Imaging the Atherosclerosis Cascade in Sleep Apnea

睡眠呼吸暂停中动脉粥样硬化级联的成像

• 批准号: 10408815
• 负责人: neomi A shah
• 金额: $ 84.53万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10408815
• 关键词: 3-Dimensional; Affect; Age; Apnea; Area; Atherosclerosis; Beds; Blood Vessels; Body mass index; Cardiovascular Diseases; Cardiovascular system; Clinical; Clinical Trials; Continuous Positive Airway Pressure; Devices; Dose; Event; Future; Glucose; Goals; Hemorrhage; Hour; Image; Individual; Inflammatory; Knowledge; Link; Lipids; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Newly Diagnosed; Observational Study; Obstructive Sleep Apnea; Patients; Peripheral; Play; Positron-Emission Tomography; Primary Prevention; Randomized Controlled Trials; Risk; Role; Rupture; Secondary Prevention; Severities; Site; Sleep Apnea Syndromes; Subgroup; Technology; Thick; arterial tonometry; atherosclerosis risk; base; calcification; cardiovascular disorder prevention; cytokine; endothelial dysfunction; experience; glucose uptake; high risk; improved; indexing; innovation; insight; novel; primary outcome; reactive hyperemia; response; risk stratification; sex; vascular inflammation

Sleep apnea is common among patients with underlying cardiovascular disease. Atherosclerosis has been suggested as an intermediary mechanism linking obstructive sleep apnea to cardiovascular disease. Although decades of evidence from observational studies suggests an independent link between sleep apnea and atherosclerosis, few have provided significant mechanistic insight regarding the role sleep apnea plays in the progression of atherosclerosis. A comprehensive assessment of the atherosclerosis cascade in sleep apnea patients, which includes endothelial dysfunction, vascular stiffness, vascular inflammation, plaque composition and total plaque burden may however help unravel this relationship in more detail. This is especially important as recent clinical trials fail to show a reduction in cardiovascular disease event risk with sleep apnea treatment using continuous positive airway pressure. Collectively, this highlights a major gap in our current knowledge about the mechanistic link between sleep apnea and atherosclerosis and continuous positive airway pressure's anti-atherosclerotic actions (or lack of). In order to fill the above-mentioned knowledge gaps, we propose a study to non-invasively quantify the entire atherosclerosis cascade including endothelial dysfunction using peripheral arterial tonometry, vascular stiffness using carotid distensibility magnetic resonance (MR) imaging (Aim 1), vascular inflammation using fluoro deoxy glucose (FDG) positron emission tomography (PET), plaque composition and total plaque burden using multi-contrast MRI (Aim 2) in sleep apnea patients using novel combined PET/MR imaging. Our group is one of the most experienced groups in this field and our study will take full advantage of this unique expertise and technology to successfully complete our goals. Our study will provide significant mechanistic insight regarding the role sleep apnea plays in the progression of atherosclerosis and regarding the anti-atherosclerotic actions of continuous positive airway pressure therapy. Furthermore, our study will risk-stratify sleep apnea patients (Aim 3) to identify those at high risk for atherosclerosis and those with the greatest anti-atherosclerotic response to continuous positive airway pressure. Future clinical trials are in need of such risk stratification of sleep apnea patients and our study will provide this crucial evidence for the next most efficient, multi-site, randomized controlled trial to investigate sleep apnea's and continuous positive airway pressure's impact on primary and secondary prevention of cardiovascular events.

