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

描述（由申请人提供）：本研究旨在探讨心脏自主神经控制在不同睡眠阶段睡眠呼吸障碍（SDB）中的重要作用，研究对象为700名公立小学（K-5）儿童。该队列最初是根据nhlbi资助的一项名为“儿童睡眠呼吸障碍患病率（R01- hl -63772-05）”的R01研究建立的。最初研究的目的是评估儿童SDB的患病率并确定相关因素。其中一个主要发现是收缩压与SDB显著相关，独立于BMI。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测试。收集了大量关于SDB、呼吸暂停发作、睡眠质量和睡眠阶段的数据。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心电图数据。我们建议对这些心电图数据进行处理和分析，这是原研究中没有的新任务。我们将推导心率变异性（HRV）指数的时域和频域测量作为心脏自主控制的测量。具体来说，我们将计算总的9小时HRV，特定睡眠阶段的5分钟HRV，以及呼吸暂停发作前后的5分钟HRV。HRV指数将与广泛且已有的SDB数据一起进行分析，以探讨以下研究问题：(1)SDB是否与HRV谱差有关，表明心脏自主控制受损；(2) SDB程度与HRV损害是否存在剂量反应关系；(3) BMI是否对上述SDB和HRV相关性有影响；(4) HRV测量的自主控制受损能否解释SDB与儿童血压升高的关系；(5)睡眠呼吸暂停发作是否会立即损害心脏自主神经平衡；(6)儿童睡眠阶段（REM、非REM和清醒阶段）与心脏自主神经控制的定量关系是什么，SDB是否对这种关系有负面影响？这项横断面研究是基于我们之前在心脏自主控制、儿童和成人SDB以及代谢紊乱方面的广泛工作。它高度响应了最近的RFA（项目公告编号：PA-06-238，“睡眠和睡眠障碍研究（R21）”）。分析这些心脏自主控制数据，结合原始研究的大量睡眠数据，将使我们能够确定我们是否可以成功地将传统的睡眠障碍研究扩展到心脏风险评估中，这已经成为心脏病学中一个独特而成熟的研究和应用。该项目还将使我们能够验证一个新的研究假设，即SDB与心血管疾病的高风险相关，部分原因是其对副交感神经损伤和交感神经过度激活的心脏自主控制产生负面影响。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最严重的形式。这个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验证一个新的研究假设-儿童SDB与心脏风险较高相关，部分原因是其对副交感神经损伤和交感神经过度激活的心脏自主控制产生负面影响，从而导致致命性心律失常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.