Obstructive Sleep Apnea and Associated Pathologic Cardiovascular Phenotypes in Young Individuals: A Comprehensive and Longitudinal Analysis of At-Risk College-Aged Students

年轻个体的阻塞性睡眠呼吸暂停及相关病理性心血管表型：对高危大学生的全面纵向分析

• 批准号: 10585284
• 负责人: Jonathan Ho-Youn Kim
• 金额: $ 67.24万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585284
• 关键词: Age; American; Apnea; Athletic; Blood Vessels; Body Weight Changes; Body mass index; Carbohydrates; Cardiac; Cardiology; Cardiovascular Diseases; Cardiovascular Pathology; Cardiovascular Physiology; Cardiovascular system; Clinical; Clinical Trials; Continuous Positive Airway Pressure; Coupling; Data; Disease; Early treatment; Elderly; Exercise Physiology; Exhibits; Female; Functional disorder; General Population; Goals; Grant; High Prevalence; Hybrids; Hypertension; Image; Impairment; Incidence; Individual; Injury; Intervention Studies; Knowledge; Left; Left Ventricular Mass; Link; Lipids; Lysine; Manufactured football; Measures; Medicine; Metabolic; Metabolism; Modeling; Morbidity - disease rate; Natural experiment; Observational Study; Obstructive Sleep Apnea; Outcome; Pathologic; Patients; Phenotype; Physiologic pulse; Physiological; Plasma; Population; Populations at Risk; Preventive therapy; Public Health; Research Design; Resolution; Risk; Scientist; Series; Sleep; Sports; Students; Subgroup; Testing; Tissues; Training; United States; Ventricular; Weight; Weight Gain; Work; Workload; Youth; aged; amino acid metabolism; arterial stiffness; cardiovascular risk factor; career; cohort; college; effective therapy; experience; experimental study; heart imaging; high risk; improved; indexing; innovation; insight; interest; longitudinal analysis; male; metabolic profile; metabolome; metabolomics; multidisciplinary; novel; novel marker; observational cohort study; physiologic model; prospective; risk stratification; undergraduate student; young man

PROJECT SUMMARY/ABSTRACT vvvvvvv Obstructive sleep apnea (OSA) is highly prevalent across the age spectrum and associated with significant cardiovascular (CV) diseases. To date, our understanding of the association between OSA and CV pathobiology comes from limited cross-sectional data examining older individuals with severe OSA and advanced CV disease, and recent clinical trials have demonstrated OSA treatment in this population does not improve CV outcomes likely because of irreversible CV pathology. The effects of incident and developing OSA on CV phenotypes in younger and healthier individuals remain unknown and whether OSA treatment in this population reverses early CV pathophysiology is uncertain. In my K23, we have demonstrated that OSA is highly prevalent in collegiate American-style football (ASF) athletes, which is a young and healthy population, but also enriched with early traditional CV risk. Our data suggest that OSA in ASF athletes is associated with maladaptive CV functional changes, reduced diastolic function and arterial stiffness; the combination which mirrors the pathophysiology of ventricular-arterial (V-A) uncoupling. New preliminary data also suggest OSA is prevalent among higher-risk female collegiate athletes. We will now leverage our access to at-risk young college-aged individuals to analyze developing OSA and the corollary impact on CV function in absence of confounding and advanced CV morbidity. The scientific premise for the proposed work lies in establishing the pathophysiology that leads to OSA- associated CV disease. Understanding the natural progression of OSA disease could lead to new and effective treatment options for healthier patients prior to irreversible CV pathology, thereby reducing the public health burden of OSA. This prospective and observational cohort study will examine young individuals with OSA using repeated measures analyses and will bring together a multi-disciplinary expert team of scientists from cardiology, exercise physiology, and sleep medicine. We will use a comprehensive array of non-invasive testing including cardiac imaging, vascular function analysis, sleep studies, and plasma metabolomics to characterize the effects of incident and developing OSA on CV function. The working hypotheses are: 1) Independent of weight gain, OSA leads to impaired diastolic function, arterial stiffening, and V-A uncoupling among at-risk young athletes and non-athlete undergraduates with OSA, 2) Changes in OSA observed in detrained individuals will remain associated with CV functional measures, independent of changes in weight, and 3) OSA leads to a specific changes in metabolism that will be associated with CV dysfunction. Aim 1 will investigate the relationship between incident OSA and diastolic function, arterial stiffness, and V-A coupling, adjusting for weight, in a large, multi-center cohort of male ASF athletes, female athletes, and undergraduate controls. Aim 2 will assess the relationship between CV dysfunction and OSA in detrained subjects adjusting for weight change and left ventricular mass regression. Aim 3 will identify the metabolic profile associated with OSA and the association between OSA-specific metabolites and early CV dysfunction.

