Apnea patterns predict heart disease and mortality

摘要 美国四分之一的死亡是由心血管疾病引起的--庞大的公众 健康负担。阻塞性睡眠呼吸暂停(OSA)是心脏病的一个被低估的危险因素。在OSA， 上呼吸道在睡眠期间反复塌陷，阻碍呼吸。我们发现， 这些呼吸道事件是可遗传的，是心脏病和死亡的风险因素。 我们认为，夜间呼吸紊乱的时间进程是 有关患者阻塞性睡眠呼吸暂停严重程度和患者心脏病长期风险的信息。OSA严重程度为 目前定义为每小时睡眠的平均呼吸事件数(呼吸暂停低通气指数，AHI)。 这个数字忽略了事件持续时间、间隔和关联的生理上的显著变化 不同的睡眠阶段。此外，目前轻度、中度和重度阻塞性睡眠呼吸暂停的临床分界值并不是基于 任何生理机制。因此，我们分析了两个生理信息参数-- 呼吸事件的持续时间及其在夜间的聚集--并发现那些患有短和 经常发生的呼吸道事件死亡的风险最大。事件持续时间是最可遗传的 OSA特征，暗示了该表型的潜在遗传基础。 我们在这个项目中的目标是确定呼吸事件持续时间和事件间变异性 使用通过国家睡眠中心获得的前瞻性数据集预测未来的心血管疾病 研究资源。我们将测试这些新的OSA指标是否预测多个独立队列中的风险 以建立它们的概括性，我们将确定这些指标是否有助于对差异风险进行分层 在男人和女人之间。到目前为止，AHI还没有被证明是女性未来风险的良好预测指标， 然而，对妇女的治疗管理仍然以这一单一数字为指导。更好地识别 根据夜间多导睡眠图中包含的信息对女性的预测有可能 极大地改变了女性阻塞性睡眠呼吸暂停综合征的治疗策略。最后，在横断面研究中，我们将 测试有短时间、有规律发生的呼吸事件的受试者心血管标志物是否升高 风险，基于最先进的心功能和冠状动脉钙化的成像测量。

Abstract One in four deaths in the United States is caused by cardiovascular disease—an enormous public health burden. An under-appreciated risk factor for heart disease is obstructive sleep apnea (OSA). In OSA, the upper airway collapses repeatedly during sleep and prevents breathing. We have found that the duration of these respiratory events is heritable and is a risk factor for heart disease and death. We believe that the time course of breathing disturbances through the night is a rich source of information about a patient's OSA severity and the patient's long term risk for heart disease. OSA severity is currently defined by the mean number of respiratory events per hour asleep (apnea-hypopnea index, AHI). This number ignores physiologically significant variation in event duration, their spacing, and association with different sleep stages. Moreover, current clinical cutoffs for mild, moderate, and severe OSA are not based on any physiological mechanism. We have therefore analyzed two physiologically informative parameters—the duration of respiratory events and their clustering within the night—and have found that those with short and regularly occurring respiratory events are at the greatest risk of dying. Event duration is the most heritable of OSA traits, suggesting a potential genetic underpinning to this phenotype. Our goals in this project are to determine how respiratory event duration and inter-event variability predict future cardiovascular disease using prospective data sets available through the National Sleep Research Resource. We will test whether these novel OSA metrics predict risk in multiple independent cohorts to establish their generalizability, and we will determine whether these metrics help stratify differential risk between men and women. To date, the AHI has not been shown to be a good predictor of future risk in women, yet therapeutic management for women continues to be guided by this single number. Identifying better predictors for women from the information contained in the night-time polysomnogram has the potential to dramatically change the therapeutic strategies for women with OSA. Finally, in cross-sectional studies, we will test whether subjects with short regularly occurring respiratory events have elevated markers of cardiovascular risk, based on state-of-the-art imaging measures of cardiac function and coronary artery calcification.