Sleep-disordered breathing, sleep stages, and heart rate variability in children

描述（由申请人提供）：本研究的目的是探索心脏自主神经控制在不同睡眠阶段的睡眠呼吸障碍（SDB）中的重要作用，该研究在公立小学（K-5）随机产生的700名儿童中进行。该队列最初是根据NHLBI资助的R 01研究建立的，该研究题为“儿童睡眠呼吸障碍的患病率”（R 01-HL-63772-05）。“最初研究的目的是评估儿童SDB的患病率，并确定相关因素。主要发现之一是收缩压与SDB显著相关，与BMI无关。基线检查包括标准化的夜间睡眠实验室研究、全面的睡眠史、体格检查和评估心理和认知功能的心理测量电池。收集了关于SDB、呼吸暂停发作、睡眠质量和睡眠阶段的大量数据。作为基线标准9小时多导睡眠图的“副产品”，还记录并存储了单通道连续EKG数据。我们建议处理和分析这些心电图数据，这是一个新的任务，不包括在原来的研究。我们将推导出心率变异性（HRV）指标的时域和频域测量值，作为心脏自主控制的测量值。具体而言，我们将计算总体9小时HRV、睡眠阶段特定5分钟HRV以及呼吸暂停发作前后的5分钟HRV。本研究将结合大量的SDB数据对HRV指标进行分析，以探讨以下研究问题：（1）SDB是否与心率变异性差相关，提示心脏自主控制功能受损;（2）SDB程度与HRV受损之间是否存在剂量反应关系;（3）BMI对上述SDB与HRV相关性是否存在效应修正;（4）心率变异性（HRV）测定的自主神经控制功能受损是否解释了SDB与儿童血压升高的关系：（5）睡眠呼吸暂停发作是否导致心脏自主神经平衡立即受损;（6）睡眠阶段之间的定量关系是什么睡眠呼吸暂停是否对儿童的快速眼动、非快速眼动和清醒期与心脏自主控制的关系产生负面影响？这项横断面研究是基于我们以前对心脏自主控制、儿童和成人SDB以及代谢紊乱的广泛研究。它对最近的RFA（计划公告编号：PA-06-238，“睡眠和睡眠障碍研究（R21）。“结合原始研究的大量睡眠数据分析这些心脏自主控制数据，将使我们能够确定我们是否可以成功地将我们传统的睡眠障碍研究扩展到心脏风险评估中，这已经发展成为心脏病学中独特而成熟的研究和应用。该项目还将使我们能够测试一个新的研究假设-SDB与较高的心血管疾病风险相关，部分原因是其对心脏自主控制对副交感神经损伤和交感神经过度激活的负面影响。大约20-28%的学龄儿童患有SDB，1-3%的学龄儿童患有阻塞性睡眠呼吸暂停，这是SDB的最严重形式。该项目将使我们能够成功地将传统的睡眠障碍研究扩展到心脏风险评估。该项目还将使我们能够测试一个新的研究假设-儿童SDB与较高的心脏风险相关，部分原因是其对心脏自主控制的负面影响，对副交感神经损伤和交感神经过度激活，这可能导致致命性心律失常的阈值降低和血压升高。从这项研究中获得的知识可能会改善儿童SDB的管理和治疗。

DESCRIPTION (provided by applicant): The purpose of this study is to explore the significant roles of cardiac autonomic control in sleep-disordered breathing (SDB) during various sleep stages in an established cohort of 700 children randomly generated from public elementary schools (K-5). The cohort was originally established from an NHLBI-funded R01 study entitled "Prevalence of Sleep-Disordered Breathing in Children (R01-HL-63772-05)." The objectives of the original study were to evaluate the prevalence of childhood SDB and to identify correlates. One of the major findings was that systolic blood pressure was significantly associated with SDB independent of BMI. The baseline examinations included a standardized overnight sleep laboratory study, comprehensive sleep history, physical examination and a psychometric battery that assesses psychological and cognitive functions. Extensive data on SDB, episodes of apnea, sleep quality, and sleep stages were collected. As a "by-product" of the baseline standard 9-hour polysomnogram, a single channel of continuous EKG data were also recorded and stored. We propose to process and analyze these EKG data, which is a new task not included in the original study. We will derive time and frequency domain measures of heart rate variability (HRV) indices as measures of cardiac autonomic control. Specifically, we will calculate overall 9-hour HRV, sleep stage specific 5-minute HRV, and before and after apnea episode 5-minute HRV. The HRV indices will be analyzed together with the extensive and already available SDB data to examine the following research questions: (1) Whether SDB is associated with poor HRV profiles, indicating impairment of cardiac autonomic control; (2) Whether there is a dose response relationship between the degree of SDB and HRV impairment; (3) Whether there is an effect modification by BMI on the above SDB and HRV associations; (4) Whether impaired autonomic control as measured by HRV explains the relationship between SDB and elevated blood pressure in children; (5) Whether an episode of sleep apnea leads to immediate impairment of cardiac autonomic balance; and (6) What is the quantitative relationship between sleep stages (REM, nonREM, and wake stages) and cardiac autonomic control in children, and whether SDB has a negative impact on such relationship? This proposed cross-sectional study is based on our previous extensive works on cardiac autonomic control, SDB in children and adults, and metabolic disorders. It is highly responsive to a recent RFA (Program Announcement Number: PA-06-238, "Research on Sleep and Sleep Disorders (R21)." Analysis of these cardiac autonomic control data in combination with extensive sleep data from the original study will enable us to determine whether we can successfully extend our traditional sleep disorder study in cardiac risk assessment, which has grown into a distinctive and matured research and application in cardiology. This project will also enable us to test a novel research hypothesis - that SDB is associated with higher cardiovascular disease risk partially by its negative impact on cardiac autonomic control towards parasympathetic impairment and sympathetic over-activation. About 20-28% school-aged children have SDB, and 1-3% school-aged children have obstructive sleep apnea, the most severe form of SDB. This project will enable us to successfully extend our traditional sleep disorder study into cardiac risk assessment. This project will also enable us to test a novel research hypothesis - that SDB in children is associated with higher cardiac risk partially by its negative impact on cardiac autonomic control towards parasympathetic impairment and sympathetic over-activation, which can lead to decreased threshold for fatal arrhythmias and elevated blood pressure. The knowledge gained from this study can potentially improve the management and treatment of childhood SDB.