Final Report: Carbon Monoxide and Atherosclerosis

EPA Grant Number: R828112C057
Subproject: this is subproject number 057 , established and managed by the Center Director under grant R828112
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Health Effects Institute (2000 — 2005)
Center Director: Greenbaum, Daniel S.
Title: Carbon Monoxide and Atherosclerosis
Investigators: Penn, Arthur
Institution: New York University Medical Center
EPA Project Officer: Hunt, Sherri
Project Period: April 1, 2000 through March 31, 2005
RFA: Health Effects Institute (1996) RFA Text |  Recipients Lists
Research Category: Air , Health Effects

Objective:

Carbon monoxide is a ubiquitous air pollutant. It is found in cigarette smoke and emissions from motor vehicles, industrial processes, and poorly ventilated combustion sources. Despite reductions in ambient carbon monoxide concentrations during the last decade, 22 million people live in areas of the United States that exceed the National Ambient Air Quality Standard for carbon monoxide (9 parts per million [ppm] averaged over eight hours and 35 ppm averaged over one hour). Inhaling carbon monoxide is dangerous because the gas binds to hemoglobin in red blood cells to form carboxyhemoglobin. This displaces oxygen and reduces hemoglobin's ability to deliver oxygen to body tissues. If tissues are deprived of oxygen, transient or permanent damage can occur, especially in those organs that demand high oxygen delivery, such as the brain and heart. The lethal consequences of exposure to high concentrations of carbon monoxide are well known. There is also concern that exposure to low levels of carbon monoxide may produce adverse effects, especially on the cardiovascular system.

Carbon monoxide could manifest its toxic effects on the heart and blood vessels in two ways, either by causing acute, short-term effects on oxygen delivery or by contributing to the development of cardiovascular diseases such as atherosclerosis. Atherosclerosis is a progressive disease characterized by thickening of the arteries and a buildup of deposits of fat, cholesterol, cells, and connective tissue in the inner lining of the blood vessels. These deposits, called plaques, can partially or totally block the flow of blood through the artery. The known risk factors for atherosclerosis are family history of the disease, diet, high blood pressure, and cigarette smoking. (Mainstream and sidestream cigarette smoke have extremely high levels of carbon monoxide [400 to 1,000 ppm]). It is important to know whether chronic exposure to ambient levels of carbon monoxide is also a risk factor for developing atherosclerosis because this disease is the leading contributor to deaths by heart attack and stroke in the United States.

Summary/Accomplishments (Outputs/Outcomes):

Birds are appropriate animal models for studying atherosclerosis because some species develop spontaneous atherosclerotic plaques that resemble those in humans. Dr. Arthur Penn and his colleagues previously had shown that the development of atherosclerotic plaques in cockerels (young roosters) was enhanced when the birds were exposed to cigarette smoke or treated with agents that stimulate cell proliferation, such as chemical carcinogens. In the study described here, Dr. Penn exposed cockerels to either air or defined levels of carbon monoxide (50 to 200 ppm) for 16 weeks and measured the size of the atherosclerotic plaques in the abdominal aorta. He also examined whether carbon monoxide promoted atherosclerosis when the birds were fed a low cholesterol (0.1%) diet and exposed to carbon monoxide (100 ppm) at the same time. Finally, he determined whether carbon monoxide exposure altered the development of preexisting plaques.

In this study, none of the carbon monoxide exposures, either alone, or in combination with a low cholesterol diet, had an effect on the rate of development or the regression of atherosclerotic plaques in cockerels. Reliable blood carboxyhemoglobin measurements were not obtained. Consequently, there was no biomarker linking external carbon monoxide exposure concentrations and external dose. Because birds and mammals differ in their uptake and elimination of carbon monoxide, it is possible that the actual carbon monoxide body burden was relatively minimal and not comparable to human exposures. Considering this uncertainty, the results of this study do not provide a definitive answer to the question of whether exposure to carbon monoxide is a risk factor for atherosclerosis. The evidence favoring such a role at ambient carbon monoxide levels is not strong; however, because of the importance of the problem, the issue warrants further evaluation.

Supplemental Keywords:

Air, particulate matter, air toxics, mobile sources, epidemiology, animal model, health effects, ambient air quality, indoor air quality, second hand smoke, carbon monoxide, biomarkers., RFA, Health, Scientific Discipline, Air, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, mobile sources, Biochemistry, Disease & Cumulative Effects, indoor air, ambient air quality, lung injury, particulates, motor vehicles, air pollutants, exposure and effects, indoor exposure, human health effects, inhalability, lung, second hand smoke, engines, epidemelogy, ambient air, airway disease, atherosclerosis, air pollution, emissions, environmental health effects, cigarette smaoke, automobiles, carbon monoxide, human exposure, inhalation, ambient particle health effects, lung inflammation, particulate exposure, coronary artery disease, cigarette smoke, inhalation toxicology, inhaled, ambient particulates, environmental toxicant, harmful environmental agents, human health, indoor air quality, environmental tobacco smoke, cardiovascular disease, human health risk, air quality

