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National Particle Component Toxicity (NPACT) Initiative Report on Cardiovascular Effects

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National Particle Component Toxicity (NPACT) Initiative Report on Cardiovascular Effects RESEARCH REPORT HEAL TH HEAL TH National Particle Component EFFE CTS EFFE CTS Toxicity (NPACT) Initiative INSTITUTE INSTITUTE Report on Cardiovascular Effects 101 Federal Street, Suite 500 Sverre Vedal, Matthew J. Campen, Jacob D. McDonald, Boston, MA 02110, USA Number 178 October 2013 Joel D. Kaufman, Timothy V. Larson, Paul D. Sampson, +1-617-488-2300 Lianne Sheppard, Christopher D. Simpson, www.healtheffects.org and Adam A. Szpiro Section 1. NPACT Epidemiologic Study of Components RESEARCH of Fine Particulate Matter and Cardiovascular Disease in the MESA and WHI-OS Cohorts REPORT Sverre Vedal, Sun-Young Kim, Kristin A. Miller, Julie Richman Fox, Silas Bergen, Timothy Gould, Number 178 Joel D. Kaufman, Timothy V. Larson, Paul D. Sampson, October 2013 Lianne Sheppard, Christopher D. Simpson, and Adam A. Szpiro Section 2. NPACT Animal Toxicologic Study of Cardiovascular Effects of Mixed Vehicle Emissions Combined with Non-vehicular Particulate Matter Matthew J. Campen, Amie K. Lund, Steven K. Seilkop, and Jacob D. McDonald Section 3. Integrated Discussion Sverre Vedal and Matthew J. Campen Includes a Commentary by the Institute’s NPACT Review Panel National Particle Component Toxicity (NPACT) Initiative Report on Cardiovascular Effects Sverre Vedal, Matthew J. Campen, Jacob D. McDonald, Joel D. Kaufman, Timothy V. Larson, Paul D. Sampson, Lianne Sheppard, Christopher D. Simpson, and Adam A. Szpiro with a Commentary by the NPACT Review Panel Research Report 178 Health Effects Institute Boston, Massachusetts Trusted Science • Cleaner Air • Better Health Publishing history: This document was posted at www.healtheffects.org in October 2013. Citation for Research Report 178 in its entirety: Vedal S, Campen MJ, McDonald JD, Kaufman JD, Larson TV, Sampson PD, Sheppard L, Simpson CD, Szpiro AA. 2013. National Particle Component Toxicity (NPACT) Initiative Report on Cardiovascular Effects. Research Report 178. Health Effects Institute, Boston, MA. Citation for Section 1 only: Vedal S, Kim S-Y, Miller KA, Fox JR, Bergen S, Gould T, Kaufman JD, Larson TV, Sampson PD, Sheppard L, Simpson CD, Szpiro AA. 2013. Section 1. NPACT epidemiologic study of components of fi ne particulate matter and cardiovascular disease in the MESA and WHI-OS cohorts. In: National Particle Component Toxicity (NPACT) Initiative Report on Cardiovascular Effects. Research Report 178. Health Effects Institute, Boston, MA. Citation for Section 2 only: Campen MJ, Lund AK, Seilkop SK, McDonald JD. 2013. Section 2. NPACT animal toxicologic study of cardiovascular effects of mixed vehicle emissions combined with non-vehicular particulate matter. In: National Particle Component Toxicity (NPACT) Initiative Report on Cardiovascular Effects. Research Report 178. Health Effects Institute, Boston, MA. © 2013 Health Effects Institute, Boston, Mass., U.S.A. Asterisk Typographics, Barre, Vt., Compositor. Printed by Recycled Paper Printing, Boston, Mass. Library of Congress Catalog Number for the HEI Report Series: WA 754 R432. Cover paper: made with at least 55% recycled content, of which at least 30% is post-consumer waste; free of acid and elemental chlorine. Text paper: made with 100% post-consumer waste recycled content; acid free; no chlorine used in processing. The book is printed with soy-based inks and is of permanent archival quality. CONTENTS About HEI vii About This Report ix Contributors xi PREFACE: HEI’s Research Program on Particle Component Toxicity xiii HEI STATEMENT 1 INVESTIGATORS’ REPORT by Vedal et al. 5 OVERALL ABSTRACT 5 OVERALL INTRODUCTION 6 SECTION 1. NPACT Epidemiologic Study of Components of Fine Particulate Matter and Cardiovascular Disease in the MESA and WHI-OS Cohorts 9 ABSTRACT 9 OVERVIEW 10 SPECIFIC AIM 12 THE MESA ANALYSES 12 Introduction and Study Design 12 The MESA Cohort 12 MESA Exposure Data 13 Source Apportionment 24 Building and Validating the Spatiotemporal Exposure Model 43 Building and Validating the National Spatial Exposure Model 64 Secondary Estimates of Exposure 69 Analysis of Health Effects 69 THE WHI-OS ANALYSES 91 Introduction and Study Design 91 The WHI-OS Cohort 92 National Spatial Model Predictions 94 Secondary Exposure Estimates 96 Analysis of Health Effects 97 DISCUSSION 110 Main Health Effects Findings 110 Estimation of Exposure 111 Interpretation and Limitations of the Findings 115 CONCLUSIONS 119 ACKNOWLEDGMENTS 120 Research Report 178 REFERENCES 120 APPENDIX A: HEI Quality Assurance Statement 122 APPENDICES AVAILABLE ON THE WEB 123 ABOUT THE AUTHORS 123 Contributors 125 OTHER PUBLICATIONS RESULTING FROM THIS RESEARCH 126 ABBREVIATIONS AND OTHER TERMS 126 SECTION 2. NPACT Animal Toxicologic Study of