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.

睡眠呼吸暂停在心血管疾病的患者中很常见。动脉粥样硬化已经存在 建议将阻塞性睡眠呼吸暂停与心血管疾病联系起来。虽然 观察性研究的数十年证据表明，睡眠呼吸暂停与 动脉粥样硬化，很少有人就睡眠呼吸暂停在 动脉粥样硬化的进展。对睡眠呼吸暂停中动脉粥样硬化级联的全面评估 患者包括内皮功能障碍，血管僵硬，血管炎症，斑块组成 但是，总的斑块负担可能有助于更详细地解开这种关系。这尤其重要 由于最近的临床试验未能显示出睡眠呼吸暂停治疗的心血管疾病事件风险的降低 使用连续的正气道压力。总体而言，这突出了我们当前知识的主要差距 关于睡眠呼吸暂停与动脉粥样硬化与持续阳性气道压力之间的机械联系 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 进行非侵入性的研究量化了整个动脉粥样硬化级联反应，包括内皮功能障碍 外围动脉静态指导，使用颈动脉扩张性磁共振（MR）成像的血管刚度 （AIM 1），使用氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET），斑块的血管炎症 使用多种对比度MRI（AIM 2）在睡眠呼吸暂停患者中使用新型组成和总斑块负担 组合宠物/MR成像。我们的小组是该领域最有经验的群体之一，我们的研究将 充分利用这种独特的专业知识和技术来成功完成我们的目标。我们的研究愿意 就睡眠呼吸呼吸暂停在进展中的作用提供了重要的机械洞察力 动脉粥样硬化以及连续气道压力疗法的抗动脉粥样硬化作用。 此外，我们的研究将风险分离睡眠呼吸暂停患者（目标3），以确定那些有高风险的患者 动脉粥样硬化以及对连续阳性气道的抗动脉粥样硬化反应最大的动脉粥样硬化 压力。未来的临床试验需要对睡眠呼吸暂停患者进行这种风险分层，我们的研究将 为下一个最高效，多站点，随机对照试验提供了关键证据，以调查 睡眠呼吸暂停和持续阳性气道压力对初级和次要预防的影响 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

Response to letter to the editor for "Self-reported snoring and incident cardiovascular disease events: results from the Jackson Heart Study".

• DOI: 10.1007/s11325-020-02121-1
• 发表时间: 2020-09
• 期刊: Sleep & breathing = Schlaf & Atmung
• 作者: Kundel V;Shah N
• 通讯作者: Shah N

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