Imaging the Atherosclerosis Cascade in Sleep Apnea

睡眠呼吸暂停在患有潜在心血管疾病的患者中很常见。动脉粥样硬化已经 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，睡眠呼吸暂停和呼吸暂停之间存在独立的联系 在动脉粥样硬化方面，很少有人提供关于睡眠呼吸暂停在 动脉粥样硬化的进展。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，包括内皮功能障碍、血管僵硬、血管炎症、斑块组成 然而，总的斑块负担可能有助于更详细地解开这种关系。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风险 使用持续气道正压治疗。总体而言，这突显了我们目前知识中的一个重大差距 睡眠呼吸暂停与动脉粥样硬化和持续气道正压的机制联系 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 无创量化包括内皮功能障碍在内的整个动脉粥样硬化级联反应的研究 应用颈动脉扩张性磁共振(MR)成像测量外周动脉眼压和血管硬度 (目标1)，使用氟脱氧葡萄糖(FDG)正电子发射断层扫描(PET)的血管炎症，斑块 应用多对比磁共振成像(AIM 2)评价新型睡眠呼吸暂停患者的成分和总斑块负荷 PET/MR联合成像。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，成功完成我们的目标。我们的研究将 提供关于睡眠呼吸暂停在慢性阻塞性肺疾病进展中所起作用的重要的机械性见解 动脉粥样硬化和持续气道正压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)，以识别那些患睡眠呼吸暂停的高危人群。 动脉粥样硬化和对持续正压气道抗动脉粥样硬化反应最强的患者 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风险分层，我们的研究将 为下一个最有效的多部位随机对照试验研究提供关键证据 睡眠呼吸暂停和持续气道正压对儿童睡眠呼吸暂停一级预防和二级预防的影响 心血管事件。

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.