CPAP可降低肥胖的呼吸暂停成人的血压

Dr. Julio A. Chirinos

《新英格兰医学杂志》6月11日在线发表的两项研究显示，在肥胖的中至重度阻塞性睡眠呼吸暂停患者中，持续气道正压通气（CPAP）可轻微降低血压。相比之下，一项研究中使用的补氧和另一项研究中的减重（约7 kg）均对血压无有益影响。

第1项研究由退伍军人事务部波士顿医疗系统的Daniel J. Gottlieb医生及其同事进行，旨在比较CPAP与夜间补氧对一些心血管风险标志物（包括血压）的影响。这项多中心研究入选确诊冠心病或具有多个心血管危险因素的患者或在筛查阻塞性睡眠呼吸暂停时被检出合并该病的心脏病患者（45~75岁）。

318例患者被随机等分成3组。第1组接受CPAP+有关健康生活方式和睡眠方式的教育，第2组接受夜间插管补氧+生活方式和睡眠教育，第3组接受单纯睡眠教育（对照组）。治疗时间为12周。CPAP组、补氧组和对照组的平均体重指数分别为33.0 kg/m²、34.7 kg/m²和 33.7 kg/m²，平均呼吸暂停低通气指数评分分别为25.4、24.0和25.5次事件/小时。

研究结束时，CPAP组的24小时平均动脉血压（87.8 mm Hg）显著低于补氧组（90.2 mm Hg）和对照组（89.0 mm Hg）。研究者表示，虽然差异“轻微”，但这与“心血管风险有意义的降低”相关。在血压已被抗高血压药较好控制的患者和对CPAP依从性仅“一般”的患者中也观察到这一获益。

相比之下，补氧组和对照组患者的平均动脉血压无显著差异，尽管补氧确实可降低夜间低氧血症并且患者对氧疗的依从性明显高于对CPAP的依从性。校正患者年龄、性别、人种、体重指数和抗高血压药类型等潜在混杂因素后进行进一步分析，未发现结果发生明显改变。

研究者表示，该研究不支持临床上常见的但在很大程度上未经过检验的使用补氧对不适用CPAP的阻塞性睡眠呼吸暂停患者进行补救治疗的做法（N. Engl. J. Med. 2014;370:2276-85 [doi: 10.1056/NEJMoa1306766]）。

第2项研究由费城退伍军人事务部医学中心的Julio A. Chirinos医生及其同事进行，目的是在C反应蛋白水平升高的中至重度阻塞性睡眠呼吸暂停肥胖成人中比较24周单纯CPAP、单纯减重和CPAP+减重的效果。共181例患者接受随机分组，但仅136例完成研究：CPAP组48例，减重组42组，联合干预组46例。

干预结束时，单纯减重组的减重程度（6.8 kg）与联合干预组（7.0 kg）相似，而单纯CPAP组无变化。

该研究的主要终点为C反应蛋白水平改善。3个研究组在这一终点方面无显著差异。然而，与单纯减重组（–6.8 mm Hg）和单纯CPAP组（–3.0 mm Hg）相比，联合干预组达到收缩压显著降低（–14.1 mm Hg）这一次要终点。此外，联合干预组胰岛素抵抗和血清甘油三酯水平也出现改善（N. Engl. J. Med. 2014;370:2265-75 [doi: 10.1056/NEJMoa1306187]）。研究者表示，作为用于改善阻塞性睡眠呼吸暂停肥胖患者的心血管风险的策略的一个重要部分，减重干预是有效的。

第1项研究由国立心肺和血液研究所（NHLBI）和国立研究资源中心支持。研究中所用的设备由飞利浦伟康公司提供。Gottlieb医生与飞利浦伟康和瑞思迈公司存在联系，其同事与多家药企存在联系。

第2项研究也由NHLBI支持。研究中所用的CPAP设备由瑞思迈公司无偿提供，但该公司不参与研究设计、数据采集和分析及稿件撰写。Chirinos医生声明无经济利益冲突，其同事与勃林格殷格翰等多家公司存在联系。

随刊述评

提倡减重联合CPAP使用

纽约哥伦比亚大学的Robert C. Basner医生表示，这两项研究为临床医生提供了两个值得考虑的重要信息。第一，CPAP可改善高危肥胖患者的高血压并降低其心血管风险，即使他们已接受降压治疗并且没有日间嗜睡这一阻塞性睡眠呼吸暂停的常见特征。第二，在进行CPAP治疗的同时实施减重干预可进一步降低心血管风险。

然而，由于第1项研究中的夜间CPAP使用率较低（依从性差）及由于第2项研究中的C反应蛋白值的变异性较大且对这些值采取了不常见的统计学处理，因此限制了对这些研究结果的进一步解读。

Basner医生是第2项研究的数据和安全监测委员会的成员（(N. Engl. J. Med. 2014;370:2339-41 [doi: 10.1056/NEJMe1404501]）。

By: MARY ANN MOON, Internal Medicine News

 

The use of continuous positive airway pressure modestly reduced blood pressure in two separate studies involving obese patients who had moderate to severe obstructive sleep apnea, according to reports published online June 11 in the New England Journal of Medicine.

In contrast, neither the use of supplemental oxygen in one study nor a weight loss of approximately 7 kg in the other study had a beneficial effect on blood pressure.

