The role of sleepiness on arterial stiffness improvement after CPAP therapy in males with obstructive sleep apnea: a prospective cohort study

Maria Alexandra Mineiro, Pedro Marques da Silva, Marta Alves, Ana Luísa Papoila, Maria João Marques Gomes, João Cardoso, Maria Alexandra Mineiro, Pedro Marques da Silva, Marta Alves, Ana Luísa Papoila, Maria João Marques Gomes, João Cardoso

Abstract

Background: Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment.

Methods: A selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities was studied. The diagnosis was confirmed by home respiratory poligraphy. Sleepiness was considered with an Epworth Sleepiness Scale (ESS) > 10. An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients.

Results: Thirty-four patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In univariable analysis, cf-PWV was strongly related to systolic BP parameters and age, but also to antihypertensive drugs (p = 0.030), metabolic syndrome (p = 0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA, with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study parameters were not associated with cf-PWV values. On multivariable regression, a significant interaction between time (CPAP) and sleepiness (p = 0.033) was found. There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012). Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure (p = 0.001) and lower LDL-cholesterol levels (p = 0.015) at baseline were associated to higher cf-PWV changes.

Conclusions: Patients with daytime sleepiness had a more severe OSA and presented a greater arterial stiffness improvement after CPAP therapy, independently from age and BP. Besides sleepiness, cf-PWV reduction after CPAP therapy was mainly associated to CV risk factors, and less to sleep study parameters.

Trial registration: Clinicaltrials.gov NCT02273089 23.10.2014 retrospectively registered.

Keywords: Arterial stiffness; Carotid-femoral pulse wave velocity; Daytime sleepiness; Obstructive sleep apnea.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethics Committees of both CHLC (ref. 84/2012) and NOVA Medical School (nr.36/2014/CEFCM), Lisbon. It has been registered as STIFFSLEEP at Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Interaction between ESS group and time regarding cf-PWV measurements. Time: 1-before CPAP; 2- after CPAP. Sleepy group: ESS > 10; non-sleepy group: ESS ≤ 10. ESS- Epworth Sleepiness Scale

