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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL079114-05
Application #
7923320
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M1))
Program Officer
Lewin, Daniel S
Project Start
2006-09-01
Project End
2011-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
5
Fiscal Year
2010
Total Cost
$106,596
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
May, Anna M; Gharibeh, Tarek; Wang, Lu et al. (2018) CPAP Adherence Predictors in a Randomized Trial of Moderate-to-Severe OSA Enriched With Women and Minorities. Chest 154:567-578
DeMartino, Theresanne; Ghoul, Rawad El; Wang, Lu et al. (2016) Oxidative Stress and Inflammation Differentially Elevated in Objective Versus Habitual Subjective Reduced Sleep Duration in Obstructive Sleep Apnea. Sleep 39:1361-9
Paz Y Mar, Hugo L; Hazen, Stanley L; Tracy, Russell P et al. (2016) Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial. Chest 150:80-90
Gharib, Sina A; Seiger, Ashley N; Hayes, Amanda L et al. (2014) Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes. Sleep 37:709-14
Seif, Fadi; Patel, Sanjay R; Walia, Harneet K et al. (2014) Obstructive sleep apnea and diurnal nondipping hemodynamic indices in patients at increased cardiovascular risk. J Hypertens 32:267-75
Seif, Fadi; Patel, Sanjay R; Walia, Harneet et al. (2013) Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden. J Sleep Res 22:443-51
Smith, J Gustav; Magnani, Jared W; Palmer, Cameron et al. (2011) Genome-wide association studies of the PR interval in African Americans. PLoS Genet 7:e1001304
Mehra, Reena; Xu, Fang; Babineau, Denise C et al. (2010) Sleep-disordered breathing and prothrombotic biomarkers: cross-sectional results of the Cleveland Family Study. Am J Respir Crit Care Med 182:826-33
Marcus, Gregory M; Alonso, Alvaro; Peralta, Carmen A et al. (2010) European ancestry as a risk factor for atrial fibrillation in African Americans. Circulation 122:2009-15
Mehra, Reena; Stone, Katie L; Varosy, Paul D et al. (2009) Nocturnal Arrhythmias across a spectrum of obstructive and central sleep-disordered breathing in older men: outcomes of sleep disorders in older men (MrOS sleep) study. Arch Intern Med 169:1147-55

Showing the most recent 10 out of 16 publications