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

TIA 中的睡眠呼吸暂停：通过气道正压通气降低心血管风险

• 批准号: 8015911
• 负责人: Dawn Marie Bravata
• 金额: $ 71.99万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015911
• 关键词: Acute; Address; Adherence; Apnea; Cardiovascular Diseases; Cardiovascular system; Carotid Atherosclerotic Disease; Catecholamines; Cessation of life; Cognitive; Collaborations; Congestive Heart Failure; Consensus; Continuous Positive Airway Pressure; Control Groups; Data; Diabetes Mellitus; Diagnosis; Dose; Education; Effectiveness; Enrollment; Event; Future; Glycosylated hemoglobin A; Goals; Health; High Prevalence; Hospitalization; Hour; Indiana; Inflammation; Inflammatory; Injury; Insulin Resistance; Interleukin-6; Intervention; Measures; Mediating; Medical; Minor; Myocardial Infarction; Nature; Obstructive Sleep Apnea; Outcome; Outcome Study; Patients; Plasma; Polysomnography; Population; Prevention strategy; Protocols documentation; Randomized; Randomized Controlled Trials; Research; Research Design; Research Infrastructure; Risk; Risk Marker; Scheme; Severities; Site; Sleep; Sleep Apnea Syndromes; Stroke; Thick; Transient Ischemic Attack; Universities; Vasodilation; Withdrawal; abstracting; cardiovascular risk factor; clinically significant; design; group intervention; heart rate variability; high risk; improved; indexing; intima media; medical schools; new therapeutic target; novel; pressure; prevent; primary outcome; response; secondary outcome; treatment as usual; trend

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)

描述（由申请人提供）： 该提案的目标是开发一种新颖的研究设计，在睡眠呼吸暂停和心血管事件高风险患者中安全且合乎道德地进行长期随机对照试验，以确定有效的气道正压通气 (PAP) 治疗是否会降低睡眠呼吸暂停和心血管事件的风险。心血管风险。短暂性脑缺血发作（TIA）患者睡眠呼吸暂停的患病率很高（60-80%），并且他们在 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，尽管当前的预防策略。因此，睡眠呼吸暂停的治疗可能是减少这一高危人群心血管结局的新治疗目标。拟议的研究是一项针对 TIA 患者的随机对照试验，在 2 个地点（耶鲁大学医学院和印第安纳大学医学院）比较了 12 个月以上的睡眠呼吸暂停诊断和治疗策略与常规护理。 TIA 患者将被随机分配接受常规护理或诊断和治疗方法，包括按 1:2（对照：干预）随机方案进行动态多导睡眠监测和启动自动滴定 CPAP 治疗睡眠呼吸暂停。然后，患有睡眠呼吸暂停的患者将接受标准的 CPAP 治疗干预或旨在提高长期 CPAP 依从性的增强方案。主要目标包括确定此类干预是否会导致心血管风险标志物的多个领域在临床上显着降低、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会导致长期 CPAP 呼吸机依从率的提高。主要和次要结果将包括：(a) CPAP 对心血管风险各个领域的病理生理标志物的影响，包括：炎症（CRP、IL-6）、交感神经活动增强/副交感神经退缩（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（血流介导的血管舒张）和动脉粥样硬化（颈动脉内膜中层厚度）； (b) 长期（12 个月）持续气道正压通气 (CPAP) 坚持； (c) 心血管事件发生率（试点数据）。该拟议项目将提供规划未来在 TIA 患者中进行 CPAP 有效性策略试验所需的数据，以减少心血管事件，并将由先前建立合作关系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。 （摘要完）