References

    1. Epstein LJ, Kristo D, Strollo PJ, Jr, Friedman N, Malhotra A, Patil SP, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. Adult obstructive sleep apnea task force of the American Academy of sleep medicine. J Clin Sleep Med. 2009;5(3):263–276.
    1. Marin JM, Carrizo SJ, Vicente E, Agusti AGN. 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(9464):1046–1053. doi: 10.1016/S0140-6736(05)74229-X.
    1. Ryan S, Taylor CT, McNicholas WT. Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome? Thorax. 2009;85:631–636.
    1. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375:919–931. doi: 10.1056/NEJMoa1606599.
    1. Vlachopoulos C, Xaplanteris P, Aboyans V, et al. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: endorsed by the Association for Research into arterial structure and physiology (ARTERY) society. Atherosclerosis. 2015;241(2):507–532. doi: 10.1016/j.atherosclerosis.2015.05.007.
    1. Vlachantoni IT, Dikaiakou E, Antonopoulos C, Stefanadis C, Daskalopoulou S, Petridou ET. Effects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea in arterial stiffness: a meta-analysis. Sleepmedicine reviews. 2013;17(1):19–28.
    1. Xin L, Chen G, Qi J, Chen X, Zhao J, Lin Q. Effects of continuous positive airway pressure on arterial stiffness in patients with obstructive sleep apnea and hypertension: a meta-analysis. Eur Arch Otorhinolaryngol. 2016;273(12):4081–4088. doi: 10.1007/s00405-016-3914-8.
    1. Kapur VK, Baldwin CM, Resnick HE, Gottlieb DJ, Nieto J. Sleepiness in patients with moderate to severe sleep-disordered breathing. Sleep. 2005;28(4):472–477. doi: 10.1093/sleep/28.4.472.
    1. Duran J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea-hypopnea and related clinical features in a population based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med. 2001;163:685–689. doi: 10.1164/ajrccm.163.3.2005065.
    1. Kohler M, Craig S, Nicoll D, Leeson P, Davies RJO, Stradling JR. Endothelial function and arterial stiffness in minimally symptomatic obstructive sleep apnea. Am J Respir Crit Care Med. 2008;178:984–988. doi: 10.1164/rccm.200805-717OC.
    1. Zhang D, Luo J, Qiao Y. Xiao Yi. Continuous positive airway pressure therapy in non-sleepy patients with obstructive sleep apnea: results of a meta-analysis. Journal of Thoracic Disease. 2016;8(10):2738–2747. doi: 10.21037/jtd.2016.09.40.
    1. Schwab RJ, Badr SM, Epstein LJ, Gay PC, Gozal D, Kohler M. An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults. Am J Respir Crit Care Med. 2013;188(5):613–620. doi: 10.1164/rccm.201307-1282ST.
    1. Johns MWA. New method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–545. doi: 10.1093/sleep/14.6.540.
    1. Mineiro MA, da Silva PM, Alves M, Virella D, Marques Gomes M, Cardoso J. Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol. BMJ Open. 2016;6(7):e011385. doi: 10.1136/bmjopen-2016-011385.
    1. Iber CI, Ancoli-Israel S, Chesson L, et al: for the American Academy of Sleep Medicine. Rules, terminology and technical specifications: The AASM Manual for Scoring of Sleep and Associated Events; 2007.
    1. Suarez M, Osorio J, Torres M, Montserrat JM. Should the diagnosis and management of OSA move into general practice? Breathe. 2016;12(3):243–247. doi: 10.1183/20734735.011216.
    1. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 2009;120:1640–1645. doi: 10.1161/CIRCULATIONAHA.109.192644.
    1. Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2007;176(7):706–712. doi: 10.1164/rccm.200703-500OC.
    1. Kartali N, Daskalopoulou E, Geleris P, Chatzipantazi S, Tziomalos K, Vlachogiannis E, Karagiannis A. The effect of continuous positive airway pressure therapy on blood pressure and arterial stiffness in hypertensive patients with obstructive sleep apnea. Sleep Breath. 2014;18(3):635–640. doi: 10.1007/s11325-013-0926-0.
    1. Chung S, Yoon IY, Lee CH, et al. The effects of nasal continuous positive airway pressure on vascular functions and serum cardiovascular risk factors in obstructive sleep apnea syndrome. Sleep Breath. 2011;15:71. doi: 10.1007/s11325-009-0323-x.
    1. Kohler M, Craig S, Pepperell JC, Nicoll D, Bratton D, Nunn J, et al. CPAP improves endothelial function in patients with minimally symptomatic OSA: results from a subset study of the MOSAIC trial. Chest. 2013;144(3):896–902. doi: 10.1378/chest.13-0179.
    1. Nadeem R, Singh M, Nida M, Kwon S, Sajid H, Witkowski J, et al. Effect of CPAP treatment for obstructive sleep apneahypopnea syndrome on lipid profile: a meta-regression analysis. J Clin Sleep Med. 2014;10(12):1295–1302.
    1. Jullian-Desayes I, Joyeux-Faure M, Tamisier R, Launois S, Anne-Laure B, Levy P, Pepin JL. Impact of obstructive sleep apnea treatment by continuous positive airway pressure on cardiometabolic biomarkers: a systematic review from sham CPAP randomized controlled trials. Sleep Med Rev. 2015;21:251–257. doi: 10.1016/j.smrv.2014.07.004.
    1. Sanner BM, Tepel M, Markmann A, Zidek W. Effects of continuous positive airway pressure therapy on 24-hour blood pressure in patients with obstructive sleep apnea syndrome. Am J Hypertens. 2002;15:3. doi: 10.1016/S0895-7061(01)02292-0.
    1. Wu CF, Liu PY, Wu TJ, Hung Y, Yang SP, Lin GM. Therapeutic modification of arterial stiffness: an update and comprehensive review. WJC. 2015;7(11):742–753. doi: 10.4330/wjc.v7.i11.742.
    1. Oksenberg A, Arons E, Nasser K, Shneor O, Radwan H, Silverberg DS. Severe obstructive sleep apnea: sleepy versus non sleepy patients. Laryngoscope. 2010;120(3):643–648. doi: 10.1002/lary.20758.
    1. Bratton DJ, Stradling JR, Barbé F, Kohler M. Effect of CPAP on blood pressure in patients with minimally symptomatic obstructive sleep apnoea: a meta-analysis using individual patient data from four randomised controlled trials. Thorax. 2014;69(12):1128–1135. doi: 10.1136/thoraxjnl-2013-204993.
    1. Fava C, Dorigoni S, Vedove FD, Danese E, Montagnana M, Guidi GC, et al. Effects of CPAP on blood pressure in patients with OSA/hypopnea: a systematic review and meta-analysis. Chest. 2014;145:762–771. doi: 10.1378/chest.13-1115.
    1. Robinson GV, Langford BA, Smith DM, Stradling JR. Predictors of blood pressure fall with continuous positive airways pressure (CPAP) treatment of obstructive sleep apnoea (OSA) Thorax. 2008;63:855–859. doi: 10.1136/thx.2007.088096.
    1. Colt HG, Haas H, Rich GB. Hypoxemia vs sleep fragmentation as cause of excessive daytime sleepiness in obstructive sleep apnea. Chest. 1991;100(6):1542–1548. doi: 10.1378/chest.100.6.1542.
    1. Mediano O, Barceló A, Pena M, Gozal D, Agusti A, Barbé F. Daytime sleepiness and polysomnographic variables in sleep apnoea patients. Eur Respir J. 2007;30:110–113. doi: 10.1183/09031936.00009506.
    1. Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP. Pathophysiology os sleep apnea. Physiol Rev. 2010;90(1):47–112. doi: 10.1152/physrev.00043.2008.

Source: PubMed

3
Abonnere