Skip to main content
Log in

The Impact of CPAP on Cardiovascular Biomarkers in Minimally Symptomatic Patients with Obstructive Sleep Apnea: A Pilot Feasibility Randomized Crossover Trial

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Background Previous, largely uncontrolled studies demonstrated the substantial effects of continuous positive airway pressure ventilation (CPAP) on a variety of physiologic and biochemical markers known to be risk factors for cardiovascular disease in patients with obstructive sleep apnea (OSA). In this pilot crossover study, we assessed (1) the feasibility of using CPAP in a group of minimally symptomatic patients with OSA, assessed through patient compliance and (2) CPAP therapy’s effect on biomarkers in these patients. Methods We studied patients with minimal daytime sleepiness who were referred to the University of British Columbia’s Hospital Sleep Clinic with suspected OSA and an apnea-hypopnea index (AHI) > 15 events/h. Patients were randomized to either CPAP or no therapy for 4 weeks followed by a washout of 4 weeks, and then a crossover to the other intervention. Fasting morning blood and urine, 24-h blood pressure (BP) measurements, and endothelial function (peak flow-mediated dilation to nitroglycerin-mediated dilation ratio) were assessed before and after each study intervention. Results Nine adult male and four female patients were studied. Mean (SD) age was 55 (7) years, mean AHI = 27.9/h, mean Epworth Sleepiness Score = 6.8 (11/13 had a score < 10), and mean BMI = 31.1 kg/m2. Mean compliance with CPAP therapy was 5.53 h/night. Compared to no therapy, potential improvements were observed with CPAP for urinary microalbumin, norepinephrine, and epinephrine to creatinine ratios (decreased by 3.51 mg/mmol, 1.70 nmol/mmol, and 0.95 nmol/mmol, respectively); 24-h BP (systolic decreased by 3.60 mmHg, diastolic by 0.70 mmHg); homeostasis model for insulin resistance score (decreased by 1.11); and endothelial function (increased by 7.4%). However, none of the above differences was significant (p > 0.10). Conclusion In this pilot study there were potential improvements in a variety of cardiovascular biomarkers with CPAP. CPAP compliance was reasonably good even though patients were not particularly sleepy. Accordingly, larger randomized controlled trials in this area appear feasible and warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 32:1230–1235. doi:10.1056/NEJM199304293281704

    Article  Google Scholar 

  2. Ip M, Chung KF, Chan KN, Lam SP, Lee K (1999) Previously unrecognized obstructive sleep apnea in Chinese subjects with essential hypertension. Lung 177(6):391–400. doi:10.1007/PL00007656

    Article  PubMed  CAS  Google Scholar 

  3. AlGhanim N, Comondore V, Ayas NT (2008) The economic impact of obstructive sleep apnea. Lung 186:7–12. doi:10.1007/s00408-007-9055-5

    Article  PubMed  Google Scholar 

  4. Marin JM, Carrizo SJ, Vincente E, Agusti AG (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053

    PubMed  Google Scholar 

  5. Szollosi I, Krum H, Kaye D, Naughton MT (2007) Sleep apnea in heart failure increases heart rate variability and sympathetic dominance. Sleep 30(1):1509–1514

    PubMed  Google Scholar 

  6. Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, Somers VK (2002) Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 105(21):2462–2464. doi:10.1161/01.CIR.0000018948.95175.03

    Article  PubMed  CAS  Google Scholar 

  7. Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, Somers VK (2000) Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 102(21):2607–2610

    PubMed  CAS  Google Scholar 

  8. Zamarron C, Ricoy J, Riveiro A, Gude F (2008) Plasminogen activator inhibitor 1 in obstructive sleep apnea patients with and without hypertension. Lung 186(3):151–156

    Article  PubMed  CAS  Google Scholar 

  9. Budhiraja R, Parthasarathy S, Quan SF (2007) Endothelial dysfunction in obstructive sleep apnea. J Clin Sleep Med 3(4):409–415

    PubMed  Google Scholar 

  10. Fleetham J, Ayas N, Bradley D, Ferguson K, Fitzpatrick M, George C, Hanly P, Hill F, Kimoff J, Kryger M, Morrison D, Series F, Tsai W, CTS Sleep Disordered Breathing Committee (2006) Canadian thoracic society guidelines: diagnosis and treatment of sleep disordered breathing in adults. Can Respir J 13(7):387–392

    PubMed  Google Scholar 

  11. Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT (2003) Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med 163:565–571. doi:10.1001/archinte.163.5.565

    Article  PubMed  Google Scholar 

  12. Mulgrew AT, Fox N, Ayas NT, Ryan CF (2007) Diagnosis and initial management of OSA without polysomnography: a randomized validation study. Ann Intern Med 146:157–166

