Advertisement

Sleep and Breathing

, Volume 23, Issue 1, pp 77–86 | Cite as

Effects of continuous positive airway pressure on cardiovascular biomarkers in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials

  • Yu Ning
  • Tian-Song Zhang
  • Wan-Wan Wen
  • Kun Li
  • Yun-Xiao Yang
  • Yan-Wen Qin
  • Hui-Na Zhang
  • Yun-Hui Du
  • Lin-Yi Li
  • Song Yang
  • Yun-Yun Yang
  • Miao-Miao Zhu
  • Xiao-Lu Jiao
  • Yan Zhang
  • Ming ZhangEmail author
  • Yong-Xiang WeiEmail author
Sleep Breathing Physiology and Disorders • Original Article

Abstract

Purpose

Obstructive sleep apnea (OSA) is associated with increased levels of systemic inflammatory markers, increased arterial stiffness, and endothelial dysfunction, which may lead to increased cardiovascular risk. We aimed to quantify the effects of continuous positive airway pressure (CPAP) on cardiovascular biomarkers and to establish predictors of response to CPAP.

Methods

We searched PubMed and the Cochrane Library from inception to May 31, 2017. Randomized controlled trials (RCTs) assessing the efficacy of CPAP on high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor- alpha (TNF-α), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) in patients with OSA were selected by consensus.

Results

We included 15 RCTs comprising 1090 patients in the meta-analysis. The pooled standard mean difference (SMD) of effect of CPAP on hs-CRP was − 0.64 (95% confidence interval (CI) − 1.19 to − 0.09; P = 0.02). CPAP was associated with a reduction in AIx of 1.53% (95% CI, 0.80 to 2.26%; P < 0.001) and a significant increase in FMD of 3.96% (95% CI 1.34 to 6.59%; P = 0.003). Subgroup analyses found CPAP was likely to be more effective in improving FMD levels in severe OSA patients or patients with effective CPAP use ≥ 4 h/night.

Conclusions

Among patients with OSA, CPAP improves inflammatory marker hs-CRP, arterial stiffness marker AIx, and endothelial function marker FMD. These biomarkers may provide information related to response to treatment. Future studies will need to clarify the efficacy of these biomarkers in assessing cardiovascular risk reduction among OSA treated with CPAP.

Keywords

Continuous positive airway pressure Cardiovascular biomarker Obstructive sleep apnea Meta-analysis 

Notes

Author contributions

Drs. Y.N., M.Z., and Y.X.W. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Y.N., M.Z., T.S.Z., and Y.X.W. conceived and designed the study. Y.N. and T.S.Z. reviewed the scientific literature, did the statistical analysis, prepared all tables and figures, and wrote the first draft of the report. Y.N., T.S.Z., and W.W.W. contributed to acquisition of data and quality assessment. M.Z. and Y.X.W. reviewed and revised the article. All authors made a critical revision of the manuscript for key intellectual content.

Funding

This work was supported by International Science & Technology Cooperation Program of China (2015DFA30160); Beijing Municipal Science & Technology Commission (Z141100006014057); Beijing Key Laboratory of upper airway dysfunction related cardiovascular diseases (BZ0377); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201605); Beijing Medical Project 2016-4; and Beijing Municipal Training Foundation for Highly-qualified and Technological Talents of Health System (2014-3-038).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval was not necessary for this meta-analysis, as only identified pooled data from previously approved individual studies was used.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11325_2018_1662_MOESM1_ESM.doc (126 kb)
ESM 1 (DOC 125 kb)
11325_2018_1662_MOESM2_ESM.docx (287 kb)
ESM 2 (DOCX 286 kb)

