CPAP 治疗延缓阻塞性睡眠呼吸暂停患者的心迷走神经再激活并降低动脉肾素-血管紧张素系统活性。
CPAP Therapy Delays Cardiovagal Reactivation and Decreases Arterial Renin-Angiotensin System Activity in Humans With Obstructive Sleep Apnea.
机构信息
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.
出版信息
J Clin Sleep Med. 2018 Sep 15;14(9):1509-1520. doi: 10.5664/jcsm.7326.
STUDY OBJECTIVES
Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. The effect of OSA treatment with continuous positive airway pressure (CPAP) on the cardiovascular response to a stressor is unknown. We sought to determine the effect of CPAP therapy on heart rate variability (HRV) and arterial stiffness, at baseline, in response to, and recovery from a physiological stressor, Angiotensin II (AngII), in humans with OSA.
METHODS
Twenty-five incident healthy subjects (32% female; 49 ± 2 years) with moderate-severe OSA and nocturnal hypoxia were studied in high-salt balance, a state of maximal renin-angiotensin system (RAS) suppression, before CPAP, and after 4 weeks of effective CPAP therapy (usage > 4 h/night) in a second identical study day. HRV was calculated by spectral power and time domain analysis. Aortic augmentation index (AIx) and carotid-femoral pulse-wave velocity (PWV) were measured by applanation tonometry. HRV and arterial stiffness were measured at baseline and in response to AngII challenge (3 ng/ kg/min·30 minutes, 6 ng/kg/min·30 minutes, recovery·30 minutes). The primary outcome was the association between CPAP treatment and HRV and arterial stiffness responses to, and recovery from, AngII challenge. In an exploratory analysis subjects were stratified by sex.
RESULTS
CPAP corrected OSA and nocturnal hypoxemia. CPAP treatment was associated with increased sensitivity and delayed recovery from AngII (Δln HF [high frequency; recovery: -0.09 ± 0.19 versus -0.59 ± 0.17 ms, = .042; ΔrMSSD [root mean successive differences; recovery: -0.4 ± 2.0 versus -7.2 ± 1.9 ms, = .001], ΔpNN50 [percentage of normal waves differing ≥ 50 ms compared to the preceding wave; AngII: 1.3 ± 2.3 versus -3.0 ± 2.4%, = .043; recovery: -0.4 ± 1.4 versus -6.0 ± 1.9%, = .001], all values pre-CPAP versus post-CPAP treatment). No differences were observed by sex. There was increased AIx sensitivity to AngII after CPAP among men (8.2 ± 1.7 versus 11.9 ± 2.2%, = .046), but not women (11.4 ± 1.5 versus 11.6 ± 2.1%, = .4). No change in PWV sensitivity was observed in either sex.
CONCLUSIONS
CPAP therapy was associated with delayed cardiovagal reactivation after a stressor and down-regulation of the arterial RAS. These findings may have important implications in mitigating cardiovascular risk in both men and women with OSA.
研究目的
阻塞性睡眠呼吸暂停（OSA）与心血管风险增加有关。持续气道正压通气（CPAP）治疗 OSA 对压力反应中心血管的影响尚不清楚。我们旨在确定 CPAP 治疗对心率变异性（HRV）和动脉僵硬的影响，在基线时、对血管紧张素 II（AngII）的反应时和恢复时，在患有 OSA 的健康人中。
方法
在高盐平衡状态下，对 25 名新确诊的患有中重度 OSA 和夜间低氧血症的健康受试者（32%为女性；49±2 岁）进行研究，在 CPAP 之前以及在第二个相同的研究日进行 4 周有效 CPAP 治疗（每晚使用>4 小时）后。通过频谱功率和时域分析计算 HRV。通过平板测压法测量主动脉增强指数（AIx）和颈动脉-股动脉脉搏波速度（PWV）。在基线和 AngII 挑战时（3ng/kg/min·30 分钟，6ng/kg/min·30 分钟，恢复·30 分钟）测量 HRV 和动脉僵硬。主要结局是 CPAP 治疗与 HRV 和动脉僵硬对 AngII 挑战的反应以及从 AngII 挑战中的恢复之间的关系。在一项探索性分析中，根据性别对受试者进行分层。
结果
CPAP 纠正了 OSA 和夜间低氧血症。CPAP 治疗与 AngII 反应的敏感性增加和恢复延迟有关（lnHF[高频；恢复：-0.09±0.19 与-0.59±0.17ms， =.042；rMSSD[根均方差差异；恢复：-0.4±2.0 与-7.2±1.9ms， =.001]，pNN50[与前一个波相比相差≥50ms 的正常波的百分比；AngII：1.3±2.3 与-3.0±2.4%， =.043；恢复：-0.4±1.4 与-6.0±1.9%， =.001]，所有值均为 CPAP 治疗前与 CPAP 治疗后）。按性别观察到没有差异。在男性中，CPAP 治疗后对 AngII 的 AIx 敏感性增加（8.2±1.7 与 11.9±2.2%， =.046），但在女性中没有（11.4±1.5 与 11.6±2.1%， =.4）。在两性中均未观察到 PWV 敏感性的变化。
结论
CPAP 治疗与压力源后心脏迷走神经再激活延迟和动脉肾素-血管紧张素系统（RAS）下调有关。这些发现可能对减轻患有 OSA 的男性和女性的心血管风险具有重要意义。
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