In the December 1952 smog disaster in London, a substantial increase in mortality was closely associated with the increase in air pollution. Deaths from cardiovascular causes were elevated as well as respiratory deaths. The increase was greatest in the elderly. Hospital admissions were increased for both respiratory and cardiovascular diseases. Since then, many studies have reported associations between lower concentrations of air pollution and daily mortality. Little attention has been paid to the question of hospital admissions for cardiovascular illness, however. This study examined the association between air pollution and cardiovascular hospital admissions for persons aged 65 years and older in the Detroit, Michigan, metropolitan area during the years 1986-1989. After controlling for seasonal and other long-term temporal trends, temperature, and dew point temperature, the particulate matter with an aerodiameter of < or = 10 microns (PM10) was associated with daily admissions for ischemic heart disease (relative risk (RR) = 1.018, 95% confidence interval (CI) 1.005-1.032 for an interquartile range (32 micrograms/m3) increase in pollution). SO2, CO, and ozone made no independent contribution to ischemic heart disease admissions. Both PM10 (RR = 1.024, 95% CI 1.004-1.044) and CO (RR = 1.022, 95% CI 1.010-1.034 for an interquartile range (1.28 ppm) increase in pollution) showed independent associations with heart failure admissions. These results were robust to alternate methods of estimation and weather control.

Air Pollution and Hospital Admissions for Cardiovascular Disease in Detroit, Michigan

This study examines the consistency of the association between particulate matter less than 10 microm in aerodynamic diameter (PM10), carbon monoxide (CO), and hospital admissions for cardiovascular disease across eight urban counties with different levels of correlation between pollutants and between the pollutants and weather. I fit Poisson regression models controlling for day-of-week effects and using nonparametric smoothing to control for season and weather. Daily variation in PM10 was associated with hospital admissions for heart disease in the elderly (2.48% increase, for an interquartile range increase in exposure; 95% confidence limits = 1.82%, 3.15%). Daily variation in CO was also associated with admissions (2.79% increase, for an interquartile range (1.75 parts per million) increase in exposure; 95% confidence limits = 1.89%, 3.68%). These associations held in both humid and dry locations and were independent of the correlation between the pollutants and weather or other pollutants. The effect size estimates for PM10 and CO likewise showed no association with their correlation in each location, as one would expect if one pollutant were merely a proxy for the other. The PM10 effects are consistent with recent animal data showing cardiovascular effects and with preliminary human data showing effects on heart rate variability and plasma viscosity. The CO results are consistent with literature on angina exacerbations.

Air pollution and hospital admissions for heart disease in eight U.S. counties.

The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies designed for the local production of angiogenic growth factors in patients who are not candidates for conventional revascularization. The results of recent clinical trials of proangiogenesis gene therapy have been disappointing; however, significant limitations in experimental design, in particular in gene transfer strategies, preclude drawing definitive conclusions. In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor (AdVEGF121, 4 x 10(10) particle units (p.u.)). Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were randomized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment. Exercise time to 1 mm ST-segment depression, the predefined primary end-point analysis, was significantly increased in the AdVEGF121 group compared to control at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks < or =0.001). However, if anything the results of nuclear perfusion imaging favored the control group, although the AdVEGF121 group achieved higher workloads. Overall there was no significant difference in adverse events between the two groups, despite the fact that procedure-related events were seen only in the thoracotomy group. Therefore, administration of AdVEGF121 by direct intramyocardial injections resulted in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease.

Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment.

OBJECTIVES. Preexisting data sets were used to investigate the association between hospital admissions for congestive heart failure and air pollutants. METHODS. Medicare hospital admissions data, ambient air pollution monitoring data, and meteorological data were used to create daily values of hospital admissions for congestive heart failure, maximum hourly temperature, and maximum hourly levels of carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone. Data were compiled for each of seven cities (Chicago, Detroit, Houston, Los Angeles, Milwaukee, New York, and Philadelphia) for 1986 through 1989. Single-pollutant and multipollutant models with adjustments for temperature, seasonal effects, and weekly cycles were used in conducting negative binomial regression analyses. RESULTS. Ambient carbon monoxide levels were positively associated with hospital admissions for congestive heart failure in the single-pollutant and multipollutant models for each of the seven cities. The relative risk of hospital ad...

Ambient air pollution and hospitalization for congestive heart failure among elderly people in seven large US cities.

We examined the role that ambient air pollution plays in exacerbating cardiac disease by relating daily fluctuations in admissions to 134 hospitals for congestive heart failure in the elderly to daily variations in ambient concentrations of carbon monoxide, nitrogen dioxide, sulfur dioxide, ozone, a

Association between ambient carbon monoxide levels and hospitalizations for congestive heart failure in the elderly in 10 Canadian cities

The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.

Ronald H. Selvester

Papers

Effects of carbon monoxide on myocardial ischemia.