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）： 该提案的目的是开发一种新的研究设计，在睡眠呼吸暂停和心血管事件高风险患者中安全和伦理地进行长期随机对照试验，以确定有效的气道正压通气（PAP）治疗是否降低心血管风险。短暂性脑缺血发作（TIA）患者的睡眠呼吸暂停患病率较高（60-80%），尽管目前采取了预防措施，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、完全性卒中和心血管死亡）的风险较高。因此，睡眠呼吸暂停的治疗可能代表了一种新的治疗目标，以减少这一高危人群的心血管结局。拟议的研究是一项在TIA患者中进行的随机对照试验，比较了2个地点（耶鲁大学医学院和印第安纳州大学医学院）12个月内睡眠呼吸暂停的诊断和治疗策略。TIA患者将被随机分配至常规护理或诊断和治疗方法，包括以1：2（对照：干预）的随机化方案进行动态多导睡眠描记术和启动自动滴定CPAP治疗睡眠呼吸暂停。然后，患有睡眠呼吸暂停的干预患者将接受标准CPAP治疗干预或旨在提高长期CPAP依从性的增强方案。主要目的将包括确定此类干预是否导致心血管风险标志物的几个领域的临床显著降低，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导致改善的长期CPAP依从率。主要和次要结局将包括：（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，HbA 1C），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）持续气道正压通气依从性;和（C）心血管事件发生率（试点数据）。该拟议项目将提供计划未来在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，并将由一个跨学科研究团队进行，该团队先前已形成合作，从而利用我们现有的重要基础设施。 (End摘要）