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

说明(由申请人提供)：NHLBI心血管病科2008年战略计划强调需要确定遏制房颤(房颤)流行和降低其相关发病率的战略。预计到2050年，房颤患者将达到1600万人，每年造成的损失超过67亿美元。房颤目前还没有被已知的危险因素所解释，这强调了识别新的触发因素的必要性。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房颤的倾向。因此，SDB可能成为房颤防治策略的新靶点。一个关键的悬而未决的问题是，SDB与房颤的关联是独立于结构性心脏病，还是仅仅是心脏功能障碍的标志。尽管我们之前的横断面研究表明，与SDB相关的房颤的几率增加了2-4倍，但这些报告和其他报告没有包括心脏结构数据或自主或生化指标，只涉及夜间睡眠研究中发生的心律失常事件。在这项应用中，我们将检查阵发性房颤(PAF)，这是持续性房颤的早期危险因素，与这项应用相关，因为它发生在广泛的心脏电重构和纤维化之前。考虑到SDB的间歇性，PAF为研究SDB的直接影响和检查时间模式提供了理想的环境。我们将对150名PAF患者(来自我们当地的房颤诊所)和150名没有PAF的患者(来自当地的心脏病和内科诊所)进行病例对照研究。每组都将在年龄(15岁)、性别、种族和冠心病等重要混杂因素上进行匹配，并通过详细收集过夜睡眠研究数据、超声心动图测量、生物标记物和一周连续心电监测来确定特征。收集数据的目的是：明确呼吸事件频率、呼吸暂停亚型(阻塞性与中枢性)和低氧与PAF的相关性，独立于心脏结构异常；探索心脏形态、炎症途径、氧化应激和自主神经功能障碍在多大程度上调节SDB-PAF的关系，并确定SDB患者房颤发作的时间模式是否有所不同。

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.