Editor's Note: Commentary based on Pépin JL, Tamisier R, Baguet JP, Lévy P. Arterial health is related to obstructive sleep apnea severity and improves with CPAP treatment. Sleep Med Rev 2013;17:3-5.

Background

Obstructive sleep apnea (OSA) is associated with increased arterial stiffness, a cumulative indicator of arterial health. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA.

Methods

A meta-analysis of the available literature investigating the effect of CPAP on arterial stiffness in patients with OSA was conducted. Fifteen articles (n = 615 patients) assessing indices of arterial stiffness were identified. Five different meta-analyses were performed assessing: a) all indices of arterial stiffness, b) augmentation index (AIx), c) all pulse wave velocities (PWV), d) brachial-ankle PWV and e) carotid-femoral PWV. Pooled standardized mean differences (SMDs) and weighted mean differences (WMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity.

Results

A significant improvement of all indices of arterial stiffness was observed after CPAP treatment (SMD = -0.74; 95%CI: -1.08 to -0.41). AIx and PWVs were also significantly improved (WMD = -4.86; 95%CI: -7.31 to -2.41 and WMD = -0.87; 95%CI: -0.98 to -0.77, respectively), as well as brachial-ankle PWV and carotid-femoral PWV (WMD = -0.86; 95%CI: -0.97 to -0.75 and WMD = -1.21; 95%CI:-1.92 to -0.50, respectively). Neither the proportion of compliant patients nor the duration of CPAP use altered the effect of arterial stiffness reduction after CPAP treatment.

Conclusion

In conclusion, this study showed significant improvements in all indices of arterial stiffness after CPAP treatment in patients with OSA. As clinical use of arterial stiffness is growing in popularity, the efficacy of this useful tool in assessing cardiovascular risk reduction among patients with OSA treated with CPAP needs to be further explored.

Commentary/Perspective

Obstructive sleep apnea (OSA) has become an important risk factor for cardiovascular disease (CVD).^1-2 Although OSA was clinically recognized as a disease approximately three decades ago, awareness of the condition outside the specialized field of sleep medicine has been slow to develop, and most of those affected, remain undiagnosed.³ Recent evidence indicates that OSA is strongly associated with many CVD deemed idiopathic or essential,¹ raising the question of whether there may be a causal relationship. Such conditions include hypertension, dyslipidemia, coronary artery disease, cardiac arrhythmias, congestive heart failure, pulmonary hypertension, and stroke. Small and short-term controlled interventional trials, particularly assessing blood pressure,⁴ and large cohort studies⁵ have suggested that treatment of OSA can impact CVD outcomes, but large randomized controlled trials to better inform clinical practice are lacking.

Until such data are available, studies like that from Vlachantoni et al. continue to advance our understanding of the relationship between OSA, its treatment and vascular disease.⁶ Their meta-analysis revealing significant improvement in all indices of arterial stiffness after continuous positive airway pressure (CPAP) treatment, underscores the importance of early vascular dysfunction assessment in OSA. It is well known that endothelial dysfunction and arterial stiffness mark the onset of atherosclerosis and are associated with adverse CVD events.⁷ Although various measures of arterial stiffness have been proposed as CVD risk markers, they are not yet accepted into clinical practice. For these indices to become clinically important surrogate markers, they should: 1) provide independent information above currently used risk markers; 2) be reliably and reproducibly measured; 3) account for a significant proportion of CVD risk; 4) provide good predictive value; 5) be reasonably associated with the underlying pathophysiology; and 6) be present before the clinical appearance of the CVD. While multiple studies have validated arterial stiffness as a CVD risk marker in wide range of patient populations,⁷ large community-based outcome studies are still needed to clarify the position of arterial stiffness assessment in clinical practice.

Yet unanswered: Will there be a point of advanced vascular dysfunction prohibiting return to normal vascular function? Furthermore, since the majority of patients in Vlachantoni et al. study were middle-aged men with at least moderate OSA, will their findings hold true for women, or particular racial/ethnic groups, or those with severe OSA and extreme arterial stiffness severity scores?

There is need for longitudinal studies including both genders and minority population, in order to evaluate whether a significant reduction in future cardiovascular events may be predicted by lowering arterial stiffness with early CPAP treatment.

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References

1. Chami HA, Resnick HE, Quan SF et al. Association of incident cardiovascular disease with progression of sleep-disordered breathing. Circulation. 2011;123:1280‒6.
2. Olafiranye O, Akinboboye O, Mitchell JE, Ogedegbe O, Jean-Louis G. Obstructive Sleep and Cardiovascular Disease in Blacks: A call to Action from Association of Black Cardiologist. Am Heart J 2013;165:468-76.
3. Rosen RC, Zozula R, Jahn EG et al. Low rates of recognition of sleep disorders in primary care: comparison of a community-based versus clinical academic setting. Sleep Med 2001;2:47–55.
4. Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, Davies RJ. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet 2002:359:204-10.
5. Marin JM, Carrizo SJ, Vicente E et al. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005:365:1046-53.
6. Vlachantoni IT, Dikaiakou E, Antonopoulos CN, Stefanadis C, Daskalopoulou SS, Petridou ET. Effects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea in arterial stiffness: a meta-analysis. Sleep Med Rev. 2013 Feb;17(1):19-28.
7. Mitchell GF, Hwang SJ, Vasan RS, et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation 2010; 121: 505–511.

Keywords: Arrhythmias, Cardiac, Blood Pressure, Cardiovascular Diseases, Coronary Artery Disease, Coronary Disease, Dyslipidemias, Heart Failure, Hypertension, Hypertension, Pulmonary, Risk Factors, Sleep Apnea, Obstructive, Stroke

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