Sleep Apnea in TIA: Reducing Cardiovascular Risk with Positive Airway Pressure

描述(由申请人提供)： 这项建议的目标是开发一种新的研究设计，在睡眠呼吸暂停和心血管事件的高危患者中安全和合乎伦理地进行长期随机对照试验，以确定有效的气道正压(PAP)治疗是否降低心血管风险。短暂性脑缺血发作(TIA)患者睡眠呼吸暂停发生率高(60%-80%)，尽管有现有的预防策略，但他们在1年内发生心血管事件(心肌梗死、充血性心力衰竭、完全性中风和心血管死亡)的风险很高。因此，睡眠呼吸暂停的治疗可能代表着一个新的治疗目标，以减少这一高危人群的心血管结局。这项拟议的研究是一项针对短暂性脑缺血发作患者的随机对照试验，比较了两个地点(耶鲁大学医学院和印第安纳大学医学院)在12个月内诊断和治疗睡眠呼吸暂停的策略和常规护理。TIA患者将被随机分配到常规护理或诊断和治疗方法中，其中包括动态多导睡眠监测和在1：2(对照：干预)随机方案中开始对睡眠呼吸暂停患者进行CPAP自动滴定。然后，患有睡眠呼吸暂停的干预患者将接受标准的CPAP治疗干预或旨在增加长期CPAP依从性的增强方案。主要目标将包括确定这种干预是否导致心血管风险标志物的几个领域在临床上显著减少，实现这些改善的最佳依从性水平，以及增强的干预方案是否导致长期CPAP依从率的提高。主要和次要结果将包括：(A)CPAP对心血管风险不同领域的病理生理标记物的影响，包括：炎症(CRP，IL-6)，交感活动/副交感神经活动增加(血浆儿茶酚胺和心率变异性(HRV))，胰岛素抵抗(HOMA-IR，HbA1C)，内皮损伤(血流介导的血管扩张)和动脉粥样硬化(颈动脉内膜中层厚度)；(B)长期(12个月)CPAP坚持；以及(C)心血管事件发生率(试点数据)。这一拟议的项目将提供在短暂性脑缺血发作患者中计划未来CPAP有效性策略试验所需的数据，以减少心血管事件，并将由一个先前已形成合作的跨学科研究团队进行，从而利用我们重要的现有基础设施。 (摘要结束)

DESCRIPTION (provided by applicant): The goal of this proposal is to develop a novel study design to safely and ethically conduct a long-term randomized controlled trial among patients at high risk for both sleep apnea and cardiovascular events in order to determine whether effective positive airway pressure (PAP) therapy reduces cardiovascular risk. Patients with transient ischemic attack (TIA) have a high prevalence of sleep apnea (60-80%), and they are at high risk within 1 year for cardiovascular events (myocardial infarction, congestive heart failure, completed stroke, and cardiovascular death) despite current preventive strategies. Therefore, the treatment of sleep apnea may represent a novel therapeutic target to reduce cardiovascular outcomes in this high risk population. The proposed study is a randomized controlled trial among patients with TIA comparing strategies for the diagnosis and treatment of sleep apnea with usual care over 12 months at 2 sites (Yale University School of Medicine and Indiana University School of Medicine). Patients with TIA will be randomly assigned to either usual care or a diagnosis and treatment approach that includes ambulatory polysomnography and initiation of autotitrating CPAP for sleep apnea in a 1:2 (control: intervention) randomization scheme. Intervention patients with sleep apnea will then receive either a standard CPAP treatment intervention or an enhanced protocol designed to increase long-term CPAP adherence. The Primary Aims will consist of determining whether such an intervention results in clinically significant reductions in several domains of markers of cardiovascular risk, the optimal adherence levels to achieve these improvements, and whether an enhanced intervention protocol results in improved long-term CPAP adherence rates. The primary and secondary outcomes will include: (a) the impact of CPAP on pathophysiologic markers in various domains of cardiovascular risk including: inflammation (CRP, Il-6), heightened sympathetic activity/parasympathetic withdrawal (plasma catecholamines and heart rate variability (HRV)), insulin resistance (HOMA-IR, HbA1C), endothelial injury (flow mediated vasodilation), and atherosclerosis (carotid intima-media thickness); (b) long term (12 month) CPAP adherence; and (c) cardiovascular event rate (pilot data). This proposed project will provide the data needed to plan a future effectiveness strategy trial of CPAP among patients with TIA to reduce cardiovascular events, and will be conducted by a transdisciplinary research team that has a previously formed collaboration, thus leveraging our significant existing infrastructure. (End of Abstract)