Sex differences in obstructive sleep apnea phenotypes, the multi-ethnic study of atherosclerosis
Sex differences in obstructive sleep apnea phenotypes, the multi-ethnic study of atherosclerosis
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DOI：
10.1093/sleep/zsz274
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发表时间：
2020-05-01
期刊：
影响因子：
5.6
通讯作者：
Redline, Susan
中科院分区：
文献类型：
--
作者：
Won, Christine H. J.;Reid, Michelle;Redline, Susan
研究目的：阻塞性睡眠呼吸暂停（OSA）性别差异的基础尚不清楚。我们量化了事件定义、睡眠状态和体位对男性和女性呼吸暂停低通气指数（AHIs）的影响，并评估了病理生理内型的性别差异。方法：分析来自多民族动脉粥样硬化研究的2057名参与者的多导睡眠图（PSG）数据。采用不同的去饱和和觉醒标准对不同的AHIs进行比较。通过对PSG信号的逐呼吸分析得出内窥镜类型（环路增益、气道湿陷性、唤醒阈值）。回归模型估计了内型在多大程度上解释了AHI的性别差异。结果：样本（平均68.5±9.2岁）包括54%的女性。OSA （AHI4P >= 15/h，以去饱和度=4%为定义）在41.1%的男性和21.8%的女性中发现。与AHI4P相比，当使用3%的去饱和和/或觉醒标准时，男性/女性AHI比率下降了5%-10%；P < 0.05。无论事件去饱和标准如何，REM-OSA （REM-AHI >= 15/h）在男性和女性中相似。REM-AHI4P >= 15/h的男性和女性各占57%。NREM期男性AHI4P为女性的2.49 （CI95: 2.25, 2.76）。女性在NREM中表现出较低的环路增益，较少的气道可折叠性和较低的唤醒阈值（ps < 0.0005）。内型解释了NREM-AHI4P中30%的相对性别差异。结论：NREM-AHI水平和生理内型存在显著的性别差异。生理内型解释了NREM-AHI相对性别差异的重要部分。使用4%去饱和标准的定义低估了女性的AHI。结合非快速眼动和快速眼动事件，模糊了女性快速眼动中的OSA患病率。本研究首次量化了男性和女性的去饱和、觉醒、睡眠状态和体位对呼吸暂停-低通气指数（AHI）的影响，并在一个大的、不同的人群中评估阻塞性睡眠呼吸暂停（OSA）生理内型的性别差异。我们的研究结果表明，阻塞性睡眠呼吸暂停的性别差异受到状态特异性机制的影响，这反映在气道可折叠性、循环增益和唤醒阈值的多导睡眠图估计中。非快速眼动睡眠期间的保护机制并不能实质性地保护女性在快速眼动睡眠期间免于气道塌陷。鉴于越来越多的证据表明REM-OSA与不良心血管结局之间存在关联，女性相对较高的REM-AHI具有临床意义。由于目前的指南没有直接针对REM-AHI进行治疗，我们的数据表明，基于总AHI（主要反映NREM-AHI），女性可能不成比例地接受OSA治疗不足。
Study Objectives: The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea-hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes.Methods: Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI.Results: The sample (mean 68.5 +/- 9.2 years) included 54% women. OSA (AHI4P >= 15/h, defined by events with =4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%-10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI >= 15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P >= 15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P.Conclusions: There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.Statement of SignificanceThis is the first study to quantify the influences of desaturations, arousals, sleep-state, and position on apnea-hypopnea index (AHI) in men and women, and to evaluate sex differences in obstructive sleep apnea (OSA) physiological endotypes in a large, diverse population. Our results suggest that sex differences in OSA are influenced by state-specific mechanisms that are reflected by polysomnographic estimates of airway collapsibility, loop gain, and arousal threshold. Protective mechanisms during NREM sleep do not substantively protect women from airway collapse during REM sleep. The relatively high REM-AHI in women is of clinical significance given growing evidence of the association between REM-OSA and adverse cardiovascular outcomes. Since current guidelines do not directly address REM-AHI for treatment, our data suggest women may be disproportionately under-treated for OSA based on the total AHI, which predominantly reflects NREM-AHI.