Oxidative Stress in Sleep Apnea and Cardiac Disease

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DESCRIPTION (provided by applicant): I am an Assistant Professor of Medicine in the Divisions of Pulmonary/Critical Care/Sleep Medicine and Epidemiology/Biostatistics, and a recent graduate of Clinical Research Scholars Program, which awards a Master of Science in Clinical Research degree. My goals are to develop independent research aimed to answer fundamental questions regarding cardiovascular disease (CVD) outcomes of sleep disordered breathing (SDB). I am interested in blending epidemiological and translational approaches to identify individuals at highest risk for developing SDB-related CVD, and to clarify underlying disease mechanisms. This award will further expand research skills, providing an intense hands-on training experience aimed at: 1.) Honing skills in conducting rigorous randomized controlled studies and analyzing large epidemiological datasets, 2.) Gaining new skills in relevant translational research related to utilizing state-of-the-art bioassays, and 3.) Understanding how to optimally incorporate non-invasive cardiac function tests in epidemiological studies; with immediate applications to the proposed research. The objective of this proposal is the rigorous systematic assessment of the role of oxidative stress as a primary culprit in the pathophysiologic pathway linking SDB and CVD. First, a cross sectional analysis will be performed using existing blood and urine specimens collected on a large cohort, assessing between individual differences in oxidative stress markers from carefully chosen general and specific pathways to assess relationships between indices of SDB and oxidative stress. This will also allow me to hone writing/ analytic skills and inform future analyses. Secondly, I have designed an independent randomized, controlled, parallel design trial assessing the impact of SDB treatment (i.e. reversal of hypoxemia, etc.) on levels of oxidative stress markers. Also, secondary treatment effects on endothelial dysfunction (evaluated by brachial ultrasound), inflammation, insulin resistance and blood pressure will be assessed, including an evaluation of how observed treatment effects may be mediated by levels of oxidative stress. A logistically feasible five-year training program is proposed with a team of faculty mentors from strong research departments. This proposal addresses important knowledge gaps regarding the physiologic basis of the SDB-CVD relationship. Clarification of the role of oxidative stress will allow for use as potential stratification and prediction of CVD outcomes in individuals with SDB. The proposal will provide a key training opportunity to foster my development as an independent clinical epidemiologist with commitment to patient-based research in sleep medicine and cardiopulmonary disease.