Elsevier

The Lancet

Volume 359, Issue 9302, 19 January 2002, Pages 204-210
The Lancet

Articles
Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial

https://doi.org/10.1016/S0140-6736(02)07445-7Get rights and content

Summary

Background

Obstructive sleep apnoea is associated with raised blood pressure. If blood pressure can be reduced by nasal continuous positive airway pressure (nCPAP), such treatment could reduce risk of cardiovascular disease in patients with obstructive sleep apnoea. Our aim was to see whether nCPAP for sleep apnoea reduces blood pressure compared with the most robust control intervention subtherapeutic nCPAP.

Methods

We did a randomised parallel trial to compare change in blood pressure in 118 men with obstructive sleep apnoea (Epworth score >9, and a >4% oxygen desaturation index of >10 per h) who were assigned to either therapeutic (n=59) or subtherapeutic (59) nCPAP (about 1 cm H2O pressure) for 1 month. The primary outcome was the change in 24-h mean blood pressure. Secondary outcomes were changes in systolic, diastolic, sleep, and wake blood pressure, and relations between blood pressure changes, baseline blood pressure, and severity of sleep apnoea.

Findings

Therapeutic nCPAP reduced mean arterial ambulatory blood pressure by 2·5 mm Hg (SE 0·8), whereas subtherapeutic nCPAP increased blood pressure by 0·8 mm Hg (0·7) (difference −3·3 [95% CI −5·3 to −1·3]; p=0·0013, unpaired t test). This benefit was seen in both systolic and diastolic blood pressure, and during both sleep and wake. The benefit was larger in patients with more severe sleep apnoea than those who had less severe apnoea, but was independent of the baseline blood pressure. The benefit was especially large in patients taking drug treatment for blood pressure.

Interpretation

In patients with most severe sleep apnoea, nCPAP reduces blood pressure, providing significant vascular risk benefits, and substantially improving excessive daytime sleepiness and quality of life.

Introduction

In more-developed countries, 2–4% of adult men, and about 1% of adult women have detectable obstructive sleep apnoea,1, 2 and up to 1·5% of men in the UK have moderate or severe disease.3 Sleep apnoea is caused by the collapse of the pharynx during sleep, which leads to airway occlusion and transient asphyxia. Asphyxia is reversed when the patient wakes and pharyngeal muscle tone returns to wake levels. These events are repetitive, with severely affected patients having hundreds of obstructive episodes and arousals every night. Both nocturnal and daytime blood pressure are raised in patients with obstructive sleep apnoea. This effect is seen in community-based epidemiological studies4, 5 and hospital clinic populations,6 and is independent of obesity and other risk factors for raised blood pressure that are prevalent in this population.4, 5, 6

The standard treatment for sleep apnoea is nasal continuous positive airway pressure (nCPAP), and if this treatment reduces blood pressure it should also reduce vascular risk, which is high in patients with this disorder.7 Results of observational cohort studies8, 9 and of a small crossover trial controlled by an oral placebo10 suggest that blood pressure falls in patients with sleep apnoea who are given nCPAP. However, existing data11, 12 have been strongly criticised for not being adequately controlled, and vigorous debate about the effect of sleep apnoea treatment on vascular risk has resulted. For example, Phillipson13 has described sleep apnoea as a vascular risk factor that is “as important as diabetes”, whereas in another editorial,14 the argument is that this disorder “may not be a disease at all”. Wright and colleagues11 have emphasised the need for methodologically robust trials to settle this debate, since the large symptomatic placebo effects seen with subtherapeutic nCPAP15 probably change physical activity and diet, and hence blood pressure. We have addressed this uncertainty by comparing changes in ambulatory blood pressure when nCPAP treatment is used for obstructive sleep apnoea with those of the most robust control therapy available, subtherapeutic nCPAP.

Section snippets

Design and setting

We did a parallel, randomised, double-blind trial of patients in the Sleep and Respiratory Trials Units, Oxford Centre for Respiratory Medicine, Oxford, UK. The unit takes patients who have been referred with possible obstructive sleep apnoea from the surrounding region. About a third of patients are from the Oxford area. Referrals are made by general practitioners (36%); ear, nose, and throat surgeons (41%); or other hospital consultants (23%).

Patients

Patients were eligible for the trial if they were

Results

Figure 1 shows the trial profile. Of the 339 eligible patients, 67 had been included in our previous study of sleepiness in obstructive sleep apnoea.15 Blood pressure measurement was added to this previous protocol after it had received ethical approval and after it was established to be manageable within the protocol. Patients who declined to take part did so mainly because of the extra time needed to participate, or the distance to travel. The severity of sleep apnoea was similar between

Discussion

Our results showed a significant fall from baseline of 3·3 mm Hg in mean ambulatory blood pressure in patients with moderate or severe obstructive sleep apnoea when given therapeutic nCPAP compared with patients on subtherapeutic nCPAP. Similar reductions were seen in systolic and diastolic blood pressure during both sleep and wake times. This result directly addresses a deficit in the evidence of the blood pressure response to nCPAP therapy in patients with sleep apnoea; specifically, the

References (42)

  • StradlingJR et al.

    Prevalence of sleepiness and its relation to autonomic evidence of arousals and increased inspiratory effort in a community based population of men and women

    J Sleep Res

    (2000)
  • PeppardPE et al.

    Prospective study of the association between sleep-disordered breathing and hypertension

    N Engl J Med

    (2000)
  • NietoFJ et al.

    Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study

    JAMA

    (2000)
  • DaviesCWH et al.

    Case-control study of 24 hour ambulatory blood pressure in patients with obstructive sleep apnoea and normal matched control subjects

    Thorax

    (2000)
  • ShaharE et al.

    Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study

    Am J Respir Crit Care Med

    (2001)
  • WilcoxI et al.

    Effect of nasal continuous positive airway pressure during sleep on 24-hour blood pressure in obstructive sleep apnea

    Sleep

    (1993)
  • AkashibaT et al.

    Daytime hypertension and the effects of short-term nasal continuous positive airway pressure treatment in obstructive sleep apnea syndrome

    Intern Med

    (1995)
  • FaccendaJF et al.

    Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome

    Am J Respir Crit Care Med

    (2001)
  • WrightJ et al.

    Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence

    BMJ

    (1997)
  • PhillipsonEA

    Sleep apnea—a major public health problem

    N Engl J Med

    (1993)
  • Deep and shallow truths

    BMJ

    (1997)
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