could be reduced to 38 min, the energy window narrowed to 8%, and the matrix size increased to 256 × 256 with still acceptable qualitative image quality. Lesion contrast and SUVs were not affected by changes in acquisition parameters. Acquisition time reduction had no effect on the diagnostic performance, as sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve were not significantly different between the 50-min and reduced acquisition time images. The average patient-level sensitivities of the two readers were 88, 92, 100, and 96% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 78, 84, 84, and 78%. The average region-level sensitivities of the two readers were 55, 58, 59, and 56% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 95, 98, 96, and 95%. The number of equivocal lesions tended to increase as the acquisition time decreased. CONCLUSION: Whole-body 99mTc-HMDP SPECT/CT can be acquired using a general-purpose CZT system in less than 20 min without any loss in diagnostic performance in metastasis staging of high-risk prostate cancer patients.

Comparison of reprojected bone SPECT/CT and planar bone scintigraphy for the detection of bone metastases in breast and prostate cancer.

OBJECTIVE: The aim of this study was to compare reprojected bone SPECT/CT (RBS) against planar bone scintigraphy (BS) in the detection of bone metastases in breast and prostate cancer patients. METHODS: Twenty-six breast and 105 prostate cancer patients with high risk for bone metastases underwent 99mTc-HMDP BS and whole-body SPECT/CT, 1.5-T whole-body diffusion-weighted MRI and 18F-NaF or 18F-PSMA-1007 PET/CT within two prospective clinical trials (NCT01339780 and NCT03537391). Consensus reading of all imaging modalities and follow-up data were used to define the reference standard diagnosis. The SPECT/CT data were reprojected into anterior and posterior views to produce RBS images. Both BS and RBS images were independently double read by two pairs of experienced nuclear medicine physicians. The findings were validated against the reference standard diagnosis and compared between BS and RBS on the patient, region and lesion levels. RESULTS: All metastatic patients detected by BS were also detected by RBS. In addition, three metastatic patients were missed by BS but detected by RBS. The average patient-level sensitivity of two readers for metastases was 75% for BS and 87% for RBS, and the corresponding specificity was 79% for BS and 39% for RBS. The average region-level sensitivity of two readers was 64% for BS and 69% for RBS, and the corresponding specificity was 96% for BS and 87% for RBS. CONCLUSION: Whole-body bone SPECT/CT can be reprojected into more familiar anterior and posterior planar images with excellent sensitivity for bone metastases, making additional acquisition of planar BS unnecessary.

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

BACKGROUND: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). OBJECTIVE: To compare standard staging modalities with newer and potentially more accurate imaging modalities. DESIGN, SETTING, AND PARTICIPANTS: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. RESULTS AND LIMITATIONS: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. CONCLUSIONS: Despite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. PATIENT SUMMARY: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.

Reference values of inspiratory spirometry for Finnish adults.

Inspiratory spirometry is used in evaluation of upper airway disorders e.g. fixed or variable obstruction. There are, however, very few published data on normal values for inspiratory spirometry. The main aim of this study was to produce reference values for inspiratory spirometry for healthy Finnish adults. Inspiratory spirometry was preplanned to a sample of the Finnish spirometry reference values sample. Data was successfully retrieved from 368 healthy nonsmoking adults (132 males) between 19 and 83 years of age. Reference equations were produced for forced inspiratory vital capacity (FIVC), forced inspiratory volume in one second (FIV1), FIV1/FIVC, peak inspiratory flow (PIF) and the ratios of FIV1/forced expiratory volume in one second and PIF/peak expiratory flow. The present values were compared to PIF values from previously used Finnish study of Viljanen et al. (1982) reference values and Norwegian values for FIV1, FIVC and FIV1/FIVC presented by Gulsvik et al. (2001). The predicted values from the Gulsvik et al. (2001), provided a good fit for FIVC, but smaller values for FIV1 with mean 108.3 and 109.1% of predicted values for males and females, respectively. PIF values were 87.4 and 91.2% of Viljanen et al. (1982) predicted values in males and females, respectively. Differences in measurement methods and selection of results may contribute to the observed differences. Inspiratory spirometry is technically more demanding and needs repeatability criteria to improve validity. New reference values are suggested to clinical use in Finland when assessing inspiratory spirometry. Utility of inspiratory to expiratory values indices in assessment of airway collapse need further study.

