对于高血压患者应CPAP与减重双管齐下

旧金山——一项纳入181例成人患者的研究显示，在降低肥胖的睡眠呼吸暂停患者的收缩压方面，为期24周的减轻体重联合持续正压通气(CPAP)计划的效果明显优于单一干预手段。

意向治疗分析显示，所有三组患者的收缩压均比极限水平显著下降，其中联合治疗组降低了大约8 mmHg，两个单一治疗组各降低了4 mmHg，三组的下降幅度无统计学差异。但在136例按照所在组的治疗方案完成试验的患者中，联合治疗组的62例患者的收缩压平均下降14 mmHg，而单纯减重组的61例患者和单纯CPAP组的58例患者分别下降7 mmHg和3 mmHg，联合治疗组有明显优势。


Julio A. Chirinos博士
 
宾夕法尼亚大学的Julio A. Chirinos博士在美国心脏病学会(ACC)2013年会上指出，收缩压下降14 mmHg“意义重大”，有可能给肥胖的睡眠呼吸暂停患者带来显著的临床益处。

既往观察性研究显示，肥胖、阻塞性睡眠呼吸暂停与高血压之间有强烈关联，但未能确定联合治疗肥胖和睡眠呼吸暂停是否有额外的血压获益。为此，Chirinos博士及其同事对“阻塞性睡眠呼吸暂停的心血管后果”试验的数据进行了辅助分析。该试验主要关注治疗对C反应蛋白(CRP)水平的影响，将至少轻度肥胖、中至重度阻塞性睡眠呼吸暂停且CRP＞1 mg/L的成年患者随机分为3个干预组。三组患者的基线特征相似。大约41%的患者基线时患有高血压。

对于能够依从治疗的患者进行完成治疗分析，研究者发现，与基线水平相比，联合治疗组和单纯减重组患者的收缩压下降具有统计学意义，而单纯CPAP组的下降不显著。

与此相似，联合治疗组和单纯减重组患者的体重和体重指数(BMI)相比基线水平显著下降，而单纯CPAP组的下降不显著。在意向治疗分析中，联合治疗组和单纯减重组的体重下降幅度约为7 kg，而在完成治疗分析中，这两组的体重下降幅度为10~11 kg。在意向治疗分析中，BMI平均降低2~3 kg/m²，在完成治疗分析中，BMI大约降低了4 kg/m²。研究者未提供减重方法的细节。

不论采用哪种分析，三组患者的平均动脉压均比基线水平显著降低。但在完成治疗分析中，联合治疗组的下降幅度比单一治疗组更显著(下降10 mmHg以上 vs. 下降大约4 mmHg)。

在意向治疗分析中，与基线水平相比，仅有联合治疗组患者的肱动脉脉压显著下降(降低大约3 mmHg)。在完成治疗分析中，联合治疗组(降低6 mmHg)和单纯减重组(降低4 mmHg)的肱动脉脉压显著低于基线水平，而单纯CPAP组患者的肱动脉脉压反而有所升高。

三组的颈-桡脉压放大指标相对于基线水平均无明显改变，提示该研究结果不会因遗漏中心脉压的某些改变而发生变化。

总体上，约有50%的阻塞性睡眠呼吸暂停患者合并高血压，约有30%的高血压患者合并阻塞性睡眠呼吸暂停。

上述研究结果的局限性在于：招募和排除患者的标准非常严格(排除了血压＞160/95 mmHg、以中枢性为主的睡眠呼吸暂停、接受补氧、从事高危职业或有危险驾驶记录的患者，还排除了有系统性炎症、持续心律不齐、不稳定心肺疾病、严重不宁退综合征或慢性疼痛导致夜间频繁觉醒、妊娠、重性抑郁的患者，患有其他严重躯体或精神疾病而可能影响研究安全性的患者，以及入组前8周内曾使用CPAP的患者)，未进行动脉血压监测，采用非侵入性手段(颈压测量法)估算中心脉压，以及为期仅6个月。

美国心脏协会(AHA)资助了Chirinos博士的分析。Chirinos博士报告称无相关利益冲突。部分合著者报告称与多家制药公司存在利益关系。

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By: SHERRY BOSCHERT, Cardiology News Digital Network

SAN FRANCISCO– A 24-week program combining weight-loss efforts with continuous positive airway pressure produced significantly greater reductions in systolic blood pressure in obese patients with obstructive sleep apnea, compared with either intervention alone, a study of 181 adults found.

