Asthma and Atherosclerosis Public
Onufrak, Stephen (2007)
Published
Abstract
Asthma and atherosclerosis are clinically different diseases that share a common biological mechanism: inflammation. Thus, it is plausible that alterations in systemic inflammatory response among asthmatics could result in increased inflammation in the artery wall and predispose them to atherosclerosis. Asthma has also been associated with atherosclerotic disease in several studies, with some suggestion that the asthma-atherosclerosis association may be limited to or stronger among women. Although asthma-related inflammation is a biologically plausible mechanism of the observed association with atherosclerotic disease, no studies to date have examined this possibility. Furthermore, previous research in this area has generally ignored the increasingly accepted notion that asthma is not a single disease but a syndrome overlying a number of heterogeneous disease subtypes. Three studies were performed for this dissertation. The first study assessed the cross-sectional association of asthma with coronary artery disease (CAD) among patients undergoing cardiac catheterization at Emory University Hospital and further examined whether haplotypes of genes that regulate leukotriene production were differentially associated with CAD according to asthma status and gender. Analysis indicated that although asthma was negatively associated with CAD in this highly-selected population, the association of ALOX5AP haplotypes with CAD was significantly modified by asthma status and gender whereby a positive association with CAD was observed only among asthmatic women. The second and third studies of the dissertation utilized data from the Atherosclerosis Risk in Communities (ARIC) study and examined the association of the asthma age of onset subtypes with incident CAD, incident stroke, and carotid intima medial thickness, an indicator of subclinical atherosclerosis. The results of these studies suggest that adult onset asthma, but not child onset asthma, is associated with atherosclerotic disease, and that this association occurs only among women. Taken together, the results of this dissertation suggest that asthma is associated with atherosclerotic disease among women but not men and that this association differs according to asthma subtype. In addition, our results support the role of leukotriene-mediated inflammation as a biologic mechanism underlying the asthma-atherosclerosis association.
Table of Contents
1 INTRODUCTION Brief Overview Research Purpose Scope of Dissertation Study Responsibilities Human Subjects Protection 2 LITERATURE REVIEW Background on Atherosclerosis and Atherosclerotic Disease Outcomes Diagnosis and Measurement of Atherosclerotic Disease Genetic Background and Genetic Association Studies Atherosclerosis and Leukotrienes Background on Asthma Asthma and Leukotrienes Previous Studies of The Association of Asthma and Atherosclerosis Rationale and Significance of the Proposed Studies Primary Research Hypotheses 3 METHODOLOGY Overview of Dissertation Projects Project One Overview Patient Protection and Confidentiality Procedures Population and Exclusions Data Collection Procedures Role of Candidate in Data Collection Data Collection Variables Genetic Methods Statistical Procedures Power and Sample Size Strengths and Limitations Projects Two and Three Overview Patient Protection and Confidentiality Procedures Population and Exclusions Data Collection Procedures Data Collection Variables Statistical Procedures Power and Sample Size Strengths and Limitations 4 ASTHMA AS A RISK FACTOR FOR CORONARY ARTERY DISEASE AMONG SUBJECTS UNDERGOING CORONARY CATHETERIZATION Abstract Introduction Methods Results Discussion References 5 ADULT-ONSET ASTHMA IS ASSOCIATED WITH INCIDENT CORONARY HEART DISEASE AND STROKE AMONG WOMEN Abstract Introduction Methods Results Discussion References 6 ADULT-ONSET ASTHMA IS ASSOCIATED WITH INCREASED CAROTID ATHEROSCLEROSIS AMONG WOMEN IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY Abstract Introduction Methods Results Discussion References 7 Conclusions 8 SELECTED BIBLIOGRAPHY Appendix A Emory Internal Review Board (IRB) Approval Letter for Project One B Emory IRB Approval Letter for Projects Two And Three C Study Questionnaire for Catheterization Study
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