Reversibility of Cardiovascular Injury with CPAP Use: Mechanisms Involved

描述（由申请人提供）： 在中年人中，阻塞性睡眠呼吸暂停（OSA）的患病率在男性中至少为4%，在女性中至少为2%，并且可能会随着肥胖症在这个国家的流行而增加。OSA患者发生致命性和非致命性心血管疾病（CVD）事件的风险增加。持续气道正压通气（CPAP）治疗可以降低CVD风险;然而，其机制，时间过程和益处的持久性尚不清楚。这些是特别重要的问题，因为OSA患者通常不依从或间歇性依从CPAP治疗。本研究提案描述了我们的计划，以评估CPAP治疗对两种动脉功能指标（即动脉硬度和内皮依赖性血管舒张）的影响的时间过程和幅度。本研究有四个具体目标，涉及四个相互关联的假设：确定（i）CPAP治疗是否降低颈动脉-股动脉脉搏波速度（主动脉僵硬的标志物），（ii）CPAP治疗是否改善肱动脉的血流介导的血管舒张（内皮功能的标志物），（iii）CPAP治疗观察到的动脉功能变化的时间过程及其停止治疗后的持续时间，以及（iv）在OSA患者中观察到的冠状动脉血流调节在CPAP治疗后是否改善。多模态无创心脏和血管成像将用于前瞻性研究130名CPAP初治成人（21-45岁）中重度OSA患者在开始CPAP治疗前、4周和12周后以及停药后712天的这些目标。本研究将有足够的把握度调整可能的混杂因素，如肥胖程度、嗜睡、性别、种族和CPAP依从性。这项培训补助金和研究将为申请人提供培训和研究经验，使她成为一名独立的调查员，设计和进行严格的以患者为导向的研究项目，与睡眠障碍和心血管疾病。Korcarz博士的长期职业目标是成为一名独立的研究人员，从事与睡眠障碍和心血管疾病风险相关的尖端生理学研究。 公共卫生相关性： 阻塞性睡眠呼吸暂停（OSA）是一种可治疗的高度流行的疾病，通常诊断不足。OSA与致命性和非致命性心血管疾病事件的风险增加有关。该提案评估了持续气道正压通气（CPAP）治疗对动脉功能的两项指标（特别是动脉硬度和内皮功能）的影响，基于持续时间和CPAP依从性的影响程度，以及早期停药后其有益作用的可逆性。

DESCRIPTION (provided by applicant): The prevalence of Obstructive Sleep Apnea (OSA) in middle-aged adults is at least 4% in males and 2% in females and will probably increase with the obesity epidemic in this country. Individuals with OSA are at increased risk for fatal and non-fatal cardiovascular disease (CVD) events. Treatment with continuous positive airway pressure (CPAP) may reduce CVD risk; however, the mechanisms, time course, and durability of its benefit are not known. These are especially important issues since patients with OSA often are not compliant or are intermittently compliant with CPAP therapy. This research proposal describes our plans to evaluate the time course and magnitude of the effects of CPAP therapy on two measures of arterial function, namely arterial stiffness and endothelium-dependent vasodilation. This study has four specific aims that address four inter- related hypotheses: To determine if (i) CPAP therapy reduces carotid-to-femoral pulse wave velocity, a marker of aortic stiffness, (ii) CPAP therapy improves flow-mediated vasodilation of the brachial artery, a marker of endothelial function, (iii) the time course of changes in arterial function observed with CPAP therapy and their duration after cessation of therapy, and (iv) if coronary artery flow regulation observed in patients with OSA improves after CPAP therapy. Multimodality non-invasive cardiac and vascular imaging will be used to prospectively investigate these aims in 130 CPAP-naive adults (21-45 years old) with moderate to severe OSA, before starting CPAP therapy, after 4 and 12 weeks, and then 712 days after withdrawal. This study will have adequate power to adjust for possible confounders such as degree of obesity, sleepiness, sex, race, and CPAP compliance. This training grant and research study will provide the applicant with training and research experiences to permit her to become an independent investigator that designs and conducts rigorous patient- oriented research projects related to sleep disorders and CVD. Dr. Korcarz's long-term career goal is to be an independent investigator that performs cutting edge physiological research related to sleep disorders and cardiovascular disease risk. PUBLIC HEALTH RELEVANCE: Project Narrative Obstructive Sleep Apnea (OSA) is a treatable and highly prevalent condition that often remains underdiagnosed. OSA is linked to increased risk for fatal and non-fatal cardiovascular disease events. This proposal evaluates the effects of Continuous Positive Airway Pressure (CPAP) therapy on two measures of arterial function, specifically arterial stiffness and endothelial function, the magnitude of the effect based on duration and CPAP compliance, as well as the reversibility of it's beneficial effects after early withdrawal.