Apnea patterns predict heart disease and mortality

摘要 在美国，四分之一的死亡是由心血管疾病引起的， 健康负担。心脏病的一个未被充分认识的危险因素是阻塞性睡眠呼吸暂停（OSA）。在OSA中， 上呼吸道在睡眠期间反复塌陷并阻止呼吸。我们发现， 这些呼吸系统疾病是可遗传的，是心脏病和死亡的危险因素。 我们认为，夜间呼吸紊乱的时间进程是一个丰富的来源， 关于患者的OSA严重性和患者的心脏病的长期风险的信息。OSA严重程度为 目前定义为每小时睡眠呼吸事件的平均数（呼吸暂停低通气指数，AHI）。 这个数字忽略了事件持续时间、事件间隔以及与 不同的睡眠阶段此外，目前轻度、中度和重度OSA的临床临界值并不基于 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，并发现那些短， 经常发生的呼吸道疾病死亡的风险最大。事件持续时间是最易遗传的 OSA性状，表明这种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 使用国家睡眠管理局提供的前瞻性数据集预测未来的心血管疾病 研究资源。我们将在多个独立队列中测试这些新的OSA指标是否能预测风险 以建立其普遍性，我们将确定这些指标是否有助于对差异风险进行分层 男人和女人之间。迄今为止，AHI尚未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。识别更好 从夜间多导睡眠图中包含的信息中预测女性的可能性， 极大地改变了女性阻塞性睡眠呼吸暂停综合症的治疗策略。最后，在横向研究中，我们将 测试具有短的规律发生的呼吸事件的受试者是否具有升高的心血管标志物 风险，基于心脏功能和冠状动脉钙化的最新成像测量。

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.