    PubMed  Google Scholar 

  13. Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A (2003) The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol 42(6):1037–1043. doi:10.1016/S0735-1097(03)00927-6

    Article  PubMed  CAS  Google Scholar 

  14. Rosner B (1995) Fundamentals of Biostatistics, 4th edn. Duxbury Press, Boston, MA, pp 564–565

    Google Scholar 

  15. Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH (2003) Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 107(1):68–73. doi:10.1161/01.CIR.0000042706.47107.7A

    Article  PubMed  Google Scholar 

  16. Campos-Rodriguez F, Grilo-Reina A, Perez-Ronchel J, Merino-Sanchez M, Gonzalez-Benitez MA, Beltran-Robles M, Almeida-Gonzalez C (2006) Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: a placebo-controlled trial. Chest 129(6):1457–1467. doi:10.1378/chest.129.6.1459

    Article  Google Scholar 

  17. Alajmi M, Mulgrew AT, Fox J, Davidson W, Schulzer M, Mak E, Ryan CF, Fleetham J, Choi P, Ayas NT (2007) Impact of CPAP therapy on blood pressure in patients with OSAH. A meta-analysis of RCT. Lung 185:67–72. doi:10.1007/s00408-006-0117-x

    CAS  Google Scholar 

  18. Haentjens P, Van Meerhaeghe A, Moscariello A, De Weerdt S, Poppe K, Dupont A, Velkeniers B (2007) The impact of CPAP on blood pressure in patients with obstructive sleep apnea syndrome. Arch Intern Med 167:757–764. doi:10.1001/archinte.167.8.757

    Article  PubMed  Google Scholar 

  19. Ridker PM (2003) High-sensitivity C-reactive protein and cardiovascular risk: rationale for screening and primary prevention. Am J Cardiol 92(4B):17K–22K. doi:10.1016/S0002-9149(03)00774-4

    Article  PubMed  CAS  Google Scholar 

  20. 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):1129–1134. doi:10.1161/01.CIR.0000052627.99976.18

    Article  PubMed  CAS  Google Scholar 

  21. Barcelo A, Barbe F, Llompart E, Mayoralas LR, Ladaria A, Bosch M, Agustí AG (2004) Effects of obesity on C-reactive protein level and metabolic disturbances in male patients with obstructive sleep apnea. Am J Med 117(2):118–121. doi:10.1016/j.amjmed.2004.01.025

    Article  PubMed  CAS  Google Scholar 

  22. Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, Marino RL, Rodriguez A, Hubbard WC, O’Donnell CP, Polotsky VY (2005) Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 97:698. doi:10.1161/01.RES.0000183879.60089.a9

    Article  PubMed  CAS  Google Scholar 

  23. Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR (2004) Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 59(9):777–782. doi:10.1136/thx.2003.018739

    Article  PubMed  CAS  Google Scholar 

  24. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL (2002) Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 165:677–682

    PubMed  Google Scholar 

  25. Harsch IA, Schahin SP, Radespiel-Troger M, Weintz O, Jahreiss H, Fuchs FS, Wiest GH, Hahn EG, Lohmann T, Konturek PC, Ficker JH (2004) Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med 169(2):156–162. doi:10.1164/rccm.200302-206OC

    Article  PubMed  Google Scholar 

  26. West SD, Nicoll DJ et al (2007) The effect of CPAP on insulin resistance and HbA1C in men with OSA and type 2 diabetes. Thorax 62(11):969–974

    Article  PubMed  Google Scholar 

  27. Steiropoulos P, Tsara V, Nena E, Fitili C, Kataropoulou M, Froudarakis M, Christaki P, Bouros D (2008) Effect of continuous positive airway pressure treatment on serum cardiovascular risk factors in patients with obstructive sleep apnea-hypopnea syndrome. Chest 132(3):843–851

    Article  Google Scholar 

  28. Robinson GV, Smith DM, Langford BA, Davies RJ, Stradling JR (2006) CPAP does not reduce blood pressure in non-sleepy hypertensive OSA patients. Eur Respira J 27:1229–1235

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Dr. Ayas was supported by a Michael Smith Foundation Health Research (MSFHR) Scholar Award and a Departmental Scholar Award from the University of British Columbia (UBC). This work was supported by an Infrastructure Grant (Sleep Disordered Breathing) from the MSFHR, and a research grant from the Vancouver General Hospital/UBC Hospital Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Najib T. Ayas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Comondore, V.R., Cheema, R., Fox, J. et al. The Impact of CPAP on Cardiovascular Biomarkers in Minimally Symptomatic Patients with Obstructive Sleep Apnea: A Pilot Feasibility Randomized Crossover Trial. Lung 187, 17–22 (2009). https://doi.org/10.1007/s00408-008-9115-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-008-9115-5

Keywords

Navigation