In an intent-to-treat analysis, all three groups reduced systolic pressures to a statistically similar extent, compared with baseline – decreases of approximately 8 mm Hg in the combination group and 4 mm Hg with either monotherapy. Among 136 patients who adhered to therapy by completing the trial, however, systolic blood pressure decreased by a mean of 14 mm Hg in the 62 patients randomized to the combination of weight-loss efforts and continuous positive airway pressure (CPAP), a significantly greater decrease than the reductions of approximately 7 mm Hg in 61 patients randomized to weight-loss efforts alone and 3 mm Hg in 58 patients who got CPAP alone.

A 14 mm Hg–drop in systolic blood pressure is an "important reduction" with potentially significant clinical benefits in obese patients with obstructive sleep apnea, Dr. Julio A. Chirinos said at the annual meeting of the American College of Cardiology.

Previous observational studies have shown strong associations in obesity, obstructive sleep apnea, and hypertension but have not been able to assess whether there is any incremental blood pressure benefit to combining treatments for obesity and sleep apnea.

Dr. Chirinos and his associates conducted an ancillary analysis of data from the Cardiovascular Consequences of Obstructive Sleep Apnea trial, which focused primarily on the treatments’ effects on C-reactive protein levels. The study randomized adults with at least moderate obesity and moderate to severe obstructive sleep apnea and C-reactive protein levels greater than 1 mg/L to the three intervention groups. Baseline characteristics were similar among groups. Approximately 41% of patients were hypertensive at baseline.

In the per-protocol analysis of patients who adhered to therapy, the decreases in systolic blood pressure, compared with baseline, were statistically significant in the combination and weight-loss groups but not the CPAP group, reported Dr. Chirinos of the University of Pennsylvania, Philadelphia.

Body weight and body mass index decreased significantly in the weight-loss and combination groups compared with baseline but did not change significantly in the CPAP group. Patients in the weight-loss and combination groups dropped approximately 7 kg in the intent-to-treat analysis and 10-11 kg in the per-protocol analysis. Body mass index decreased by a mean of two to three points in the intent-to-treat analysis and by approximately four points among those who adhered to therapy. No details were provided about the specifics of the weight-loss efforts.

Mean arterial pressure decreased significantly in all three groups, compared with baseline, in both intent-to-treat and per-protocol analyses, but fell significantly more in the combination group, compared with monotherapy, in the per-protocol analysis. Among patients adherent to treatment, mean arterial pressure decreased by more than 10 mm Hg in the combination group, compared with approximately 4 mm Hg–declines with either monotherapy.

Only combination therapy significantly reduced brachial pulse pressure, compared with baseline (by approximately 3 mm Hg), in the intent-to-treat analysis. In the per-protocol analysis, brachial pulse pressure dropped significantly, compared with baseline, in the combination group (a 6 mm Hg decrease) and the weight-loss group (a 4 mm Hg–decrease) but not in the CPAP group.

Brachial pulse pressure decreased significantly with combination therapy in the intent-to-treat analysis but not with either treatment alone. Mean brachial pulse pressure in the per-protocol analysis decreased significantly with combination therapy (a 6 mm Hg–reduction) or weight-loss therapy (a 4 mm Hg–decrease) but increased in the CPAP group.

Carotid-radial pulse pressure amplification measurements did not change significantly from baseline in any group, suggesting that the study’s results were not brought about by missing some changes in central pressure that were not being picked up by brachial measurements, Dr. Chirinos said.

In general, approximately 50% of people with obstructive sleep apnea have hypertension, and around 30% of hypertensive patients have obstructive sleep apnea, he said.

The findings are limited by the study’s strict criteria for patient inclusion or exclusion, its lack of arterial blood pressure monitoring, the use of noninvasive estimates of central pressure measurements, and its duration of only 6 months. The study used carotid tonometry to measure central pulse pressure.

The study excluded patients with blood pressures greater than 160/95 mm Hg, those with predominantly central sleep apnea, patients using supplemental oxygen, and anyone in a high-risk occupation or with a record of dangerous driving. Also excluded were patients with confounders of systemic inflammation, sustained arrhythmia, unstable cardiopulmonary disease, severe restless leg syndrome or chronic pain causing frequent night awakenings, pregnancy, severe depression or other serious medical or psychological conditions that might compromise their safety in the study, and prior CPAP within 8 weeks of the study.

The American Heart Association funded Dr. Chirinos’s analysis. Dr. Chirinos reported having no financial disclosures. Some of his associates reported financial relationships with multiple pharmaceutical companies.