Sleep Apnea and STElevation Myocardial Infarction a Multidisciplinary Translational Study

? DESCRIPTION (provided by applicant): Sleep Apnea and ST-Elevation Myocardial Infarction: A Multidisciplinary Translational Study This proposal challenges conventional wisdom that sleep apnea only contributes to deleterious pro- inflammatory and pro-thrombotic events. Instead, sleep apnea may be a form of ischemic preconditioning- one of the most potent mechanisms to protect against myocardial ischemic injury. We hypothesize that a cardioprotective influence of intermittent hypoxia from sleep apnea leads to up-regulation of angiogenic factors, which in turn triggers the development of coronary collaterals and thereby protects the myocardium during a period of severe ischemia. Reduction of myocardial infarct size has been the key objective of research on ischemic myocardial disease over the past four decades. This study, if confirmatory of cardioprotection, will contribute to a paradigm shift. If the hypotheses are proven, the candidate will embark on future investigations to further explore the protective abilities of intermittent hypoxia in sleep apnea combined with individual gene analysis, which may provide new treatment strategies for cardiovascular diseases. The Aims of our study are: Aim 1. To determine an independent association between sleep apnea and myocardial injury in the early post-infarction period. Aim 2. To investigate mechanistic pathways of a cardioprotective role of sleep apnea in the early post- myocardial infarction period. This study addresses the gaps in the current literature on the association between sleep apnea and myocardial injury in the early post-infarction period. It includes: 1) Cardiac MRI to measure myocardial infarct size, microvascular obstruction, and myocardial viability during the early post-infarction period 2) Coronary collateral scoring using Rentrop score to measure the degree of collateral formation 3) Biomarkers of hypoxic stress including inflammatory and adaptive 4) Longitudinal assessment of sleep apnea with testing at two time points, one within days of myocardial infarction and second weeks after the event No research team to date has merged these components into one comprehensive study. Consequently, we do not have the information required to fully understand the aforementioned association. Therefore our study will provide an important novel, overarching assessment of the role of sleep apnea and myocardial injury. The candidate is currently an Assistant Professor of Medicine and Epidemiology/Population Health at Albert Einstein College of Medicine in New York. The candidate completed her clinical and research fellowship at Yale University School of Medicine and during that period she received a Master's in Chronic Disease Epidemiology at the Yale School of Public Health. During her fellowship, she received the Ruth L. Kirschstein National Research Service Award (Institutional Research Training Grant). The applicant is currently in the final year of a three-year intramural career development award (KL-2). In years one and two of this award, she measured plasma vascular endothelial growth factor levels in acute myocardial infarction patients (Shah, Sleep Breath 2012). This was the primary aim of the KL-2 award and the candidate reported the novel finding that vascular endothelial growth factor levels are higher in sleep apnea patients vs. non-sleep apnea patients with acute myocardial infarction (ATS 2013). Sleep apnea is a multicomponent disorder, however, with tissue-specific responses. During the KL-2 duration, the candidate recognized that a transdisciplinary approach is required to capture the complexity of sleep apnea's link with coronary atherosclerosis and related outcomes (infarct size). Therefore, during the KL-2 award period, the candidate broadened the scope of the project. She included sophisticated cardiac imaging techniques to accurately measure infarction characteristics, coronary collateral scoring and cardiac biomarkers. The candidate has successfully begun patient enrollment into this transdisciplinary pilot study. The candidate's long-term career goal i to succeed as a translational sleep investigator who can lead focused clinical trials and translational studies in sleep and cardiovascular diseases. Specifically, she plans to investigate how sleep apnea and its treatment impact myocardial infarction severity and recovery. The candidate has an exceptionally strong multidisciplinary mentoring team. With their guidance, she has outlined a career development plan that includes training in clinical cardiology, cardiovascular epidemiology, biomarker/translational research methodology, and cardiac imaging. It also includes formal coursework in advanced statistics, manuscript preparation and publication, participation in national and local meetings/conferences and preparing and submitting R01s. It is therefore clear that with NIH support, the candidate has every advantage to not only fill the gap in a potential transformative research question, but to also succeed in he career goal of becoming an independent investigator in the field of sleep medicine.