Reference values for pulmonary diffusing capacity for adult native Finns.

Measurement standards for pulmonary diffusing capacity were updated in 2005 by the ATS/ERS Task Force. However, in Finland reference values published in 1982 by Viljanen et al. have been used to date. The main aim of this study was to produce updated reference models for single-breath diffusing capacity for carbon monoxide for Finnish adults. Single-breath diffusing capacity for carbon monoxide was measured in 631 healthy non-smoking volunteers (41.5% male). Reference values for diffusing capacity (DLCO), alveolar volume (VA), diffusing capacity per unit of lung volume (DLCO/VA), and lung volumes were calculated using a linear regression model. Previously used Finnish reference values were found to produce too low predicted values, with mean predicted DLCO 111.0 and 104.4%, and DLCO/VA of 103.5 and 102.7% in males and females, respectively. With the European Coalition for Steel and Coal (ECSC) reference values there was a significant sex difference in DLCO/VA with mean predicted 105.4% in males and 92.8% in females (p < .001). New reference values for DLCO, DLCO/VA, VA, vital capacity (VC), inspiratory vital capacity (IVC), and inspiratory capacity (IC) are suggested for clinical use to replace technically outdated reference values for clinical applications.

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 microm (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.

Comparison of methods for editing of ectopic beats in measurements of short-term non-linear heart rate dynamics.

Non-linear heart rate (HR) dynamics characterizes the fractal properties and complexity of the variations in HR. Ventricular and supraventricular ectopic beats might introduce a mathematical artefact to the analyses on sinus rhythm. We therefore evaluated the effects of different editing practices for ectopic beats such that 753 40-min ECG recordings were (i) not edited for the ectopic beats, or the ectopic beats were edited with (ii) an interpolation or with (iii) a deletion method before the analyses of non-linear HR dynamics. The non-linear HR dynamics analyses included detrended fluctuation analysis (DFA), approximate entropy, symbolic dynamics (SymDyn), fractal dimension and return map (RM). We found that the short-term scaling exponent (alpha1) of DFA, forbidden words of SymDyn and RM were sensitive measurements to the ectopic beats and there were strong correlations between these measurements and the number of ectopic beats. In addition, the unedited ectopic beats significantly lowered the stability of these measurements. However, the editing either with interpolation or deletion method corrected the measurements for the bias caused by the ectopic beats. On the contrary, the entropy measurements were not as sensitive to the ectopic beats. In conclusion, the ectopic beats affect the non-linear HR dynamics of sinus rhythm differently, causing a more marked bias in fractal than in complexity measurements of non-linear HR dynamics. This erroneous effect of ectopic beats can be corrected with a proper editing of these measurements. Therefore, there is an obvious need for standardized editing practices for ectopic beats before the analysis of non-linear HR dynamics.

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 diameter0.1 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 microg/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.

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) (1,000/cm(3)) of ultrafine particles (diameter 0.01-0.1 microm) 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 microg/m(3). During paced breathing, ultrafine particles, NO(2), 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/cm(3) 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.

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.

Personal, indoor, and outdoor exposures to PM2.5 and its components for groups of cardiovascular patients in Amsterdam and Helsinki.

The aim of the investigation was to assess the relations between pairs of personal, indoor, and outdoor levels of fine particles and their components with respect to effects for older subjects with cardiovascular disease. In the framework of a study funded by the European Union (Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air; referred to as ULTRA)*, panel studies were conducted in Amsterdam (The Netherlands) and Helsinki (Finland). Concentrations of outdoor particulate matter 2.5 pm or smaller in aerodynamic diameter (PM2.5) were measured at a fixed site in each location. With HEI funding, each subject's personal and indoor PM2.5 exposure was measured every other week for 6 months during the 24-hour period preceding intensive health measurements. Particle reflectance was measured as a marker for diesel exhaust. Elemental content of more than 50% of the personal and indoor samples and all corresponding outdoor samples was measured using x-ray fluorescence (XRF). Ion content (sulfate, nitrate) was measured using chromatography. For Amsterdam, 337 personal and 409 indoor measurements were collected from 37 subjects; for Helsinki, 336 personal and 503 indoor measurements were collected from 47 subjects. Median personal, indoor, and outdoor PM2.5 concentrations were 13.6, 13.6, and 16.5 microg/m3 in Amsterdam and 9.2, 9.2, and 11.1 microg/m3 in Helsinki. In both cities, personal and indoor PM2.5 concentrations were lower than and highly correlated with outdoor concentrations (median correlation coefficient [R] 0.7-0.8). For most elements, personal and indoor concentrations were also highly correlated with outdoor concentrations. The highest correlations (median R > 0.9) were found for sulfur (S), sulfate, and particle reflectance (reported as the absorption coefficient). Reflectance was a useful proxy for elemental carbon (EC), but site-specific calibration with EC data is necessary. The findings of this study support using fixed-site measurements as a measure of exposure to PM in time-series studies linking the day-to-day variations in PM to the day-to-day variations in health endpoints, especially for components of PM that are generally associated with fine particles and have few indoor sources.