Progress and Final Reports:

Original Abstract
  • 2000
  • 2001
  • 2002
  • 2003

  • Main Center Abstract and Reports:

    R828112    Health Effects Institute (2000 — 2005)

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R828112C042 Does Inhalation of Methanol Vapor Affect Human Neurobehavior?
    R828112C043 Human Responses to Nitrogen Dioxide
    R828112C044 The Role of Inflammation in Ozone-Induced Lung Injury
    R828112C045 How Does Exercise Affect the Dose of Inhaled Air Pollutants?
    R828112C046 How Do Chemicals in Diesel Engine Exhaust Damage DNA?
    R828112C047 Effect of Nitrogen Dioxide on Bacterial Respiratory infection in Mice
    R828112C048 Effects of Ozone Exposure on Airway Epithelium
    R828112C049 Inhalation of Aldehydes and Effects on Breathing
    R828112C050 Does Ozone Cause Precancerous Changes in Cells?
    R828112C051 Effects of Formaldehyde on Human Airway Epithelial Cells Exposed in a Novel Culture System
    R828112C052 Carbon Monoxide and Cardiac Arrhythmias
    R828112C053 Effects of Formaldehyde and Particle-Bound Formaldehyde on Lung Macrophage Functions
    R828112C054 Mechanisms for Protecting Lung Epithelial Cells Against Oxidant Injury
    R828112C055 Relationship of Nitropyrene-Derived DNA Adducts to Carcinogenesis
    R828112C056 Particle Trap Effects on Heavy-Duty Diesel Engine Emissions
    R828112C057 Carbon Monoxide and Atherosclerosis
    R828112C058 Nitrogen Dioxide and Respiratory Illness in Children
    R828112C059 Noninvasive Methods for Measuring Ventilation in Mobile Subjects
    R828112C060 Oxidant Air Pollutants and Lung Cancer: An Animal Model
    R828112C061 Detection of Carcinogen-DNA Adducts: Development of New Methods
    R828112C062 Effects of Carbon Monoxide on Heart Muscle Cells
    R828112C063 Development of Personal Ozone Samplers: Three Approaches
    R828112C064 Development of Biomarkers to Monitor Carcinogen Exposure
    R828112C065 Effects of Prolonged Ozone Inhalation on Collagen Structure and Content in Rat Lungs
    R828112C065II Prolonged Ozone Exposure and the Contractile Properties of Isolated Rat Airways
    R828112C065III Changes in Complex Carbohydrate Content and Structure in Rat Lungs Caused by Prolonged Ozone Inhalation
    R828112C065IV Genetic Control of Connective Tissue Protein Synthesis After Prolonged Ozone Inhalation
    R828112C065V Pulmonary Function Alterations in Rats After Chronic Ozone Inhalation
    R828112C065VII Prolonged Ozone Exposure Leads to Functional and Structural Changes in the Rat Nose
    R828112C065VIII - IX Studies of Changes in Lung Structure and Enzyme Activities in Rats After Prolonged Exposure to Ozone
    R828112C065X An Innovative Approach to Analyzing Multiple Experimental Outcomes: A Case Study of Rats Exposed to Ozone
    R828112C065XI The Consequences of Prolonged Inhalation of Ozone on Rats: An Integrative Summary of the Results of Eight Collaborative Studies
    R828112C066 Interactive Effects of Nitropyrenes in Diesel Exhaust
    R828112C067 Detection of Formaldehyde–DNA Adducts: Development of New Methods
    R828112C068I Comparison of the Carcinogenicity of Diesel Exhaust and Carbon Black in Rat Lungs
    R828112C068II An Investigation of DNA Damage in the Lungs of Rats Exposed to Diesel Exhaust
    R828112C068III No Evidence For Genetic Mutations Found In Lung Tumors From Rats Exposed To Diesel Exhaust or Carbon Black
    R828112C069 Noninvasive Determination of Respiratory Ozone Absorption: The Bolus-Response Method
    R828112C070 The Effects of Inhaled Oxidants and Acid Aerosols on Pulmonary Function
    R828112C071 Biochemical Consequences of Ozone Reacting with Membrane Fatty Acids
    R828112C072 DNA Mutations in Rats Treated with a Carcinogen Present in Diesel Exhaust
    R828112C073 Developmental Neurotoxicity of Inhaled Methanol in Rats
    R828112C074 Methanol Distribution in Non Pregnant and Pregnant Rodents
    R828112C075 Is Increased Mortality Associated with Ozone Exposure in Mexico City?
    R828112C076 Effects of Fuel Modification and Emission Control Devices on Heavy-Duty Diesel Engine Emissions
    R828112C077 Metabolic Studies in Monkeys Exposed to Methanol Vapors
    R828112C078 Effects of Ozone on Pulmonary Function and Airway Inflammation in Normal and Potentially Sensitive Human Subjects
    R828112C079 Improvement of a Respiratory Ozone Analyzer
    R828112C080 Mechanism of Oxidative Stress from Low Levels of Carbon Monoxide
