Elsevier

Sleep Medicine

Volume 14, Issue 12, December 2013, Pages 1260-1265
Sleep Medicine

Original Article
The effect of continuous positive airway pressure therapy on arterial stiffness and endothelial function in obstructive sleep apnea: a randomized controlled trial in patients without cardiovascular disease

https://doi.org/10.1016/j.sleep.2013.08.786Get rights and content

Abstract

Background

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality which may be mediated by increased arterial stiffness and endothelial dysfunction. Continuous positive airway pressure (CPAP) therapy improves excessive daytime somnolence (EDS), but its effect on vascular function in patients without preexisting cardiovascular disease (CVD) is unclear.

Methods

Fifty-three patients with OSA defined as an apnea–hypopnea index (AHI) of ⩾15 and without CVD were recruited into a double-blind, randomized, placebo-controlled, crossover trial of 12 weeks of CPAP therapy, of whom 43 participants completed the study protocol. Arterial stiffness was assessed by measuring the augmentation index (AIx) and pulse wave velocity (PWV) by applanation tonometry and cardiovascular magnetic resonance imaging to determine aortic distensibility. Endothelial function was assessed by measuring vascular reactivity after administration of salbutamol and glyceryl trinitrate.

Results

CPAP therapy lowered systolic blood pressure (SBP) (126 mmHg [standard deviation {SD}, 12] vs 129 mmHg [SD, 14]; P = .03), with a trend towards reduced AIx (15.5 [SD, 11.9] vs 16.6 [SD, 11.7]%; P = .08) but did not modify endothelial function. When subjects with (n = 24) and without (n = 19) EDS were separately examined, no effect of CPAP therapy on vascular function was seen.

Conclusions

In patients without overt CVD, CPAP therapy had a nonsignificant effect on AIx and did not modify endothelial function.

Introduction

Obstructive sleep apnea (OSA) is common and is caused by repetitive obstruction of the upper airway during sleep. When OSA leads to excessive daytime somnolence (EDS) it is termed obstructive sleep apnea–hypopnea syndrome (OSAHS), affecting 2–4% of the middle-aged population with an even greater proportion having evidence of OSA without EDS [1].

OSA is associated with increased cardiovascular morbidity and mortality [2], [3] and is an independent risk factor for hypertension [4]. Many mechanisms linking OSA and cardiovascular disease (CVD) have been proposed, with individual obstructive events associated with transient increases in blood pressure (BP) [5], arterial stiffness [6], and sympathetic activity [7]; all of which, along with systemic inflammation [8] and intrathoracic pressure swings, may contribute to endothelial dysfunction. We previously showed [9] that subjects with OSAHS in the absence of known CVD had evidence of increased arterial stiffness and impaired endothelial function when compared to well-matched control subjects.

Observational studies suggest that cardiovascular morbidity and mortality is lower in patients treated with continuous positive airway pressure (CPAP) therapy [2], [10], [11]. Randomized controlled trials (RCTs) have shown that CPAP therapy lowers BP [12], [13], and it also has been shown to improve endothelial function in small studies [14], [15]; however, many of these studies did not exclude patients with CVD [12], [13], [15]. To our knowledge, the effects of CPAP therapy on arterial stiffness had not yet been investigated prior to beginning our trial.

The aim of our double-blind, randomized, placebo-controlled, crossover trial was to examine the effects of CPAP therapy on arterial stiffness and endothelial function in subjects with OSA in the absence of overt CVD or diabetes mellitus (DM).

Section snippets

Subjects

Fifty-three subjects with OSA (apnea–hypopnea index [AHI] of ⩾15 on polysomnography), with no history of CVD or DM, were recruited through the Department of Sleep Medicine, Royal Infirmary of Edinburgh (Fig. 1). Exclusion criteria were previous CPAP therapy, respiratory failure, medications affecting BP, sleepiness when driving, professional driving, contraindications to magnetic resonance imaging, and intercurrent illness. EDS was defined as a score of ⩾11 on the Epworth Sleepiness Scale

Baseline characteristics and vascular measurements

Fifty-three subjects with OSA underwent baseline vascular assessments, of whom 10 did not complete the RCT (Fig. 1); baseline data for these subjects did not significantly differ from the 43 patients who completed the study. Baseline characteristics for those completing the study are shown in Table 1. The median AHI was 31, suggesting moderate disease severity; however, the mean minimum oxygen saturations were relatively high and the mean percentage of sleep time spent with oxygen saturations

Discussion

In a rigorous, double-blind, randomized, placebo-controlled, crossover trial, CPAP therapy lowered SBP with a trend towards a reduction in AIx after 12 weeks. However, CPAP therapy had no effect on PWV, AoD, or endothelial function in this group of subjects without CVD after 12 weeks.

