We performed a study of CO and CVD hospitalizations using data on >9.3 million Medicare enrollees in 126 U.S. urban counties over a 7-year period. Other recent time-series studies of CO and morbidity include a study of ten Canadian cities investigating congestive heart failure,5
and the two largest U.S.-based studies, which investigated congestive heart failure admissions in 7 communities10
and total CVD admissions in 8 communities.17
Mortality was examined in 19 European cities by the Air Pollution and Health: A European Approach (APHEA-2) investigators, finding independent associations of CO with total and CVD mortality.18
Ambient CO levels have also been associated with heart rate variability in a human exposure study of persons with coronary artery disease19
and other adverse health outcomes in multiple population-based studies, such as low birth weight20
and mortality.18, 21
Our results provide strong evidence of an association between outdoor CO concentrations and risk of CVD hospitalizations for an older population. The patterns of association by lag, with strongest effects on the same day, are consistent with CO kinetics and the likely mechanisms by which CO has adverse CVD effects. For the “control” category of injury, we found no evidence of an association, implying satisfactory adjustment for time-varying potential confounders.
Because the primary CO source in urban centers is traffic, we considered confounding by other traffic-related pollutants (NO2
, EC). With adjustment for these co-pollutants, the association remained although it was attenuated, particularly with NO2
adjustment. We cannot exclude the possibility that the observed associations could reflect pollution from traffic emissions generally, which have been associated with cardiovascular endpoints22, 23
and not from CO specifically. CO levels were moderately correlated with NO2
, also resulting from vehicle emissions among other sources.24
Our analyses estimate the effects of CO adjusted by other traffic-related pollutants. The total health impacts of air pollution from the traffic source, or from the air pollution mixture more broadly, are as yet unknown. Understanding the public health consequences of multiple pollutants is an area needing further research, as indicated by reports from the National Resource Council.25, 26
Because of the spatial distribution of ambient CO in urban areas, we anticipate potential misclassification of personal exposures for city-dwellers by our reliance on regulatory monitors. Extensive research has not been conducted on the relationship between personal exposure to CO and ambient measurements. Such work is needed, especially regarding which subpopulations (e.g., outdoor workers) may have differential exposure. A study of 56 subjects found little agreement between ambient and personal CO measurements.27
An examination of in-home CO distribution in Washington, DC found higher levels for those living in the metropolitan area than those in the suburbs.28
We did not find that the health effect estimates vary by the monitor coverage within a county although the results were suggestive of potential higher estimates with more dense monitor coverage. The exposure misclassification would tend to reduce estimates, implying that our results could underestimate risk of hospitalization associated with CO.
The present NAAQS for CO, promulgated in 1994, is based largely on results of studies involving exposure of volunteers with coronary heart disease to concentrations of CO sufficient to raise blood carboxyhemoglobin concentrations from the typical level of 1% in nonsmokers to as high as 6%.29, 30
The study participants had documented coronary heart disease, and study outcomes were clinically relevant indicators (increased arrhythmias,31, 32
time to ischemia or angina33, 34
). Effects on indicators of myocardial ischemia were identified at carboxyhemoglobin concentrations as low as 2%34
and for arrhythmias at 6%.31
The Coburn-Forster-Kane equation, which describes the relationship between inhaled CO and blood carboxyhemoglobin, was used by EPA to calculate ambient exposures that could result in carboxyhemoglobin concentrations associated with adverse effects, although the equation’s original aim was to estimate the rate of endogenous CO production.35
In another study, carboxyhemoglobin measurements did not correlate with clinical status in CO poisoning.36
Our results are consistent with clinical and animal model studies finding that CO exposure can adversely affect cardiac function.4, 37, 38
Many of these studies investigated high CO concentrations, often elevated by cigarette smoking, which far exceed the ambient levels studied here; and an early review of this literature noted that few studies explored low CO levels.37
One critical finding of our research is the perhaps unexpectedly strong effect observed at current ambient levels (). A 1 ppm increase in CO concentration, approximating the IQR across communities, would correspond to an approximate 0.1–0.2% increase in blood carboxyhemoglobin on average. The maximum changes in CO concentration within city, based on comparison of CO levels on adjacent days, are at a level that would be expected to increase carboxyhemoglobin by about 1%, sufficient to increase the level from the baseline of 1% typical of nonsmokers to the 2% value at which effects were observed in some exposure studies (). Additionally, clinical CO studies, which used volunteers and involved an exercise protocol, may have underestimated potential susceptibility of persons with coronary heart disease.
While physiological responses to CO have been well studied, much of the scientific evidence involves concentrations that are quite high in relation to current U.S. ambient levels. The acute and lethal toxicity of CO at high levels is well documented, and human exposure studies have shown acute CO poisoning at very high concentrations,2
although debate still exists regarding biological mechanisms of CO toxicity.39–41
Additional information on physiological mechanisms continues to be gained. CO exposure causes adverse health response through binding to hemoglobin and subsequent lessened delivery of oxygen, as hemoglobin’s affinity for CO is over 200 times that of oxygen.38
Other mechanisms have also been hypothesized including detriment to myoglobin function, generation of reactive oxygen species, and interruption of the terminal oxidase of the electron transport chain.40, 42–45
Recent in vitro and animal model studies indicate that low levels of CO may have therapeutic effects on tissue such as antioxidative and anti-inflammatory responses.46–49
This study provides one of the first population-based investigations of the health effects of current, low ambient CO levels. We provided evidence that the association between CO and risk of cardiovascular hospitalizations persists at levels of daily 1-hour maximum CO <1 ppm and that daily excursions of CO concentration occur that are sufficient to elevate carboxyhemoglobin to a level at which adverse effects have been observed experimentally. Most of the U.S. is in regulatory compliance with health-based CO regulations (35 ppm for the daily 1-hour maximum).11, 30
Higher levels of CO exist in some regions including areas with developing transportation networks, such as urban Chinese centers, where CO primarily results from traffic.50
While much of the current research on health and traffic-related air pollution focuses on particulate matter, our study indicates that ambient CO and traffic may present a far larger health burden than previously suspected.
With growing traffic in many urban centers, the health impacts of traffic-related air pollution are a current public health concern. This national study of 126 U.S. urban counties from 1999 to 2005 examines whether exposure to carbon monoxide (CO) on the same day and previous few days increases risk of cardiovascular (CVD) hospitalizations for an older population based on >9.3 million Medicare enrollees ≥65 years of age. Our findings indicate that higher levels of CO exposure are associated with an increased risk of CVD hospitalizations on the same day for multiple cause-specific CVD outcomes (ischemic heart disease, heart rhythm disturbances, heart failure, cerebrovascular disease, and total CVD admissions). Although it is not possible to fully disentangle the effects of CO and of other air pollutants produced by traffic, the association between CO and CVD hospital admissions remained after adjustment for other traffic-related pollutants: nitrogen dioxide (NO2); fine particulate matter (PM2.5) total mass; and Elemental Carbon PM2.5. The risk persisted even at low CO levels <1 ppm, which are well below the current U.S. health-based regulatory standard. This study provides one of the first population-based investigations of the health effects of current, low ambient CO levels and indicates that exposure to current CO levels may still pose a threat to public health, particularly for persons with CVD. It adds to other research showing that air pollution harms the health of people with CVD.