Novel physiologically-driven phenotypes for the prognosis of cardiovascular outcomes in sleep apnea: Toward precision medicine in sleep health

用于睡眠呼吸暂停心血管结局预后的新型生理驱动表型：迈向睡眠健康的精准医学

• 批准号: 10577765
• 负责人: Ali Azarbarzin
• 金额: $ 12.96万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10577765
• 关键词: Acute; Adult; Age; Apnea; Area; Atherosclerosis; Biological; Cardiac; Cardiac health; Cardiometabolic Disease; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Classification; Clinical; Clinical Trials; Cohort Studies; Communities; Coronary heart disease; Data; Development; Devices; Diabetes Mellitus; Diagnosis; Discrimination; Disease; Disease Outcome; Drops; Early Intervention; Equation; Event; Foundations; Frequencies; Health; Health Benefit; Heart Rate; Heart failure; Heterogeneity; Hispanic Community Health Study; Hispanic Community Health Study/Study of Latinos; Home; Hypertension; Hypoxemia; Hypoxia; Individual; Jackson Heart Study; Lead; Link; Measures; Meta-Analysis; Metabolic; Metadata; Morbidity - disease rate; Multi-Ethnic Study of Atherosclerosis; Myocardial Infarction; Obstructive Sleep Apnea; Outcome; Oxygen; Participant; Patient Selection; Phenotype; Physiological; Play; Polysomnography; Population; Prognosis; Prognostic Marker; Prospective, cohort study; Pulse Oximetry; ROC Curve; Race; Research; Risk; Risk Factors; Sampling; Severities; Signal Transduction; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Fragmentations; Stroke; Study of Latinos; Subgroup; Testing; Time; Wisconsin; Work; adverse outcome; airway obstruction; cardiometabolism; cardiovascular disorder risk; cohort; comorbidity; ethnic diversity; high risk; high risk population; improved; indexing; individual patient; mortality; novel; older men; personalized medicine; phenotypic biomarker; precision medicine; predictive modeling; respiratory; response; risk prediction; sex; sleep health

PROJECT SUMMARY/ABSTRACT Obstructive sleep apnea is a serious condition associated with increased risk for major comorbidities, including hypertension, diabetes, and an increased risk of cardiovascular diseases (CVD) and mortality. The repetitive cycles of apnea/hypopnea during sleep lead to frequent drops in oxygen saturation and cardiac autonomic surges following obstructive respiratory events. These acute and repeated physiological changes are thought to play a key role in the development of adverse cardiometabolic consequences. Observational community-based cohort studies have shown strong associations of OSA with CVD outcomes. However, it has been challenging to identify/predict high risk individuals potentially due to substantial heterogeneity in OSA population. A potential explanation is the inability of apnea hypopnea index (AHI), the main metric for OSA diagnosis and management, to capture the heterogeneity in the OSA-related hypoxemia and autonomic responses during sleep. More importantly, these physiological changes are thought to vary by age, sex, and race. Therefore, the identification of phenotypic markers that better quantify OSA-specific hypoxemia and autonomic responses are needed to provide improved prediction of incident cardiometabolic outcomes. Herein, we propose to study two novel physiological phenotypes that can be readily extracted from pulse oximetry signal, the Sleep Apnea Specific Hypoxic Burden (“SASHB”) and the heart rate response to apneas/hypopneas (“∆HR”). We will use well-defined large community based prospective cohort studies, including the Sleep Heart Health study (SHHS), Multiethnic Study of Atherosclerosis (MESA), Hispanic community health study of Latinos (HCHS/SOL), the Outcomes of Sleep Disorders in Older Men (MrOS), and the Jackson Heart Study (JHS), and the Wisconsin Sleep Cohort (WSC) to pursue the following Aims. In Aim 1, we plan to use individual participant meta-analysis to examine how SASHB/∆HR determine the incident hypertension, diabetes, and CVD in adults with diverse ethnicity/background. Past studies have shown that the strength of associations between OSA, as quantified by AHI, and outcomes vary by age, sex, and race. It is unclear if this observation was due to underlying biological differences or the inability of AHI to capture the heterogeneity in OSA. In Aim 1(a), we plan to test the extent to which the associations of SASHB/∆HR and incident diabetes, hypertension, and CVD vary by age, sex, and race. Finally, in Aim 2, we plan to test the added value of SASHB/∆HR in predicting an established 10-year CVD risk (Pooled Cohort Equations to estimate the atherosclerotic cardiovascular disease) in comparison with AHI and other conventional CVD risk factors. Overall, our proposal is expected to demonstrate that SASHB/∆HR are more strongly linked with adverse cardiometabolic outcomes across the community and improve CVD risk prediction. Furthermore, given that these phenotypes can be easily extracted from home sleep testing devices, this personalized medicine approach will potentially alter the paradigm of OSA assessment and management in the community.