In the first study, investigators compared the effects of CPAP against those of nocturnal supplemental oxygen on several markers of cardiovascular risk, including blood pressure. The multicenter study involved cardiology patients aged 45-75 years who either had established coronary heart disease or multiple cardiovascular risk factors, and who also were found to have obstructive sleep apnea when screened for the disorder.

The 318 patients were randomly assigned in equal numbers to receive CPAP plus education in healthy lifestyle and sleep practices, nocturnal supplemental oxygen delivered via cannula plus lifestyle and sleep education, or lifestyle and sleep education alone (the control group) for 12 weeks, said Dr. Daniel J. Gottlieb, of the Veterans Affairs Boston Healthcare System, and his associates.

At the end of the study, 24-hour mean arterial blood pressure was significantly lower among patients in the CPAP group (87.8 mm Hg) than with oxygen (90.2 mm Hg) or education alone (89.0 mm Hg), a "modest" difference in magnitude that nevertheless has been associated with "a meaningful reduction in cardiovascular risk," the investigators noted.The mean body mass index was 33.0 kg/m² in the CPAP group, 34.7 kg/m² in the supplemental oxygen group, and 33.7 kg/m² in the education group. Average apnea-hypopnea index scores for the three groups were 25.4, 24.0, and 25.5 events per hour, respectively

That benefit was seen even though those patients’ blood pressure was already well controlled by antihypertensive medications and even though their adherence to CPAP was only "average," said Dr. Gottleib, who is also at Brigham and Women’s Hospital and Harvard Medical School, Boston, and his colleagues.

In contrast, mean arterial blood pressure was not significantly different between patients who received supplemental oxygen and the control group, even though the supplemental oxygen did reduce nocturnal hypoxemia and adherence to oxygen therapy was much better than that for CPAP. A further analysis adjusting for potential confounders such as patient age, sex, race, body mass index, and type of antihypertensive medication had no appreciable effect on the results.

"This study offers no support for the common but largely untested clinical practice of providing supplemental oxygen as salvage therapy in patients with obstructive sleep apnea for whom CPAP is problematic," Dr. Gottlieb and his associates reported (N. Engl. J. Med. 2014;370:2276-85 [doi: 10.1056/NEJMoa1306766]).

In the second study, researchers compared the effects of 24 weeks of CPAP alone, weight loss alone, or CPAP plus weight loss in obese adults who had moderate to severe obstructive sleep apnea and elevated C-reactive protein levels. A total of 181 patients underwent randomization, but only 136 completed the study: 48 in the CPAP group, 42 in the weight-loss group, and 46 in the combined-intervention group, said Dr. Julio A. Chirinos, of the Philadelphia Veterans Affairs Medical Center and the University of Pennsylvania, and his associates.

At the conclusion of the intervention, weight loss was similar between the weight-loss–only group (6.8 kg) and the combined-intervention group (7.0 kg), while there was no change in the CPAP-only group.

The study’s primary endpoint was improvement in C-reactive protein levels. There was no significant difference among the three study groups for this outcome. However, the secondary outcome of significantly decreased systolic blood pressure was achieved with the combined intervention (–14.1 mm Hg), compared with weight loss alone (–6.8 mm Hg) or CPAP alone (–3.0 mm Hg).

The combined therapy also improved insulin resistance and serum triglyceride levels, Dr. Chirinos and his associates said (N. Engl. J. Med. 2014;370:2265-75 [doi: 10.1056/NEJMoa1306187]).

"Our study shows that a weight-loss intervention is effective as a central component of the strategies used to improve the cardiovascular risk-factor profile in patients with obesity and obstructive sleep apnea," they added.

Dr. Gottlieb’s study was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Research Resources. Philips Respironics donated the equipment used in the study. Dr. Gottlieb reported ties to Philips Respironics and ResMed Corporation, and his associates reported ties to numerous industry sources.

Dr. Chirinos’s study also was supported by the NHLBI. ResMed provided CPAP equipment at no cost but had no role in study design, data accrual or analysis, or manuscript preparation. Dr. Chirinos reported no financial conflicts of interest; his associates reported ties to Boehringer Ingelheim, ConAgra Foods, Novo Nordisk, Nutrisystem, Orexigen, Tate and Lyle, United Health Group, and Weight Watchers.

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Encourage weight loss with CPAP use

These studies offer two important considerations to clinicians, noted Dr. Robert C. Basner. First, CPAP may ameliorate hypertension and reduce cardiovascular risk in high-risk obese patients, even when they’re already being treated for hypertension and don’t have the daytime sleepiness that usually characterizes obstructive sleep apnea. Second, weight loss may reduce cardiovascular risks even further when CPAP is prescribed.

But further interpretation of the study findings is limited, Dr. Basner cautioned, because of the relatively low nightly use of CPAP (poor adherence) in the study by Dr. Gottlieb, and because of the wide variability in C-reactive protein values and the unusual statistical handling of those values in the study by Dr. Chirinos.

Dr. Basner is at Columbia University, New York. He was a member of the Data and Safety Monitoring Board of the study performed by Dr. Chirinos. These remarks were taken from his editorial accompanying the two studies (N. Engl. J. Med. 2014;370:2339-41 [doi: 10.1056/NEJMe1404501]).