Targeted Treatment of Obstructive Sleep Apnea to Reduce Cardiovascular Disparity

描述（由申请人提供）： 该临床科学研究与发展职业发展奖（CDA 2）的候选人是Bharati Prasad，MD，MS，Jesse Brown VAMC的肺部，重症监护和睡眠医学工作人员医生。普拉萨德博士的学术任命是作为一个终身助理教授在伊利诺伊大学芝加哥（UIC）。Prasad博士的长期职业目标是成为一名独立的医生科学家，通过优化睡眠和呼吸的干预措施，制定有效的策略，减少不同人群的心血管疾病（CVD）。为了实现她的目标，普拉萨德博士已经组建了一个全面的职业发展计划和一个强大的导师团队，他们拥有长期的退伍军人事务部和其他联邦资助和导师经验。她的主要导师，弗朗西斯M。Weaver博士是VA研究职业科学家和经验丰富的临床试验者。她的共同导师是大卫W. Carley博士（研究阻塞性睡眠呼吸暂停相关自主神经紊乱的专家; OSA和开发新的OSA治疗干预措施）和Samuel T。Kuna，医学博士，在OSA患者的持续气道正压通气（CPAP）治疗干预试验方面具有专业知识，并在VA中有广泛的研究记录。该提案还包括一个多学科的合作者团队，他们在测量OSA高血压发病机制的关键生物标志物，生物医学研究中的遗传祖先，血管功能障碍的早期非侵入性评估和纵向数据分析等领域具有专业知识。该提案利用了Jesse Brown VAMC的广泛研究和临床资源，包括服务的大量不同退伍军人群体。阻塞性睡眠呼吸暂停（OSA）和高血压是非洲裔美国人的常见和严重问题（如国际黑人高血压学会共识声明所述）。CPAP治疗OSA可有效控制OSA患者的高血压，但尚未在非洲裔美国人中进行研究，非洲裔美国人是一种具有潜在巨大健康益处的高危人群。这是一个重要的领域，因为控制不佳的高血压会导致该人群中CVD的进展和发病率。通过在患有高血压和OSA的非洲裔美国人中确定CPAP治疗反应和该反应的相关调节剂，可以实施OSA的靶向治疗，减少CVD的过度负担。我们将在220名患有高血压和新诊断的OSA的非洲裔美国人和欧洲裔美国人退伍军人中确定CPAP治疗（动态血压和中心主动脉血压）对高血压反应的相对幅度（具体目标1）。除了高血压评估外，我们还将测量对CPAP治疗有反应的致病生物标志物（尿累积交感神经系统活性和氧化应激）的变化。此外，我们将在这两个患者人群中检查日间过度嗜睡（EDS）的作用，EDS是治疗反应的潜在重要调节剂（具体目标2）。最后，我们将通过测量遗传祖先（探索性目标）来调整我们对自我认定的非裔美国人预期生物异质性的结果评估。该奖项将为该研究计划的目标提供基础，以减少不同人群中的CVD差异，并有针对性地治疗OSA。

DESCRIPTION (provided by applicant): The candidate for this Clinical Science Research and Development Career Development Award (CDA2) is Bharati Prasad, MD, MS, a pulmonary, critical care, and sleep medicine staff physician at Jesse Brown VAMC. Dr. Prasad's academic appointment is as a tenure-track Assistant Professor at the University of Illinois at Chicago (UIC). Dr. Prasad's long-term career goals are to become an independent physician-scientist developing effective strategies to reduce cardiovascular disease (CVD) in diverse populations through interventions that optimize sleep and breathing. To achieve her goals, Dr. Prasad has assembled a comprehensive career development plan and a strong team of mentors with longstanding VA and other federal funding and mentorship experience. Her primary mentor, Frances M. Weaver PhD, is a VA Research Career Scientist and an experienced clinical trialist. Her co- mentors are David W. Carley, PhD (an expert in autonomic derangements associated with Obstructive Sleep Apnea; OSA and developing novel treatment interventions for OSA) and Samuel T. Kuna, MD, with expertise in Continuous Positive Airway Pressure (CPAP) treatment intervention trials in patients with OSA and an extensive research record in the VA. The proposal also includes a multidisciplinary team of collaborators with expertise in the areas of measurement of biomarkers key to the pathogenesis of hypertension in OSA, genetic ancestry in biomedical research, early non-invasive assessment of vascular dysfunction, and longitudinal data analyses. The proposal leverages the extensive research and clinical resources at Jesse Brown VAMC, including a large pool of diverse Veteran populations served. Obstructive Sleep Apnea (OSA) and hypertension are both common and severe problems in African American individuals (as noted in the International Society on Hypertension in Blacks consensus statement). CPAP treatment of OSA is effective in controlling hypertension in patients with OSA, but has not been studied in African Americans, a high-risk population with potentially large health gains. This is an area of significance because poorly controlled hypertension leads to progression of CVD and morbidity in this population. By identifying CPAP treatment-response and relevant moderators of this response in African Americans with hypertension and OSA, targeted treatment of OSA can be implemented, reducing the excess burden of CVD. We will determine the relative magnitude of hypertension response to CPAP treatment (ambulatory blood pressure and central aortic blood pressure) in 220 African American and European American Veterans with hypertension and newly diagnosed OSA (specific aim 1). We will measure changes in pathogenic biomarkers (urinary cumulative sympathetic nervous system activity and oxidative stress) that are responsive to CPAP treatment in addition to hypertension assessments. Further, we will examine the role of excessive daytime sleepiness (EDS), a potentially important moderator of treatment response, in these two patient populations (specific aim 2). Finally, we will adjust our outcomes assessment for the anticipated biological heterogeneity among self-identified African Americans by measuring genetic ancestry (exploratory aim). This award will provide the foundation for the goals of this research program to reduce CVD disparity in diverse populations with targeted treatment of OSA.