Targeted Treatment of Obstructive Sleep Apnea to Reduce Cardiovascular Disparity

本届临床科学研究与发展职业发展奖候选人 (CDA2)是Bharati Prasad，医学博士，医学硕士，肺部、危重护理和睡眠医学助理医生，位于 杰西·布朗·瓦姆克。普拉萨德博士的学术任命是作为终身教职的助理教授 伊利诺伊大学芝加哥分校(UIC)。普拉萨德博士的长期职业目标是成为一名 独立内科医生-科学家制定有效策略减少心血管疾病(CVD) 在不同的人群中，通过优化睡眠和呼吸的干预措施。为了实现她的目标， 普拉萨德博士制定了全面的职业发展计划和强大的导师团队 拥有长期的退伍军人事务部和其他联邦资助和指导经验。她的主要导师， 弗朗西斯·M·韦弗博士，退伍军人研究职业科学家和经验丰富的临床试验人员。她的搭档- 导师是David W.Carley博士(与梗阻相关的自主神经紊乱方面的专家 睡眠呼吸暂停；阻塞性睡眠呼吸暂停和开发阻塞性睡眠呼吸暂停的新治疗干预措施)和塞缪尔·T·库纳，医学， 在患者的持续正压(CPAP)治疗干预试验方面拥有专业知识 并在退伍军人事务部有广泛的研究记录。该提案还包括一个多学科的 在生物标志物测量领域拥有专业知识的合作者团队 阻塞性睡眠呼吸暂停综合征中高血压的发病机制，生物医学研究中的遗传祖先，早期非侵入性 血管功能障碍的评估，以及纵向数据分析。该提案充分利用了 杰西·布朗VAMC的广泛研究和临床资源，包括大量不同的 退伍军人服务过。阻塞性睡眠呼吸暂停(OSA)和高血压都很常见 非洲裔美国人的严重问题(如国际高血压学会所指出的 在黑人共识声明中)。CPAP治疗阻塞性睡眠呼吸暂停综合征有效控制高血压 阻塞性睡眠呼吸暂停综合征患者，但尚未在非洲裔美国人中进行研究，这是一个潜在的高危人群 巨大的健康收益。这是一个有意义的领域，因为高血压控制不佳会导致 这一人群中心血管疾病的进展和发病率。通过确定CPAP治疗反应和 患有高血压和阻塞性睡眠呼吸暂停综合征的非裔美国人的这种反应的相关调节者，有针对性 可以实施阻塞性睡眠呼吸暂停综合征的治疗，减轻心血管疾病的过重负担。我们将确定 CPAP治疗对高血压反应的相对大小(动态血压和 220名非裔美国人和欧洲裔美国退伍军人的中心动脉血压 高血压和新诊断的OSA(特定目标1)。我们将测量病原菌的变化 生物标志物(尿交感神经系统累积活性和氧化应激) 除高血压评估外，对CPAP治疗有反应。此外，我们将研究 日间过度嗜睡(EDS)是治疗反应的一个潜在的重要调节因素，在 这两个患者群体(特定目标2)。最后，我们将调整我们的结果评估，以 通过测量基因在自我认同的非裔美国人中预期的生物异质性 祖先(探索性目标)。该奖项将为本研究的目标奠定基础。 通过有针对性地治疗阻塞性睡眠呼吸暂停综合征来减少不同人群的心血管疾病差异的计划。

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.