Patterns of Cardiopulmonary health across the life course

摘要 慢性肺病和心力衰竭(HF)非常普遍，通常同时发生，并与 严重的发病率和死亡率。我们小组和其他人的工作证明了一个独立的 慢性肺部疾病与发生的心衰之间的关系，可能部分是由炎症驱动的。我们有 还证明，即使在没有症状性肺部疾病的情况下，肺功能受损也是由 肺活量测定与超声心动图显示的心脏重构不良和发生心力衰竭事件有关。而当 有症状的肺部疾病和心力衰竭常发生在老年人，许多年轻人相对没有症状 肺健康和心脏结构和功能受损。这些亚临床心肺异常 在从青壮年到中年的关键变化期发展。然而，数据在上是稀疏的 从健康到疾病从青壮年到中年过渡的时间和相关机制， 以及相关的种族性别差异。如果不识别这些独特的变化模式，就不可能 筛查亚临床变化，并在肺和肺不可逆损害之前采取预防策略 心。这需要在最早可检测到的变化时进行上游识别。而肺活量测定仪是黄金 作为肺部疾病检测的标准，它是一个相对粗略和不敏感的肺健康受损的指标。在……里面 相比之下，肺损伤(使用我们小组开发和验证的一种新的局部直方图分析进行量化) CT扫描是肺健康受损的更敏感和更早的指标(例如 烟草、空气污染和呼吸道病毒感染)。因此，我们现在建议利用 青年冠状动脉风险发展(CARDIA)研究的独特平台 从心肺健康向疾病转变的关系和机制。到目前为止，我们 该小组在CARDIA中分别调查了肺健康受损和心力衰竭的预测因素和后果。 在这个项目中，我们将在先前工作的基础上，通过分析CT扫描来确定 肺损伤和不利的心脏重构，并通过分析大量的血液基础来确定机制 生物标志物(使用多路复用阵列)和执行4维血流心血管磁共振 成像(CMRI)。我们将测试这一假设，即详细的成像和基于血液的标志物可以在临床上提供信息 反映关键时期肺损伤和不良心脏重塑动态变化的相关内型 通过以下几个具体目标确定生命脆弱期之间的纵向关联性 肺损伤和左心室舒张末容量(LVEDV)；(2)确定亚临床和临床性心衰的风险 在关节肺损伤和LVEDV轨迹组之间；以及(3)确定 肺损伤与心脏不良重塑的关系。这项研究将调查相关的因素 从心肺健康到疾病的过渡以及相关机制，在这样做的过程中，将确定 筛选策略并为肺病和心脏病的靶向疾病拦截贡献新的途径。

ABSTRACT Chronic lung disease and heart failure (HF) are highly prevalent, commonly co-occur, and are associated with significant morbidity and mortality. Work from our group and others has demonstrated an independent relationship between chronic lung disease and incident HF that may be driven in part by inflammation. We have also documented that even in the absence of symptomatic lung disease, impaired lung function defined by spirometry is associated with adverse cardiac remodeling on echocardiography and incident HF events. While symptomatic lung disease and HF often occur in the elderly, many younger adults have relatively asymptomatic impairment in lung health and cardiac structure and function. These subclinical cardiopulmonary abnormalities develop during the key modifiable period from young adulthood to midlife. However, data are sparse on the timing and associated mechanisms of the transition from health to disease spanning young adulthood to midlife, and related race-sex differences. Without identifying these unique patterns of change, it will not be possible to screen for subclinical changes and employ prevention strategies prior to irreversible damage in the lung and heart. This requires upstream identification at the earliest detectable change. While spirometry is the gold standard for lung disease detection, it is a relatively crude and insensitive measure of impaired lung health. In contrast, lung injury (quantified using a novel local histogram analysis developed and validated by our group) from computed tomography (CT) scans is a more sensitive and earlier indicator of impaired lung health (e.g. due to tobacco, air pollution, and respiratory viral infection). Therefore, we now propose to take advantage of the Coronary Artery Risk Development in Young Adults (CARDIA) study’s unique platform to study the temporal relationship of and mechanisms underlying the transition from lung and heart health to disease. To-date, our group has investigated the predictors and consequences of impaired lung health and HF, separately, in CARDIA. In this project, we will build upon our prior work by analyzing CT scans to determine the concurrent evolution of lung injury and adverse cardiac remodeling and identify mechanisms by assaying a multitude of blood-based biomarkers (using a multiplexed array) and performing 4-dimensional flow cardiovascular magnetic resonance imaging (cMRI). We will test the hypothesis that detailed imaging and blood-based markers can inform clinically relevant endotypes reflecting dynamic changes in lung injury and adverse cardiac remodeling during a key vulnerable period of life through the following specific aims: (1) Determine the longitudinal association between lung injury and left ventricular end-diastolic volume (LVEDV); (2) Determine the risk of subclinical and clinical HF among joint lung injury and LVEDV trajectory groups; and (3) Determine the hemodynamic mediators of the association between lung injury and adverse cardiac remodeling. This study will investigate factors associated with transitions from cardiopulmonary health to disease and associated mechanisms, and in doing so, will identify screening strategies and contribute novel pathways for targeted disease interception of lung and heart disease.