项目概要/摘要 vvvvvvv 阻塞性睡眠呼吸暂停 (OSA) 在各个年龄段中都非常普遍，并且与显着的相关性相关。 心血管（CV）疾病。迄今为止，我们对 OSA 与 CV 病理学之间关联的理解 来自对患有严重 OSA 和晚期 CV 疾病的老年人进行的有限横截面数据的检查， 最近的临床试验表明，针对该人群的 OSA 治疗并不能改善心血管结局 可能是因为不可逆的心血管病理。 OSA 事件和发展对 CV 表型的影响 更年轻和更健康的个体仍然未知，也不知道该人群的 OSA 治疗是否会提前逆转 CV病理生理学尚不确定。在我的 K23 中，我们已经证明 OSA 在大学中非常普遍 美式橄榄球（ASF）运动员，这是一个年轻健康的群体，而且还富含早期的 传统的CV风险。我们的数据表明 ASF 运动员的 OSA 与适应不良的 CV 功能相关 变化、舒张功能降低和动脉僵硬度；反映病理生理学的组合 心室-动脉（V-A）解偶联。新的初步数据还表明 OSA 在高风险人群中普遍存在 女大学生运动员。我们现在将利用对高危年轻大学生的接触来分析 在没有混杂因素和晚期 CV 发病情况的情况下，发展 OSA 及其对 CV 功能的必然影响。 拟议工作的科学前提在于建立导致 OSA 的病理生理学 相关的心血管疾病。了解 OSA 疾病的自然进展可能会带来新的有效方法 在不可逆的心血管病理发生之前为更健康的患者提供治疗选择，从而降低公众健康 OSA 的负担。这项前瞻性和观察性队列研究将使用以下方法检查患有 OSA 的年轻人 重复测量分析并将汇集来自心脏病学的科学家组成的多学科专家团队， 运动生理学和睡眠医学。我们将使用一系列全面的非侵入性测试，包括 通过心脏成像、血管功能分析、睡眠研究和血浆代谢组学来表征效果 事件和发展 OSA 对 CV 功能的影响。有效假设是：1）与体重增加无关， OSA 会导致高危年轻运动员的舒张功能受损、动脉硬化和 V-A 解偶联 和患有 OSA 的非运动员本科生，2) 在失训者中观察到的 OSA 变化将继续存在 与 CV 功能测量相关，与体重变化无关，并且 3) OSA 会导致特定的 与心血管功能障碍相关的新陈代谢变化。目标 1 将调查关系 事件 OSA 和舒张功能、动脉僵硬度和 V-A 耦合之间的关系，根据体重进行调整， 由男性 ASF 运动员、女性运动员和本科生对照组组成的多中心队列。目标 2 将评估 根据体重变化和左侧调整调整的脱训练者的 CV 功能障碍和 OSA 之间的关系 心室质量回归。目标 3 将确定与 OSA 相关的代谢特征及其关联 OSA 特异性代谢物与早期 CV 功能障碍之间的关系。