项目概要/摘要 阻塞性睡眠呼吸暂停是一种严重疾病，会增加主要合并症的风险，包括高血压、 糖尿病，以及心血管疾病 (CVD) 和死亡风险增加 呼吸暂停/呼吸不足的重复循环。 睡眠期间导致血氧饱和度频繁下降和阻塞性呼吸后心脏自主神经激增 这些急性和重复的生理变化被认为在不良事件的发生中发挥着关键作用。 心脏代谢的后果。 基于社区的观察性队列研究表明 OSA 与 CVD 结局密切相关。 由于 OSA 人群的显着异质性，识别/预测高风险个体一直具有挑战性。 一个可能的解释是呼吸暂停低通气指数 (AHI) 的缺失，该指数是 OSA 诊断和管理的主要指标， 更重要的是，捕捉 OSA 相关低氧血症和睡眠期间自主反应的异质性。 生理变化被认为因年龄、性别和种族而异，因此，表型标记的鉴定表明。 需要更好地量化 OSA 特异性低氧血症和自主反应，以提供改进的事件预测 心脏代谢结果。 在此，我们建议研究两种可以轻松从脉搏血氧饱和度信号中提取的新型生理表型， 睡眠呼吸暂停特定缺氧负担 (“SASHB”) 和对呼吸暂停/呼吸不足的心率反应 (“ΔHR”)。 使用明确的基于大型社区的前瞻性队列研究，包括睡眠心脏健康研究 (SHHS)， 动脉粥样硬化多种族研究 (MESA)、拉丁裔西班牙裔社区健康研究 (HCHS/SOL)、结果 老年男性睡眠障碍 (MrOS)、杰克逊心脏研究 (JHS) 和威斯康星州睡眠队列 (WSC) 追求以下目标 在目标 1 中，我们计划使用个体参与者荟萃分析来研究 SASHB/ΔHR 的效果。 过去的研究已经确定了不同种族/背景的成年人的高血压、糖尿病和心血管疾病的发生率。 研究表明，OSA（通过 AHI 量化）与结果之间的关联强度因年龄、性别和种族而异。 不清楚这一观察结果是由于潜在的生物学差异还是 AHI 无法捕获异质性 在 OSA 中，我们计划测试 SASHB/ΔHR 与糖尿病、高血压、 最后，在目标 2 中，我们计划测试 SASHB/ΔHR 在预测中的附加值。 确定了 10 年 CVD 风险（用于估计动脉粥样硬化性心血管疾病的合并队列方程） 与 AHI 和其他传统 CVD 危险因素进行比较。 总体而言，我们的建议预计将证明 SASHB/ΔHR 与心脏不良代谢的相关性更强 此外，考虑到这些表型可以很容易地预测出来，从而提高整个社区的结果并改善 CVD 风险预测。 这种从家庭睡眠测试设备中提取的个性化医疗方法可能会改变 OSA 的模式 社区评估和管理。