The cardiovascular consequences of sleep apnea plus COPD (Overlap syndrome)

摘要 慢性阻塞性肺疾病(COPD)包括慢性支气管炎和 肺气肿)和阻塞性睡眠呼吸暂停(OSA)都是常见的疾病， 心血管后遗症。慢性阻塞性肺疾病和阻塞性睡眠呼吸暂停综合征的并存称为重叠 综合征(OVS)，预后非常差，有心血管死亡的风险。我们的 数据表明，阻塞性睡眠呼吸暂停综合征的治疗与个体死亡率的提高有关 对于OVS，但到目前为止，数据还不是决定性的，基本机制也没有定义。从理论上讲， 在基线(持续性)低氧血症患者中，由于OSA导致的进一步间歇性低氧血症 可能促进肺血管收缩和肺血管阻力升高。因此， 右心室(RV)可能受OVS的影响特别大。值得注意的是，我们有强劲的初步数据 显示OVS对RV的影响以及干预后的可逆性。为了调查这些 概念进一步，我们提出了两个具体目标。首先，我们将进行一项横断面研究， 比较OSA、COPD和OVS患者心血管风险的特定指标。这 AIM将验证这样的假设，即与OVS相比，OVS的内皮功能恶化 单独患有任何一种疾病的人。我们将量化心血管疾病的其他标志物 风险，如心脏核磁共振和血浆生物标记物，包括新的microRNA。我们最近有 大量文献表明miR-210在阻塞性睡眠呼吸暂停综合征的发病机制中起重要作用 血管风险。我们还将使用新的成像方法来评估潜在的生物标志物 机械的洞察力，并为后续研究确定可靠的替代结果衡量标准。 其次，我们将进行一项机械性的临床研究，以比较RV质量的改善 接受双水平气道正压(PAP)的个体与个体相比 他们接受氧气(O2)，这是目前的护理标准。这一目标将检验这一假设 与氧气疗法相比，双水平PAP疗法改善了心血管风险的标记物。 除了心脏核磁共振，我们还将评估心血管风险的其他生物标记物，如目标1所示。 这些发现将为多中心随机对照试验奠定基础，我们相信这将 被要求改变目前的护理标准。我们的提案还将为基础研究提供信息 论持续性低氧血症与间歇性低氧血症的相互作用。考虑到高血管风险人群 这些人，非常高的人口疾病患病率和缺乏最新数据， 进一步的机械论研究势在必行。

Abstract Chronic obstructive pulmonary disease (COPD, which includes chronic bronchitis and emphysema) and obstructive sleep apnea (OSA) are both common diseases with major cardiovascular sequelae. The concomitant presence of COPD and OSA is referred to as overlap syndrome (OVS), which has a very poor prognosis with his risk of cardiovascular mortality. Our data demonstrate an association between OSA treatment and improved mortality in individuals with OVS, but to date data are not definitive and underlying mechanisms are undefined. In theory, in individuals with baseline (sustained) hypoxemia, further intermittent hypoxemia due to OSA may promote pulmonary vasoconstriction and elevated pulmonary vascular resistance. Thus, the right ventricle (RV) may be particularly affected by OVS. Of note, we have robust preliminary data showing the impact of OVS on the RV and reversibility with intervention. To investigate these concepts further, we propose two specific aims. First, we will perform a cross-sectional study to compare specific markers of cardiovascular risk among those with OSA vs. COPD vs. OVS. This aim will test the hypothesis that OVS has worsen endothelial function as compared with individuals afflicted with either disease alone. We will quantify other markers of cardiovascular risk such as cardiac MRI and plasma biomarkers including novel microRNAs. We have recent prominent publications suggesting a major role of miR-210 in the pathogenesis of OSA induced vascular risk. We will also employ novel imaging methods to assess potential biomarkers for mechanistic insights and to identify robust surrogate outcome measures for subsequent studies. Second, we will perform a mechanistic clinical study to compare the improvement in RV mass among individuals who receive bi-level positive airway pressure (PAP) as compared to individuals who receive oxygen (O2), which is the current standard of care. This aim will test the hypothesis that bi-level PAP therapy improves markers of cardiovascular risk as compared with O2 therapy. In addition to cardiac MRI we will assess other biomarker of cardiovascular risk as in Aim 1. Such findings will lay the groundwork for a multicenter randomized controlled trial, which we believe will be required to change the current standard of care. Our proposal will also inform basic research on the interactions of sustained plus intermittent hypoxemia. Given the high vascular risk among these individuals, the very high population prevalence of disease and the lack of current data, further mechanistic research is imperative.