References

  1. 1.
    Bratton DJ, Gaisl T, Wons AM, Kohler M (2015) CPAP vs mandibular advancement devices and blood pressure in patients with obstructive sleep apnea: a systematic review and meta-analysis. JAMA 314(21):2280–2293.  https://doi.org/10.1001/jama.2015.16303 CrossRefGoogle Scholar
  2. 2.
    Liu J, Wei C, Huang L, Wang W, Liang D, Lei Z, Wang F, Wang X, Hou X, Tang X (2014) Prevalence of signs and symptoms suggestive of obstructive sleep apnea syndrome in Guangxi, China. Sleep Breath 18(2):375–382.  https://doi.org/10.1007/s11325-013-0896-2 CrossRefGoogle Scholar
  3. 3.
    Young T, Peppard PE, Gottlieb DJ (2002) Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 165(9):1217–1239CrossRefGoogle Scholar
  4. 4.
    Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, Hirano T, Adachi M (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107(8):1129–1134CrossRefGoogle Scholar
  5. 5.
    Chung S, Yoon IY, Lee CH, Kim JW (2010) The association of nocturnal hypoxemia with arterial stiffness and endothelial dysfunction in male patients with obstructive sleep apnea syndrome. Respiration 79(5):363–369.  https://doi.org/10.1159/000228905 CrossRefGoogle Scholar
  6. 6.
    Ip MS, Tse HF, Lam B, Tsang KW, Lam WK (2004) Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med 169(3):348–353.  https://doi.org/10.1164/rccm.200306-767OC CrossRefGoogle Scholar
  7. 7.
    Schwarz EI, Puhan MA, Schlatzer C, Stradling JR, Kohler M (2015) Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: a systematic review and meta-analysis. Respirology 20(6):889–895.  https://doi.org/10.1111/resp.12573 CrossRefGoogle Scholar
  8. 8.
    Vlachantoni IT, Dikaiakou E, Antonopoulos CN, Stefanadis C, Daskalopoulou SS, Petridou ET (2013) Effects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea in arterial stiffness: a meta-analysis. Sleep Med Rev 17(1):19–28.  https://doi.org/10.1016/j.smrv.2012.01.002 CrossRefGoogle Scholar
  9. 9.
    Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassai B, Erpeldinger S, Wright JM, Gueyffier F, Cornu C (2011) Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 343:d4169.  https://doi.org/10.1136/bmj.d4169 CrossRefGoogle Scholar
  10. 10.
    Deeks JJ, Higgins JPT, Altman DG (2011) Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (eds) Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, pp Available from www.cochrane-handbook.org
  11. 11.
    Deeks JJ, Higgins JPT, Altman DG (2011) Chapter 16: Special topics in statistics. In: Higgins JPT, Green S (eds) Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, pp Available from www.cochrane-handbook.org
  12. 12.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558.  https://doi.org/10.1002/sim.1186 CrossRefGoogle Scholar
  13. 13.
    Patsopoulos NA, Evangelou E, Ioannidis JP (2008) Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol 37(5):1148–1157.  https://doi.org/10.1093/ije/dyn065 CrossRefGoogle Scholar
  14. 14.
    Kritikou I, Basta M, Vgontzas AN, Pejovic S, Liao D, Tsaoussoglou M, Bixler EO, Stefanakis Z, Chrousos GP (2014) Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females. Eur Respir J 43(1):145–155.  https://doi.org/10.1183/09031936.00126712 CrossRefGoogle Scholar
  15. 15.
    Gottlieb DJ, Punjabi NM, Mehra R, Patel SR, Quan SF, Babineau DC, Tracy RP, Rueschman M, Blumenthal RS, Lewis EF, Bhatt DL, Redline S (2014) CPAP versus oxygen in obstructive sleep apnea. N Engl J Med 370(24):2276–2285.  https://doi.org/10.1056/NEJMoa1306766 CrossRefGoogle Scholar
  16. 16.
    Chirinos JA, Gurubhagavatula I, Teff K, Rader DJ, Wadden TA, Townsend R, Foster GD, Maislin G, Saif H, Broderick P, Chittams J, Hanlon AL, Pack AI (2014) CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 370(24):2265–2275.  https://doi.org/10.1056/NEJMoa1306187 CrossRefGoogle Scholar
  17. 17.
    Paz YMHL, Hazen SL, Tracy RP, Strohl KP, Auckley D, Bena J, Wang L, Walia HK, Patel SR, Mehra R (2016) Effect of continuous positive airway pressure on cardiovascular biomarkers: the sleep apnea stress randomized controlled trial. Chest 150:80–90.  https://doi.org/10.1016/j.chest.2016.03.002 CrossRefGoogle Scholar
  18. 18.
    Jones A, Vennelle M, Connell M, McKillop G, Newby DE, Douglas NJ, Riha RL (2013) 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. Sleep Med 14(12):1260–1265.  https://doi.org/10.1016/j.sleep.2013.08.786 CrossRefGoogle Scholar