Cardiovascular Effects of Mixed Vehicle Emissions Combined with Non-vehicular Particulate Matter 129 ABSTRACT 129 Background 129 Methods 129 Results 129 Conclusions 130 INTRODUCTION 130 SPECIFIC AIMS 132 METHODS AND STUDY DESIGN 132 Exposure Atmospheres 132 Biologic Endpoints 137 QUALITY ASSURANCE 140 RESULTS 140 Exposure Atmosphere Composition 140 Biologic Responses 144 Multiple Additive Regression Tree Analysis 154 DISCUSSION 160 IMPLICATIONS OF FINDINGS 164 ACKNOWLEDGMENTS 165 REFERENCES 165 APPENDICES AVAILABLE ON THE WEB 167 ABOUT THE AUTHORS 168 OTHER PUBLICATION RESULTING FROM THIS RESEARCH 168 ABBREVIATIONS AND OTHER TERMS 168 Research Report 178 SECTION 3. Integrated Discussion 171 INTEGRATING THE EPIDEMIOLOGIC AND TOXICOLOGIC STUDIES 171 TOXICOLOGIC AND EPIDEMIOLOGIC EXPOSURES 171 TOXICOLOGIC AND EPIDEMIOLOGIC ENDPOINTS 173 INTEGRATING EPIDEMIOLOGIC AND TOXICOLOGIC FINDINGS 173 Sulfate 174 Nitrate 175 Mixed Vehicular Engine Emissions 175 Road Dust and Crustal Sources 176 Organic Carbon 176 Sulfur Dioxide 176 SUMMARY AND SUGGESTIONS FOR IMPROVING INTEGRATION 176 REFERENCES 177 ABBREVIATIONS AND OTHER TERMS 178 COMMENTARY by the NPACT Review Panel 179 INTRODUCTION 179 SCIENTIFIC AND REGULATORY BACKGROUND 180 PM Characteristics, Components, and Sources 180 Epidemiologic Evidence 182 Toxicologic Evidence 183 Integrating Epidemiologic and Toxicologic Approaches in NPACT 184 Specifi c Aims 184 SECTION 1: EPIDEMIOLOGY STUDY 186 Introduction 186 Exposure Modeling for the MESA and WHI-OS Studies 186 Evaluation of the MESA and WHI-OS Exposure Assessment 188 Overview of the MESA Cohort Study 189 Key Results for the MESA Cohort 191 Evaluation of the MESA Cohort Study 193 WHI-OS Cohort Overview 195 Key Results from the WHI-OS Cohort 197 Evaluation of the WHI-OS Cohort Study 199 WHI-OS Study Conclusions 202 Research Report 178 SECTION 2: TOXICOLOGY STUDY 202 Specifi c Aims 202 Approach 202 Summary of Key Toxicologic Results 204 Evaluation of the Toxicology Study 207 OVERALL EVALUATION OF THE VEDAL REPORT 213 PM2.5 Components and Cardiovascular Outcomes in Humans 213 MVE and PM2.5 Components and Cardiovascular Outcomes in Mice 215 Summary and Conclusions for the Vedal Report 215 ACKNOWLEDGMENTS 216 REFERENCES 216 ABBREVIATIONS AND OTHER TERMS 221 SYNTHESIS OF THE NPACT INITIATIVE by the NPACT Review Panel 223 INTRODUCTION 223 INITIAL OBJECTIVES OF THE NPACT INITIATIVE 223 DATA AND STUDY DESIGN 224 PM Composition Data 224 Linking PM Components and Sources to Health Outcomes 225 Estimating Exposure Using Air Quality Data 226 Single-Pollutant and Multipollutant Models 227 Approaches to Animal Inhalation Exposures 227 COMPARING KEY FINDINGS ACROSS THE STUDIES 228 REFLECTIONS ON THE MAIN FINDINGS 231 ACKNOWLEDGMENTS 232 REFERENCES 232 ABBREVIATIONS AND OTHER TERMS 233 Related HEI Publications 235 HEI Board, Committees, and Staff 237 ABOUT HEI The Health Effects Institute is a nonprofi t corporation chartered in 1980 as an independent research organization to provide high-quality, impartial, and relevant science on the effects of air pollution on health. To accomplish its mission, the institute • Identifi es the highest-priority areas for health effects research; • Competitively funds and oversees research projects; • Provides intensive independent review of HEI-supported studies and related research; • Integrates HEI’s research results with those of other institutions into broader evaluations; and • Communicates the results of HEI’s research and analyses to public and private decision makers. HEI typically receives half of its core funds from the U.S. Environmental Protection Agency and half from the worldwide motor vehicle industry. Frequently, other public and private organizations in the United States and around the world also support major projects or research programs. For the research funded under the National Particle Component Toxicity initiative, HEI received additional funds from the American Forest & Paper Association, American Iron and Steel Institute, American Petroleum Institute, ExxonMobil, and Public Service Electric and Gas. HEI has funded more than 280 research projects in North America, Europe, Asia, and Latin America, the results of which have informed decisions regarding carbon monoxide, air toxics, nitrogen oxides, diesel exhaust, ozone, particulate matter, and other pollutants. These results have appeared in the peer-reviewed literature and in more than 200 comprehensive reports published by HEI. HEI’s independent Board of Directors consists of leaders in science and policy who are committed to fostering the public–private partnership that is central to the organization. The Health Research Committee solicits input from HEI sponsors and other stakeholders and works with scientifi c staff to develop a Five-Year Strategic Plan, select research projects for funding, and oversee their conduct. The Health Review Committee,
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