Azarbarzin Ali, Vena Daniel, Esmaeili Neda, Wellman Andrew, Pinilla Lucía, Messineo Ludovico, Zinchuk Andrey, Alex Raichel, Baumert Mathias, Loffler Kelly A, Anderson Craig S, White David P, Redline Susan, Gottlieb Daniel J, Barbé Ferran, Peker Yuksel, Sánchez-de-la-Torre Manuel, McEvoy Doug, Sands Scott A
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA.
Flinders Health and Medical Research Institute: Sleep Health, College of Medicine and Public Health, Flinders University, Level 2, Building A, Mark Oliphant Building, 5 Laffer Drive, Bedford Park, South Australia 5042, Australia.
Eur Heart J. 2025 Aug 5. doi: 10.1093/eurheartj/ehaf447.
Randomized trials of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in patients with cardiovascular disease have not detected reduced risk of major adverse cardiovascular and cerebrovascular events (MACCEs). This study tested whether the cardiovascular benefit of CPAP occurs preferentially in high-risk OSA, characterized by greater OSA-related heart rate acceleration or hypoxaemia.
In a post hoc analysis of pooled Randomized Intervention with Continuous Positive Airway Pressure in Coronary Artery Disease and Obstructive Sleep Apnoea, Impact of Continuous Positive Airway Pressure on Patients with Acute Coronary Syndrome and Nonsleepy Obstructive Sleep Apnoea, and Sleep Apnoea Cardiovascular Endpoints Study randomized trials; outcomes were stratified by high-risk OSA status, defined by heart rate response following OSA respiratory events >9.4 b.p.m. (third tertile) or oxygen desaturation area under baseline (hypoxic burden) > 87.1% min/h (third tertile). Cox mixed models quantified the CPAP treatment effect on MACCE (including cardiovascular mortality, myocardial infarction, and stroke) within high-risk OSA and the difference vs low-risk status (primary test). Secondary analyses examined participants without excessive sleepiness (Epworth <11 points) or without increased blood pressure (systolic/diastolic <140/90 mmHg).
In 3549 participants, 16.6% and 16.3% reached the MACCE endpoint with CPAP (n = 1778) and usual care (n = 1771), respectively. The CPAP treatment effect was greater in participants with vs without high-risk OSA [interaction hazard ratio (iHR) .69, 95% confidence interval (CI) .50-.95, Pinteraction = .024; Nhigh-risk = 1832]. The differential effect was stronger in those without excessive sleepiness (iHR .59, 95% CI .41-.84; Nhigh-risk = 1509), or without increased blood pressure (iHR .54, 95% CI .36-.81; Nhigh-risk = 1244). Continuous positive airway pressure benefits in high-risk OSA were observed alongside harm in low-risk OSA.
Continuous positive airway pressure preferentially improves cardiovascular outcomes in high-risk OSA, while harm in low-risk OSA may counteract this effect. These findings provide a pathway to identify patients likely to benefit.
针对心血管疾病患者阻塞性睡眠呼吸暂停（OSA）进行持续气道正压通气（CPAP）治疗的随机试验未发现主要不良心血管和脑血管事件（MACCE）风险降低。本研究旨在测试CPAP对心血管的益处是否优先出现在以OSA相关心率加速或低氧血症更严重为特征的高危OSA患者中。
在对冠状动脉疾病与阻塞性睡眠呼吸暂停持续气道正压通气随机干预、持续气道正压通气对急性冠状动脉综合征和无嗜睡性阻塞性睡眠呼吸暂停患者的影响以及睡眠呼吸暂停心血管终点研究等随机试验进行的事后分析中；根据高危OSA状态进行分层，高危OSA状态定义为OSA呼吸事件后心率反应>9.4次/分钟（第三三分位数）或基线以下氧饱和度下降面积（缺氧负荷）>87.1%分钟/小时（第三三分位数）。Cox混合模型量化了CPAP治疗对高危OSA患者MACCE（包括心血管死亡率、心肌梗死和中风）的治疗效果以及与低危状态相比的差异（主要测试）。次要分析检查了没有过度嗜睡（Epworth评分<11分）或血压未升高（收缩压/舒张压<140/90mmHg）的参与者。
在3549名参与者中，接受CPAP治疗的患者（n = 1778）和接受常规治疗的患者（n = 1771）分别有16.6%和16.3%达到MACCE终点。与无高危OSA的参与者相比，CPAP对有高危OSA的参与者治疗效果更大[交互风险比（iHR）0.69，95%置信区间（CI）0.50 - 0.95，P交互作用 = 0.024；高危n = 1832]。在没有过度嗜睡的参与者中（iHR 0.59，95% CI 0.41 - 0.84；高危n = 1509）或血压未升高的参与者中（iHR 0.54，95% CI 0.36 - 0.81；高危n = 1244），这种差异效应更强。在高危OSA患者中观察到持续气道正压通气有益，而在低危OSA患者中则有不良影响。
持续气道正压通气优先改善高危OSA患者的心血管结局，而低危OSA患者中的不良影响可能抵消这种效果。这些发现为识别可能受益的患者提供了一条途径。
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