持续气道正压通气对心血管生物标志物的影响：睡眠呼吸暂停应激随机对照试验
Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial.
作者信息
Paz Y Mar Hugo L, Hazen Stanley L, Tracy Russell P, Strohl Kingman P, Auckley Dennis, Bena James, Wang Lu, Walia Harneet K, Patel Sanjay R, Mehra Reena
机构信息
Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH.
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
出版信息
Chest. 2016 Jul;150(1):80-90. doi: 10.1016/j.chest.2016.03.002. Epub 2016 Mar 18.
BACKGROUND
Although existing research highlights the relationship of OSA and cardiovascular disease, the effect of OSA treatment on cardiovascular biomarkers remains unclear. We evaluated the effect of OSA treatment on oxidative stress/inflammation measures.
METHODS
We conducted a parallel, randomized controlled trial in moderate to severe OSA (apnea-hypopnea index ≥ 15) patients to examine effects of 2-month CPAP vs sham-CPAP on the primary outcome of oxidative stress/inflammation (F2-isoprostanes: ng/mg) and myeloperoxidase: pmol/L) and secondary oxidative stress measures. Exploratory secondary analyses included vascular and systemic inflammation markers. Linear models adjusted for baseline values examined effect of CPAP on biomarker change (least squares means, 95% CI) including secondary stratified analyses examining CPAP adherence and degree of hypoxia.
RESULTS
Of 153 participants, 76 were randomized to CPAP and 77 to sham-CPAP. In an intent-to-treat analyses, no significant change was observed in the sham and CPAP groups respectively: F2-isoprostanes (-0.02 [-0.12 to 0.10] vs -0.08 [-0.18 to 0.03]) or myeloperoxidase (-3.33 [-17.02 to 10.37] vs -5.15 [-18.65 to 8.35]), nor other oxidative markers; findings that persisted in analyses stratified by adherence and hypoxia. Exploratory analyses revealed percentage reduction of soluble IL-6 receptor (ng/mL) levels (-0.04 [-0.08 to -0.01] vs 0.02 [-0.02 to 0.06], P = .019) and augmentation index (%) (-6.49 [-9.32 to -3.65] vs 0.44 [-2.22 to 3.10], P < .001) with CPAP compared with sham, respectively.
CONCLUSIONS
In moderate to severe OSA, 2-month CPAP vs sham did not reduce oxidative stress despite consideration of a broad range of measures, positive airway pressure adherence, and hypoxia burden. These findings suggest that nonoxidative stress pathways primarily modulate OSA-related cardiovascular consequences.
TRIAL REGISTRATION
ClinicalTrials.govNCT00607893.
背景
尽管现有研究强调了阻塞性睡眠呼吸暂停（OSA）与心血管疾病的关系，但OSA治疗对心血管生物标志物的影响仍不明确。我们评估了OSA治疗对氧化应激/炎症指标的影响。
方法
我们对中度至重度OSA（呼吸暂停低通气指数≥15）患者进行了一项平行随机对照试验，以研究2个月持续气道正压通气（CPAP）与假CPAP对氧化应激/炎症的主要结局指标（F2-异前列腺素：纳克/毫克）和髓过氧化物酶：皮摩尔/升）以及次要氧化应激指标的影响。探索性二次分析包括血管和全身炎症标志物。针对基线值进行调整的线性模型检查了CPAP对生物标志物变化的影响（最小二乘均值，95%置信区间），包括检查CPAP依从性和低氧程度的二次分层分析。
结果
153名参与者中，76人被随机分配至CPAP组，77人被随机分配至假CPAP组。在意向性分析中，假CPAP组和CPAP组在F2-异前列腺素（-0.02[-0.12至0.10]对-0.08[-0.18至0.03]）或髓过氧化物酶（-3.33[-17.02至10.37]对-5.15[-18.65至8.35]）方面均未观察到显著变化，其他氧化标志物也未观察到显著变化；这些结果在按依从性和低氧分层的分析中持续存在。探索性分析显示，与假CPAP相比，CPAP治疗后可溶性白细胞介素-6受体（纳克/毫升）水平降低百分比（-0.04[-0.08至-从0.01]对0.02[-0.02至0.06]，P = 0.019）和增强指数（%）（-6.49[-9.32至-3.65]对0.44[-2.22至3.10]，P < 0.001）。
结论
在中度至重度OSA患者中，尽管考虑了广泛指标、气道正压通气依从性和低氧负担，但2个月的CPAP治疗与假CPAP治疗相比并未降低氧化应激。这些结果表明，非氧化应激途径主要调节与OSA相关的心血管后果。
试验注册
ClinicalTrials.govNCT00607893 。
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