Particulate air pollution is a matter of the heart.

Exposure to ambient particulate air pollution leads to adverse cardiovascular and respiratory effects. It has been estimated that air pollution could be responsible for 0.8 million (1.4%) deaths per year worldwide. Air pollution may worsen the sequelae of coronary atherosclerosis and, potentially accelerate its development. Some of the pollution effects occur rather abruptly, like the triggering of an arrhythmia or myocardial infarction, or some over time, such as, acceleration of the progression of atherosclerosis. Particulate matter is a complex mixture; the particles vary in size and composition. Therefore, it is unlikely that a single mechanism would explain the various effects seen. In this review, potential mechanisms of adverse cardiovascular effects of ambient air particles are discussed.

Theoretical analysis of the influence of aerosol size distribution and physical activity on particle deposition pattern in human lungs.

OBJECTIVES: A theoretical comparison of modeled particle depositions in the human respiratory tract was performed by taking into account different particle number and mass size distributions and physical activity in an urban environment. METHODS: Urban-air data on particulate concentrations in the size range 10 nm-10 microm were used to estimate the hourly average particle number and mass size distribution functions. The functions were then combined with the deposition probability functions obtained from a computerized ICRP 66 deposition model of the International Commission on Radiological Protection to calculate the numbers and masses of particles deposited in five regions of the respiratory tract of a male adult. The man's physical activity and minute ventilation during the day were taken into account in the calculations. RESULTS: Two different mass and number size distributions of aerosol particles with equal (computed) <10 microm particle mass concentrations gave clearly different deposition patterns in the central and peripheral regions of the human respiratory tract. The deposited particle numbers and masses were much higher during the day (0700-1900) than during the night (1900-0700) because an increase in physical activity and ventilation were temporally associated with highly increased traffic-derived particles in urban outdoor air. CONCLUSIONS: In future analyses of the short-term associations between particulate air pollution and health, it would not only be important to take into account the outdoor-to-indoor penetration of different particle sizes and human time-activity patterns, but also actual lung deposition patterns and physical activity in significant microenvironments.

Effects of particulate air pollution on blood pressure and heart rate in subjects with cardiovascular disease: a multicenter approach.

Given the hypothesis that air pollution is associated with elevated blood pressure and heart rate, the effect of daily concentrations of air pollution on blood pressure and heart rate was assessed in 131 adults with coronary heart disease in Helsinki, Finland; Erfurt, Germany; and Amsterdam, the Netherlands. Blood pressure was measured by a digital monitor, and heart rate was calculated as beats per minute from an electrocardiogram recording with the patient in supine position. Particle concentrations were measured at central measuring sites. Linear regression was used to model the association between 24-hr mean concentrations of particles and blood pressure and heart rate. Estimates were adjusted for trend, day of week, temperature, barometric pressure, relative humidity, and medication use. Pooled effect estimates showed a small significant decrease in diastolic and systolic blood pressure in association with particulate air pollution; a slight decrease in heart rate was found. Of the three centers, Erfurt revealed the most consistent particle effects. The results do not support findings from previous studies that had shown an increase in blood pressure and heart rate in healthy individuals in association with particles. However, particle effects might differ in cardiac patients because of medication intake and disease status, both affecting the autonomic control of the heart.

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.) 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.

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 microm (PM2.5) and the number concentrations of ultrafine particles (particle diameter 10 to 100 nm [NC(0.01-0.1)]) and accumulation mode particles (100 to 1000 nm [NC(0.1-1)]) 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 NC(0.1-1) 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 beta-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.