  19. 19.
    Litvin AY, Sukmarova ZN, Elfimova EM, Aksenova AV, Galitsin PV, Rogoza AN, Chazova IE (2013) Effects of CPAP on “vascular” risk factors in patients with obstructive sleep apnea and arterial hypertension. Vasc Health Risk Manag 9:229–235.  https://doi.org/10.2147/vhrm.s40231 CrossRefGoogle Scholar
  20. 20.
    Povitz M, Bolo CE, Heitman SJ, Tsai WH, Wang J, James MT (2014) Effect of treatment of obstructive sleep apnea on depressive symptoms: systematic review and meta-analysis. PLoS Med 11(11):e1001762.  https://doi.org/10.1371/journal.pmed.1001762 CrossRefGoogle Scholar
  21. 21.
    Arias MA, Garcia-Rio F, Alonso-Fernandez A, Hernanz A, Hidalgo R, Martinez-Mateo V, Bartolome S, Rodriguez-Padial L (2008) CPAP decreases plasma levels of soluble tumour necrosis factor-alpha receptor 1 in obstructive sleep apnoea. Eur Respir J 32(4):1009–1015.  https://doi.org/10.1183/09031936.00007008 CrossRefGoogle Scholar
  22. 22.
    Liu X, Feng L, Cao G, Huang H, Xu Q, Yu J, Zhang S, Zhou M (2014) Cardiac structure and function improvements in coronary artery disease combined with severe obstructive sleep apnea/hypopnea syndrome patients via noninvasive positive pressure ventilation therapy. Coron Artery Dis 25(6):516–520.  https://doi.org/10.1097/mca.0000000000000129 CrossRefGoogle Scholar
  23. 23.
    Wu SQ, Liao QC, Xu XX, Sun L, Wang J, Chen R (2016) Effect of CPAP therapy on C-reactive protein and cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome. Sleep Breath.  https://doi.org/10.1007/s11325-016-1331-2
  24. 24.
    Martinez-Ceron E, Barquiel B, Bezos AM, Casitas R, Galera R, Garcia-Benito C, Hernanz A, Alonso-Fernandez A, Garcia-Rio F (2016) Effect of CPAP on glycemic control in patients with obstructive sleep apnea and type 2 diabetes. A Randomized Clinical Trial. Am J Respir Crit Care Med 194:476–485.  https://doi.org/10.1164/rccm.201510-1942OC CrossRefGoogle Scholar
  25. 25.
    Kohler M, Craig S, Pepperell JC, Nicoll D, Bratton DJ, Nunn AJ, Leeson P, Stradling JR (2013) CPAP improves endothelial function in patients with minimally symptomatic OSA: results from a subset study of the MOSAIC trial. Chest 144(3):896–902.  https://doi.org/10.1378/chest.13-0179 CrossRefGoogle Scholar
  26. 26.
    Baessler A, Nadeem R, Harvey M, Madbouly E, Younus A, Sajid H, Naseem J, Asif A, Bawaadam H (2013) Treatment for sleep apnea by continuous positive airway pressure improves levels of inflammatory markers—a meta-analysis. J Inflamm 10:13.  https://doi.org/10.1186/1476-9255-10-13 CrossRefGoogle Scholar
  27. 27.
    Xie X, Pan L, Ren D, Du C, Guo Y (2013) Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: a meta-analysis. Sleep Med 14(11):1139–1150.  https://doi.org/10.1016/j.sleep.2013.07.006 CrossRefGoogle Scholar
  28. 28.
    Lin X, Chen G, Qi J, Chen X, Zhao J, Lin Q (2016) Effect of continuous positive airway pressure on arterial stiffness in patients with obstructive sleep apnea and hypertension: a meta-analysis. Eur Arch Otorhinolaryngol.  https://doi.org/10.1007/s00405-016-3914-8
  29. 29.
    Lin YN, Zhou LN, Li QY (2017) The choice of indicators for obstructive sleep apnea treatment outcome evaluation: a matter of time-dependent response? Am J Respir Crit Care Med 196(10):1356–1357.  https://doi.org/10.1164/rccm.201705-0940LE CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Yu Ning
    • 1
  • Tian-Song Zhang
    • 2
  • Wan-Wan Wen
    • 1
  • Kun Li
    • 3
  • Yun-Xiao Yang
    • 1
  • Yan-Wen Qin
    • 4
  • Hui-Na Zhang
    • 4
  • Yun-Hui Du
    • 4
  • Lin-Yi Li
    • 4
  • Song Yang
    • 4
  • Yun-Yun Yang
    • 4
  • Miao-Miao Zhu
    • 4
  • Xiao-Lu Jiao
    • 4
  • Yan Zhang
    • 4
  • Ming Zhang
    • 1
    Email author
  • Yong-Xiang Wei
    • 3
    • 4
    Email author
  1. 1.Department of CardiologyBeijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical UniversityBeijingChina
  2. 2.Department of TCMJing’An District Centre HospitalShanghaiChina
  3. 3.Department of Otolaryngology Head & Neck SurgeryBeijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical UniversityBeijingChina
  4. 4.Key Laboratory of Upper Airway Dysfunction-related Cardiovascular DiseasesBeijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical UniversityBeijingChina

Personalised recommendations