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Study Links Same-Day CO to Risk of Hospitalization for CVD

By Dixie Ann Sawin
October 2009

Michelle Bell, Ph.D.
"We found a positive and statistically significant association between same-day carbon monoxide levels and an increased risk of hospitalization for cardiovascular disease in general, as well as for multiple, specific cardiovascular disease outcomes," Bell explained. (Photo courtesy of Michelle Bell
and Yale University)

Jonathan Samet, M.D.
Before moving to the University of Southern California last year, Samet was a professor and chairman of the Department of Epidemiology at Johns Hopkins, where Bell received her doctorate and collaborated on previous studies with Samet, Peng and Dominici.
(Photo courtesy of Jonathan Samet)

An NIEHS- and U.S. Environmental Protection Agency (EPA)-funded epidemiological study published in the September 2009 issue of Circulation presents strong evidence of an association between daily low-level carbon monoxide (CO) exposure and an increased risk of same-day hospitalization for cardiovascular disease (CVD) among an older population. Associate Professor Michelle Bell, Ph.D., of the Yale School of Forestry and Environmental Studies and a recipient of the NIEHS Outstanding New Environmental Scientist (ONES) Award, was lead author and principal investigator on the multi-site, time-series study.

Bell ( NIEHS and her colleagues analyzed a cohort of 9.3 million Medicare enrollees, aged 65 and over, in one of the first national-scale, population-based investigations of the health effects of low ambient CO levels. The study ( NIEHS assessed subjects from 126 urban counties in 41 states across the U.S. over a seven-year period from 1999 to 2005. The findings underscore the importance of re-evaluating daily exposure limits, relative to air pollution components such as CO and particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5).

According to the study's authors, the primary source of CO in urban centers is traffic exhaust. Although the mechanism involved remains unclear, CO is known to bind hemoglobin - forming carboxyhemoglobin, which decreases its affinity for oxygen and affects vital downstream cellular processes implicated in such outcomes as ischemic heart disease, heart rhythm disturbances, heart failure and cerebrovascular disease.

The most compelling laboratory evidence of an association between CO and CVDs has come from controlled exposure studies on CO inhalation at levels that simulate the urban environment. However, the findings from these studies and previous epidemiological studies have been inconclusive.

In their seminal study, Bell and her co-authors provide much needed information. They report that the current outdoor CO level for an average 1-hour daily maximum exposure was 1.6 ppm in most counties included in the study - significantly below the health-based National Ambient Air Quality Standard of 35 ppm set by the U.S. EPA in 1994. This regulatory threshold was based largely on studies of volunteers with coronary artery disease who were exposed to CO concentrations capable of raising their blood carboxyhemoglobin from the typical non-smoker (basal) level of one to six percent.

The researchers found that the CO levels currently present in ambient air were associated with increased risk of cardiovascular hospitalizations in an older population, and this association persisted even at very low CO levels. The authors note that it is difficult to disentangle the health effects of CO from other traffic-related pollutants. Interestingly, they also found that the association retained statistical significance, although the effect estimate was attenuated, when they adjusted for possible confounding effects of other traffic-related pollutants, such as nitrogen dioxide, PM2.5 and elemental carbon.

A limiting factor of their study, the authors acknowledge, is a possible misclassification of the personal exposure of city dwellers because of the study's reliance on stationary outdoor monitors. This misclassification could lead to reduced estimates, possibly underestimating the risk of CVD hospitalization associated with CO exposure. "Understanding the public health consequences of multiple pollutants is an area needing further research," the researchers emphasize in their discussion.

Bell receives support from an NIEHS grant for "National Assessment of the Mortality and Morbidity Effects of Tropospheric Ozone." Co-author Jonathan Samet, M.D. ( NIEHS , of the Keck School of Medicine at the University of Southern California, is renowned for his work on the effects of particulate matter on health, in particular the roles of air pollution, ozone and smoking in lung cancer epidemiology. The two other co-authors, biostatisticians Roger D. Peng, Ph.D., of Johns Hopkins University Bloomberg School of Public Health, and Francesca Dominici, Ph.D. ( NIEHS , of Harvard University School of Public Health, provided critical analytical support for the data-rich study.

Citation: Bell ML, Peng RD, Dominici F, Samet JM. ( NIEHS 2009. Emergency hospital admissions for cardiovascular diseases and ambient levels of carbon monoxide: results for 126 United States urban counties, 1999-2005. Circulation 120(11):949-955. Epub ahead of print.

Extramural Papers of the Month summary(

(Dixie-Ann Sawin, Ph.D., is a post-doctoral research fellow in the NIEHS Laboratory of Neurobiology Neurotoxicology Group on detail as a writer for the Environmental Factor.)

Is Air Conditioning an Answer for Modifying the Effects of Air Pollution?

In a brief report ( NIEHS appearing in the September 2009 issue of Epidemiology, Bell and her colleagues present findings that air conditioning (AC) significantly attenuated the effects of PM2.5 on the health of 65-year-olds from 168 US counties, assessed from 1999-2005. This study was based on their earlier finding that risk of hospitalization for CVD or urgent respiratory illness differed by community. There, they assessed whether the between-community effect was due to AC prevalence, that is, the fraction of households with AC. In summary, they showed that AC prevalence lowered the short-term effects of PM2.5 on CVD hospitalizations.

Although similar findings have been suggested by others, this study was the first to confirm that the presence of central AC, as opposed to solitary units, can significantly impact individual health by filtering outdoor allergens, preventing them from entering indoor areas. However, the researchers acknowledged that this association might be lessened by a number of factors including inadequate maintenance of AC systems. The increasing numbers of households with central AC, coupled with increased energy use by these systems, could also subsequently contribute to greenhouse gas emission and decreased overall health. Thus, they emphasized that future research on the overall health benefit of AC on PM-related health issues should incorporate climate change considerations.

Citation: Bell ML, Ebisu K, Peng RD, Dominici F. ( NIEHS 2009. Adverse health effects of particulate air pollution: modification by air conditioning. Epidemiology 20(5):682-686.

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