Clinical ReviewEffects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea in arterial stiffness: A meta-analysis
Introduction
Obstructive sleep apnea (OSA) is a clinical disorder, which is characterized by recurrent episodes of partial or complete obstruction of the upper airway during sleep, resulting in oxygen desaturation and arousals from sleep. The syndrome is known to affect a substantial number of middle-aged, obese men, whereas, recently, an increasing prevalence among women has been also reported.1 Continuous positive airway pressure (CPAP) is worldwide accepted as the ‘gold standard’ treatment in current management of OSA, as it reduces symptoms and improves quality of life.2
The strong association between OSA and cardiovascular disease (CVD) has attracted considerable interest in recent years. Apnea and hypopnea cause temporary elevations in blood pressure in association with blood oxygen desaturation, arousal and sympathetic activation and may cause elevated blood pressure during the daytime and, ultimately, sustained hypertension.3, 4 Moreover, OSA exposes the cardiovascular (CV) system to intermittent hypoxia, oxidative stress and systemic inflammation which may impair myocardial contractility and cause development and progression of heart failure.5 Moreover, previous evidence suggests that OSA itself is an independent risk factor for cardiovascular morbidity and mortality.6, 7
Arterial stiffness is a composite indicator of arterial health and it is strongly associated with atherosclerosis at various sites in the arterial tree.8, 9 It is caused by structural changes in the vascular wall, including fibrosis, medial smooth muscle cell necrosis, breaks in elastin fibers, calcifications and diffusion of macromolecules into the arterial wall.8, 10, 11 Numerous epidemiological studies have demonstrated that higher arterial stiffness is also associated with increased risk of CVD and cardiovascular events.10, 11, 12
Recent studies have suggested that patients with OSA have increased arterial stiffness, endothelial dysfunction and early signs of atherosclerosis.6 Chung et al.13 found carotid-femoral pulse wave velocity (cfPWV), the ‘gold standard’ measurement of arterial stiffness, to be significantly higher in patients with severe OSA in comparison with patients with mild to moderate OSA and normal controls. Likewise, several studies have also shown a favorable effect of CPAP treatment on arterial stiffness. The role of potential confounding factors, such as obesity, insulin resistance and metabolic syndrome, however, should also be taken into account when exploring this association. The aim of the present meta-analysis is to summarize existing evidence and quantify the potential contribution of CPAP treatment in the improvement of arterial stiffness among patients with OSA.
Section snippets
Data collection
The present meta-analysis was conducted in accordance with the ‘preferred reporting items for systematic reviews and meta-analyses’ (PRISMA) guidelines.14 A combined computerized and manual systematic literature search was performed and the respective publications were identified through Medline, Embase, Scopus, Google Scholar, Ovid and the Cochrane Library. Reference lists were also manually searched for relevant articles.
Types of studies, search terms, eligibility and exclusion criteria
Publications of interest included randomized and non-randomized clinical
Results
As shown in the flow diagram (Fig. 1) 15 articles presenting 17 studies19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 were deemed eligible out of 101 potentially relevant articles, including a total of 615 patients. Of these studies, none was performed on mutually overlapping populations. A careful review of the included studies was performed in order to ensure that no individual participating in one eligible study participated in any other study included in the meta-analysis, thus
Discussion
The findings of the present meta-analyses, comprising of 615 OSA patients, suggested that CPAP may be an effective intervention for the reduction of arterial stiffness in patients with OSA. In particular, a significant improvement of arterial stiffness was found when all outcome measures of arterial stiffness were pooled together. Moreover, in the subsequent meta-analyses among studies using the same arterial stiffness measure we found that CPAP treatment was associated with a 4.86% improvement
Conflict of interest
None declared.
Acknowledgments
This study was supported in part by the Medical School of the National and Kapodistrian University of Athens.
References∗ (62)
The relationship between systemic hypertension and obstructive sleep apnea: facts and theory
Am J Med
(1995 Feb)- et al.
Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications
J Am Coll Cardiol
(2011 Jan 11) - et al.
Obstructive sleep apnea and atherosclerosis
Prog Cardiovasc Dis
(2009 Mar-Apr) - et al.
Obstructive sleep apnea and cardiovascular disease: a perspective and future directions
Prog Cardiovasc Dis
(2009 Mar-Apr) - et al.
Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis
J Am Coll Cardiol
(2010 Mar 30) - et al.
Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares
Lancet
(1981) - et al.
Effect of CPAP on brachial-ankle pulse wave velocity in patients with OSAHS: an open-labelled study
Respir Med
(2006 Dec) - et al.
Effects of continuous positive airway pressure treatment and withdrawal in patients with obstructive sleep apnea on arterial stiffness and central BP
Chest
(2008 Jul) - et al.
Continuous positive nasal airway pressure decreases levels of serum amyloid A and improves autonomic function in obstructive sleep apnea syndrome
Int J Cardiol
(2009 Jul 10) - et al.
Effects of CPAP therapy on the sympathovagal balance and arterial stiffness in obstructive sleep apnea
Respir Med
(2010 Jun)
Continuous positive airway pressure therapy improves arterial elasticity in patients with obstructive sleep apnea
Respir Med
Change in cardio-ankle vascular index by long-term continuous positive airway pressure therapy for obstructive sleep apnea
J Cardiol
Effect of different antihypertensive drug classes on central aortic pressure
Am J Hypertens
Obstructive sleep apnea and inflammation
Prog Cardiovasc Dis
Oxidative stress–a unifying paradigm in obstructive sleep apnea and comorbidities
Prog Cardiovasc Dis
Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea
J Cardiovasc Magn Reson
Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea
Circulation
Prospective study of the association between sleep-disordered breathing and hypertension
N Engl J Med
Arterial stiffness, fatness, and physical fitness: ready for intervention in childhood and across the life course?
Hypertension
Correlation of ultrasound-measured common carotid artery stiffness with pathological findings
Arterioscler Thromb
Arterial stiffness and cardiovascular events: the Framingham heart study
Circulation
Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients
Hypertension
The association of nocturnal hypoxemia with arterial stiffness and endothelial dysfunction in male patients with obstructive sleep apnea syndrome
Respiration
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration
BMJ
A new system for grading recommendations in evidence based guidelines
BMJ
A new method for measuring daytime sleepiness: the Epworth sleepiness scale
Sleep
Cochrane handbook for systematic reviews of interventions v5.0.2
Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea
Am J Respir Crit Care Med
CPAP and measures of cardiovascular risk in males with OSAS
Eur Respir J
Effect of continuous positive airway pressure therapy on aortic stiffness in patients with obstructive sleep apnea syndrome
Echocardiography
Cited by (59)
A State-of-the-Art Review on Sleep Apnea Syndrome and Heart Failure
2023, American Journal of CardiologySleep-disordered breathing in high-risk pregnancies is associated with elevated arterial stiffness and increased risk for preeclampsia
2022, American Journal of Obstetrics and GynecologyDiurnal changes in central blood pressure and pulse pressure amplification in patients with obstructive sleep apnoea
2019, International Journal of Cardiology: HypertensionCitation Excerpt :The combined effects would be neutral. The increase in wave reflection (AP,AIx and CAIx75) during wakefulness after CPAP is contrary to the findings from other studies using static office-based measurements which have consistently shown a reduction [51, 52]. Similarly, an attenuated PPA dip with CPAP is difficult to explain seeing as the expected effects of treatment overnight such as a reduction in sympathetic activity, and reduction in left ventricular afterload, should all theoretically cause a further reduction in sleep PPA.
Which place of pharmacological approaches beyond continuous positive airway pressure to treat vascular disease related to obstructive sleep apnea?
2018, Pharmacology and TherapeuticsCitation 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).
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The most important reference is denoted by an asterisk.