睡眠呼吸暂停在有潜在心血管疾病的患者中很常见。Atherplane已经 被认为是阻塞性睡眠呼吸暂停与心血管疾病之间的中介机制。虽然 数十年的观察性研究证据表明，睡眠呼吸暂停与 虽然睡眠呼吸暂停在动脉粥样硬化中的作用，但很少有人提供关于睡眠呼吸暂停在动脉粥样硬化中所起作用的重要机制见解。 动脉粥样硬化的进展。对睡眠呼吸暂停患者动脉粥样硬化级联反应的综合评估 患者，其中包括内皮功能障碍，血管僵硬，血管炎症，斑块组成 和总的牙菌斑负荷可能有助于更详细地阐明这种关系。这一点尤其重要 由于最近的临床试验未能显示睡眠呼吸暂停治疗可降低心血管疾病事件的风险 使用持续气道正压通气总的来说，这突出了我们目前知识的一个主要差距 关于睡眠呼吸暂停和动脉粥样硬化之间的机械联系， 抗动脉粥样硬化作用（或缺乏）。为了填补上述知识空白，我们提出了一个 一项使用非侵入性定量包括内皮功能障碍在内的整个动脉粥样硬化级联的研究 外周动脉张力测定，使用颈动脉扩张性磁共振（MR）成像的血管硬度 (Aim 1）、血管炎症使用氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET），斑块 使用新型多对比MRI（Aim 2）在睡眠呼吸暂停患者中检测斑块组成和总斑块负荷 联合PET/MR成像。我们小组是这一领域最有经验的小组之一，我们的研究将 充分利用这一独特的专业知识和技术，成功地完成我们的目标。我们的研究将 提供了关于睡眠呼吸暂停在以下进展中所起作用的重要机制性见解： 动脉粥样硬化和关于持续气道正压通气治疗的抗动脉粥样硬化作用。 此外，我们的研究将对睡眠呼吸暂停患者进行风险分层（目标3），以确定那些高风险的睡眠呼吸暂停患者。 动脉粥样硬化和对持续气道正压通气有最大抗动脉粥样硬化反应的患者 压力未来的临床试验需要对睡眠呼吸暂停患者进行这样的危险分层，我们的研究将 为下一个最有效的、多中心的、随机对照试验提供关键证据， 睡眠呼吸暂停和持续气道正压通气对一级和二级预防影响 心血管事件。

项目成果

Modifying pathways by age and sex for the association between combined sleep disordered breathing and long sleep duration with neurocognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

• DOI: 10.1002/alz.12361
• 发表时间: 2021-12
• 期刊: Alzheimer's & dementia : the journal of the Alzheimer's Association
• 作者: Kaur SS;Tarraf W;Wu B;Gonzalez KA;Daviglus M;Shah N;Sotres-Alvarez D;Gallo LC;Wohlgemuth W;Redline S;Gonzalez HM;Ramos AR
• 通讯作者: Ramos AR

Advanced Proteomics and Cluster Analysis for Identifying Novel Obstructive Sleep Apnea Subtypes before and after Continuous Positive Airway Pressure Therapy.

先进的蛋白质组学和聚类分析用于识别连续气道正压治疗前后新型阻塞性睡眠呼吸暂停亚型。

• DOI: 10.1513/annalsats.202210-897oc
• 发表时间: 2023
• 期刊: Annals of the American Thoracic Society
• 影响因子: 8.3
• 作者: Kundel,Vaishnavi;Cohen,Oren;Khan,Samira;Patel,Manishkumar;Kim-Schulze,Seunghee;Kovacic,Jason;Suárez-Fariñas,Mayte;Shah,NeomiA
• 通讯作者: Shah,NeomiA

Novel non-invasive assessment of upper airway inflammation in obstructive sleep apnea using positron emission tomography/magnetic resonance imaging.

• DOI: 10.1007/s11325-021-02480-3
• 发表时间: 2022-09
• 期刊: Sleep & breathing = Schlaf & Atmung
• 作者: Cohen O;John MM;Kaufman AE;Kundel V;Burschtin O;Khan S;Fayad Z;Mani V;Shah NA
• 通讯作者: Shah NA

Association Between Sleep Disordered Breathing and Left Ventricular Function: A Cross-Sectional Analysis of the ECHO-SOL Ancillary Study.

• DOI: 10.1161/circimaging.119.009074
• 发表时间: 2020-05
• 期刊: Circulation. Cardiovascular imaging
• 作者: Ogilvie RP;Genuardi MV;Magnani JW;Redline S;Daviglus ML;Shah N;Kansal M;Cai J;Ramos AR;Hurwitz BE;Ponce S;Patel SR;Rodriguez CJ
• 通讯作者: Rodriguez CJ

Sleep duration and vascular inflammation using hybrid positron emission tomography/magnetic resonance imaging: results from the Multi-Ethnic Study of Atherosclerosis.

使用混合正电子发射断层扫描/磁共振成像的睡眠持续时间和血管炎症：动脉粥样硬化多种族研究的结果。

• DOI: 10.5664/jcsm.9382
• 发表时间: 2021
• 期刊: Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
• 作者: Kundel,Vaishnavi;Reid,Michelle;Fayad,Zahi;Ayappa,Indu;Mani,Venkatesh;Rueschman,Michael;Redline,Susan;Shea,Steven;Shah,Neomi
• 通讯作者: Shah,Neomi