Koç University School of Medicine, Istanbul, Turkey; University of Gothenburg, Gothenburg, Sweden; Brigham & Women's Hospital, Boston, MA, USA; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Lund University, Lund, Sweden.
Koç University School of Medicine, Istanbul, Turkey; Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
EBioMedicine. 2024 Mar;101:105015. doi: 10.1016/j.ebiom.2024.105015. Epub 2024 Feb 24.
Continuous positive airway pressure (CPAP) has failed to reduce cardiovascular risk in obstructive sleep apnoea (OSA) in randomized trials. CPAP increases angiopoietin-2, a lung distension-responsive endothelial proinflammatory marker associated with increased cardiovascular risk. We investigated whether CPAP has unanticipated proinflammatory effects in patients with OSA and cardiovascular disease.
Patients with OSA (apnoea-hypopnea index [AHI] ≥15 events/h without excessive sleepiness) in the Randomized Intervention with CPAP in Coronary Artery Disease and OSA study were randomized to CPAP or usual care following coronary revascularization. Changes in plasma levels of biomarkers of endothelial (angiopoietin-2, Tie-2, E-selectin, vascular endothelial growth factor [VEGF-A]) and lung epithelial (soluble receptor of advanced glycation end-products [sRAGE]) function from baseline to 12-month follow-up were compared across groups and associations with cardiovascular morbidity and mortality assessed.
Patients with OSA (n = 189; 84% men; age 66 ± 8 years, BMI 28 ± 3.5 kg/m, AHI 41 ± 23 events/h) and 91 patients without OSA participated. Angiopoietin-2 remained elevated whereas VEGF-A declined significantly over 12 months in the CPAP group (n = 91). In contrast, angiopoietin-2 significantly declined whereas VEGF-A remained elevated in the usual care (n = 98) and OSA-free groups. The changes in angiopoietin-2 and VEGF-A were significantly different between CPAP and usual care, whereas Tie-2, sRAGE and E-selectin were similar. Greater 12-month levels of angiopoietin-2 were associated with greater mortality. Greater CPAP levels were associated with worse cardiovascular outcomes.
Greater CPAP levels increase proinflammatory, lung distension-responsive angiopoietin-2 and reduce cardioprotective angiogenic factor VEGF-A compared to usual care, which may counteract the expected cardiovascular benefits of treating OSA.
National Institutes of Health/National Heart, Lung, and Blood Institute; Swedish Research Council; Swedish Heart-Lung Foundation; ResMed Foundation.
在随机试验中，持续气道正压通气（CPAP）未能降低阻塞性睡眠呼吸暂停（OSA）的心血管风险。CPAP 会增加血管生成素-2，这是一种与心血管风险增加相关的肺扩张反应性内皮前炎症标志物。我们研究了 CPAP 是否对 OSA 和心血管疾病患者有意外的促炎作用。
随机干预 CPAP 对冠状动脉疾病和 OSA 研究中的 OSA 患者（呼吸暂停低通气指数[AHI]≥15 次/小时但无过度嗜睡）在冠状动脉血运重建后被随机分配至 CPAP 或常规护理。从基线到 12 个月随访，比较各组之间血浆内皮（血管生成素-2、Tie-2、E-选择素、血管内皮生长因子[VEGF-A]）和肺上皮（可溶性晚期糖基化终产物受体[sRAGE]）功能生物标志物水平的变化，并评估其与心血管发病率和死亡率的关系。
189 例 OSA 患者（84%为男性；年龄 66±8 岁，BMI 28±3.5kg/m，AHI 41±23 次/小时）和 91 例无 OSA 患者参与了这项研究。CPAP 组（n=91）中，血管生成素-2 在 12 个月内持续升高，而 VEGF-A 显著下降。相反，在常规护理（n=98）和无 OSA 组中，血管生成素-2 显著下降，而 VEGF-A 保持升高。CPAP 组与常规护理组相比，血管生成素-2 和 VEGF-A 的变化明显不同，而 Tie-2、sRAGE 和 E-选择素则相似。12 个月时较高的血管生成素-2 水平与较高的死亡率相关。CPAP 水平越高，心血管结局越差。
与常规护理相比，较高的 CPAP 水平会增加促炎、肺扩张反应性的血管生成素-2，并降低保护性血管生成因子 VEGF-A，这可能会抵消治疗 OSA 的预期心血管益处。
美国国立卫生研究院/美国国家心肺血液研究所；瑞典研究委员会；瑞典心肺基金会；瑞思迈基金会。
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