Elucidation of the Influence of Sleep Apnea on Risk of Atrial Fibrillation

描述（由申请人提供）：NHLBI心血管疾病分部2008年战略计划强调了确定制止房颤（AF）流行并降低其相关发病率的策略的必要性。预计到2050年，AF将困扰多达1600万人，每年花费超过67亿美元。房颤目前不能用已知的风险因素来解释，强调需要识别新的触发因素。睡眠呼吸障碍（SDB）在心血管疾病患者中很常见，其伴随的低氧血症和自主神经功能障碍可能会增加AF倾向。因此，SDB可能代表AF预防和治疗策略的新靶点。一个关键的未回答的问题是SDB与AF的关联是否独立于结构性心脏病，或者仅仅是心功能不全的标志物。尽管我们之前的横断面研究显示，SDB相关的AF发生率高2-4倍，但这些报告和其他报告均未包括心脏结构数据或自主神经或生化指标，并且仅讨论了夜间睡眠研究期间发生的心律失常事件。在本申请中，我们将检查阵发性房颤（PAF），这是持续性房颤的早期风险因素，与本申请相关，因为它发生在广泛的心脏电重构和纤维化之前。PAF提供了一个理想的设置，以调查SDB的直接影响，并检查其间歇性的时间模式。我们将对150例PAF患者（来自我们当地的AF诊所）与150例无PAF患者（来自当地心脏病和内科诊所）进行病例对照研究。每组将在重要混杂因素（如年龄（<15岁）、性别、种族和冠心病）方面进行匹配，并使用详细收集的过夜睡眠研究数据、超声心动图测量、生物标志物和1周连续ECG监测进行表征。收集数据的目的是：阐明呼吸事件频率、呼吸暂停亚型（阻塞性与中枢性）和缺氧与PAF相关的程度，与心脏结构异常无关;探索心脏形态、炎症途径、氧化应激和自主神经功能障碍介导SDB-PAF关系的程度，并确定SDB患者AF发作的时间模式是否不同。

DESCRIPTION (provided by applicant): The NHLBI Division of Cardiovascular Diseases 2008 strategic plan has highlighted the need to identify strategies to halt the atrial fibrillation (AF) epidemic and reduce its related morbidity. AF is projected to afflict up to 16 million individuals by the year 2050, costing over $6.7 billion annually. AF is not currently explained by known risk factors, underscoring the need to identify novel triggers. Sleep-disordered breathing (SDB) is common in patients with cardiovascular disease and its attendant hypoxemia and autonomic dysfunction likely enhance AF propensity. Thus, SDB may represent a novel target for AF prevention and treatment strategies. A key, unanswered question is whether the association of SDB to AF is independent of structural heart disease, or merely a marker for cardiac dysfunction. Although our prior cross-sectional work has shown a 2-4 fold higher odds of AF related to SDB, these and other reports have not included cardiac structural data or autonomic or biochemical measures, and have addressed only arrhythmic events occurring during an overnight sleep study. In this application, we will examine paroxysmal AF (PAF), an early stage risk factor for persistent AF, and relevant to this application because it occurs prior to extensive cardiac electrical remodeling and fibrosis. PAF provides an ideal setting to investigate the immediate influences of SDB and examine temporal patterns given its intermittent nature. We will perform a case control study of 150 patients with PAF (from our local AF clinic) matched to 150 patients without PAF (from local cardiology and internal medicine clinics). Each group will be matched on important confounders such as age (15 years), gender, race and coronary heart disease, and characterized using detailed collection of overnight sleep study data, echocardiographic measures, biomarkers and 1-week continuous ECG monitoring. Data will be collected in order to: clarify the extent that respiratory event frequency, apnea subtype (obstructive versus central), and hypoxia are associated with PAF independent of cardiac structural abnormalities; explore the extent to which cardiac morphology, pathways of inflammation, oxidative stress and autonomic dysfunction mediate the SDB-PAF relationship and identify whether temporal patterns of AF paroxysms differ in patients with SDB.