    R828112C081 Long-Term Exposure to Ozone: Development of Methods to Estimate Past Exposures and Health Outcomes
    R828112C082 Effects of Ambient Ozone on Healthy, Wheezy, and Asthmatic Children
    R828112C083 Daily Changes in Oxygen Saturation and Pulse Rate Associated with Particulate Air Pollution and Barometric Pressure
    R828112C084 Evaluation of The Potential Health Effects of the Atmospheric Reaction Products of Polycyclic Aromatic Hydrocarbons
    R828112C085 Mechanisms of Response to Ozone Exposure: The Role of Mast Cells in Mice
    R828112C086 Statistical Methods for Epidemiologic Studies of the Health Effects of Air Pollution
    R828112C087 Development of New Methods to Measure Benzene Biomarkers
    R828112C088 Alveolar Changes in Rat Lungs After Long-Term Exposure to Nitric Oxide
    R828112C089 Effects of Prenatal Exposure to Inhaled Methanol on Nonhuman Primates and Their Infant Offspring
    R828112C090 A Pilot Study of Potential Biomarkers of Ozone Exposure
    R828112C091 Effects of Concentrated Ambient Particles on the Cardiac and Pulmonary Systems of Dogs
    R828112C092 Cancer, Mutations, and Adducts in Rats and Mice Exposed to Butadiene and Its Metabolites
    R828112C093 Effects of Concentrated Ambient Particles in Rats and Hamsters: An Exploratory Study
    R828112C094I The National Morbidity, Mortality, and Air Pollution Study: Methods and Methodologic Issues
    R828112C094II The National Morbidity, Mortality, and Air Pollution Study: Morbidity and Mortality from Air Pollution in the United States
    R828112C095 Association of Particulate Matter Components with Daily Mortality and Morbidity in Urban Populations
    R828112C096 Acute Pulmonary Effects of Ultrafine Particles in Rats and Mice
    R828112C097 Identifying Subgroups of the General Population That May Be Susceptible to Short-Term Increases in Particulate Air Pollution
    R828112C098 Daily Mortality and Fine and Ultrafine Particles in Erfurt, Germany
    R828112C099 A Case-Crossover Analysis of Fine Particulate Matter Air Pollution and Out-of-Hospital Sudden Cardiac Arrest
    R828112C100 Effects of Mexico City Air on Rat Nose
    R828112C101 Penetration of Lung Lining and Clearance of Particles Containing Benzo[a]pyrene
    R828112C102 Metabolism of Ether Oxygenates Added to Gasoline
    R828112C103 Characterization and Mechanisms of Chromosomal Alterations Induced by Benzene in Mice and Humans
    R828112C104 Acute Cardiovascular Effects in Rats from Exposure to Urban Ambient Particles
    R828112C105 Genetic Differences in Induction of Acute Lung Injury and Inflammation in Mice
    R828112C106 Effects on Mice of Exposure to Ozone and Ambient Particle Pollution
    R828112C107 Emissions from Diesel and Gasoline Engines Measured in Highway Tunnels
    R828112C108 Case-Cohort Study of Styrene Exposure and Ischemic Heart Disease Investigators
    R828112C110 Effects of Metals Bound to Particulate Matter on Human Lung Epithelial Cells
    R828112C111 Effect of Concentrated Ambient Particulate Matter on Blood Coagulation Parameters in Rats
    R828112C112 Health Effects of Acute Exposure to Air Pollution
    R828112C113 Benzene Metabolism in Rodents at Doses Relevant to Human Exposure from Urban Air
    R828112C114 A Personal Particle Speciation Sampler
    R828112C115 Validation and Evaluation of Biomarkers in Workers Exposed to Benzene in China
    R828112C116 Biomarkers in Czech Workers Exposed to 1,3-Butadiene: A Transitional Epidemiologic Study
    R828112C117 Peroxides and Macrophages in the Toxicity of Fine Particulate Matter in Rats
    R828112C118 Controlled Exposures of Healthy and Asthmatic Volunteers to Concentrated Ambient Particles in Metropolitan Los Angeles
    R828112C119 Manganese Toxicokinetics at the Blood-Brain Barrier
    R828112C120 Effects of Exposure to Concentrated Ambient Particles from Detroit Air on Healthy Rats and Rats with Features of Asthma or Mild Bronchitis
    R828112C121 Field Evaluation of Nanofilm Detectors for Measuring Acidic Particles in Indoor and Outdoor Air
    R828112C123 Time-Series Analysis of Air Pollution and Mortality: A Statistical Review
    R828112C126 Effects of Exposure to Ultrafine Carbon Particles in Healthy Subjects and Subjects with Asthma
    R828112C128 Neurogenic Responses of Rat Lung to Diesel Exhaust
    R828112C130-I Relationships of Indoor, Outdoor, and Personal Air (RIOPA). Part I. Collection Methods and Descriptive Analyses
    R828112C132 An Updated Study of Mortality Among North American Synthetic Rubber Industry Workers