OSA is associated with increased cardiovascular morbidity and mortality [2], [3], and numerous mechanisms are proposed. Using the same measures, we previously showed [9] that subjects with OSA and EDS had increased

Conclusions

In this group of subjects with relatively mild OSA in the absence of CVD or DM and in the context of a rigorous, double-blind, randomized, placebo-controlled crossover trial, we found that CPAP therapy lowered BP but had a nonsignificant effect on arterial stiffness, as measured by AIx, and did not modify endothelial function. Although it is clear that CPAP therapy is an effective treatment for EDS, more evidence is required, especially in patients with less severe OSA who do not have evidence

Funding sources

This study was funded by a British Heart Foundation project grant (PG/06/092/21267). We thank Dr. Tom Mackay and all of the staff within the Department of Sleep Medicine, the Department of Radiology and the Clinical Research Facility at the Royal Infirmary of Edinburgh.

Conflict of interest

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2013.08.786.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

References (38)

  • J. Hedner et al.

    Is high and fluctuating muscle nerve sympathetic activity in the sleep apnoea syndrome of pathogenetic importance for the development of hypertension?

    J Hypertens Suppl

    (1988)
  • S. Ryan et al.

    Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome?

    Postgrad Med J

    (2009)
  • F. Campos-Rodriguez et al.

    Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study

    Ann Intern Med

    (2012)
  • J.M. Marin et al.

    Association between treated and untreated obstructive sleep apnea and risk of hypertension

    JAMA

    (2012)
  • J.F. Faccenda 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)
  • M.S. Ip et al.

    Endothelial function in obstructive sleep apnea and response to treatment

    Am J Respir Crit Care Med

    (2004)
  • M.D. Cross et al.

    Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial

    Thorax

    (2008)
  • A. Rechtschaffen et al.

    A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects

    (1968)
  • C. Iber et al.

    The American academy of sleep medicine manual for the scoring of sleep and associated events: rules, terminology and technical specifications

    (2007)
  • Cited by (41)

    • The connection between obstructive sleep apnea and peripheral artery disease

      2020, Journal of Vascular Nursing
      Citation Excerpt :

      In addition, encouraging patient compliance in wearing prescribed continuous positive airway pressure (CPAP) devices not only improves the quality of sleep (and therefore, the quality of life) but may contribute to a reduction in arterial intima-media wall thickness, an early sign of atherosclerosis.29 A reduction in blood pressure may also occur with CPAP compliance; however, study results here are conflicted.30,31 Including education and closer monitoring of medications that may adversely affect the oxygenation/ventilation status of an OSA patient include opioids, benzodiazepines, skeletal muscle relaxants, and drugs that are associated with weight gain such as antihistamines, antidepressants, antidiabetics, and antipsychotics will assist in reducing these complications.32

    • Which place of pharmacological approaches beyond continuous positive airway pressure to treat vascular disease related to obstructive sleep apnea?

      2018, Pharmacology and Therapeutics
      Citation Excerpt :

      A RCT conducted in moderate to severe OSA patients [median and interquartile range of AHI of 31(20–41) events/h], without overt CVD, demonstrated that 12 weeks of CPAP therapy had no effect on endothelial function and a non-significant trend towards a lowering of arterial stiffness (Jones et al., 2013). These discrepancies within the literature (Phillips, Butlin, et al., 2013; Vlachantoni et al., 2013) may be explained by less severe vascular dysfunction, in terms of endothelial function and arterial stiffness, in the particular subgroup of OSA patients (Jones et al., 2013) who are free of CVD and exhibit fewer nocturnal desaturations (Ryan, 2013). The influence of baseline CVD on the response to CPAP is also supported by the results of the SAVE study in which CPAP provided no benefit in terms of the reduction of cardiovascular events in patients with moderate to severe OSA in secondary cardiovascular prevention (McEvoy et al., 2016; Mokhlesi & Ayas, 2016).

    • Obstructive sleep apnea and arrhythmia: A systemic review

      2017, International Journal of Cardiology
    View all citing articles on Scopus
    View full text