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Endothelial dysfunction and inflammatory reactions of elderly and middle-aged men with obstructive sleep apnea syndrome

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Abstract

Introduction

Obstructive sleep apnea syndrome (OSAS) is considered to be associated with cardiovascular complications, and atherosclerosis could mediate this relationship. Cardiovascular risk factors of OSAS still need to be elucidated in elderly patients, since studies about the association between OSAS and cardiovascular diseases have been done mainly in middle-aged adults. To investigate whether endothelial dysfunction, as an early marker of atherosclerosis, and inflammatory responses in OSAS were affected by age, we studied flow-mediated dilatation (FMD) and C-reactive protein (CRP) in elderly and middle-aged patients with OSAS.

Materials and methods

This study enrolled 161 male subjects of 117 middle-aged (35–59 years old) and 44 elderly (≥60 years old) patients with OSAS. After they finished nocturnal polysomnography (NPSG), FMD was measured on the brachial artery and blood samples were obtained to determine serum CRP levels.

Results and discussion

FMD was significantly lower in the elderly patients (p = 0.04), but no difference was observed between two age groups in body mass index (BMI), neck circumference, waist-to-hip ratio, apnea hypopnea index (AHI), serum CRP level, or NPSG findings related with nocturnal hypoxemia such as average O2 saturation, percentage of time below 90% O2 saturation, and oxygen desaturation index (ODI). From the results of stepwise multiple linear regression analysis, the lowest oxygen saturation was a significant determinant of FMD (β = 0.25, p < 0.01, adjusted R 2 = 6%), and BMI (β = 0.22, p < 0.05) and waist-to-hip ratio (β = 0.21, p < 0.05) were significant variables to explain CRP (adjusted R 2 = 11%, p < 0.01) in the middle aged patients. In the elderly patients, no variable was significant for predicting FMD, but AHI was significant determinant of CRP (β = 0.46, p < 0.01, adjusted R 2 = 19%, p < 0.01). In predicting cardiovascular risks of OSAS, both hypoxia and obesity should be considered in the middle-aged group, whereas nocturnal respiratory disturbances are important in the elderly group.

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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 328:1230–1235 doi:10.1056/NEJM199304293281704

    Article  CAS  PubMed  Google Scholar 

  2. Hader C, Schroeder A, Hinz M, Micklefield GH, Rasche K (2005) Sleep disordered breathing in the elderly: comparison of women and men. J Physiol Pharmacol 56(Suppl 4):85–91

    PubMed  Google Scholar 

  3. Redline S (1998) Epidemiology of sleep-disordered breathing. Semin Respir Crit Care Med 19:113–122

    Article  Google Scholar 

  4. Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A (1998) Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med 157:144–148

    CAS  PubMed  Google Scholar 

  5. Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O (1991) Sleep-disordered breathing in community-dwelling elderly. Sleep 14:486–495

    CAS  PubMed  Google Scholar 

  6. Shamsuzzaman AS, Gersh BJ, Somers VK (2003) Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 290:1906–1914 doi:10.1001/jama.290.14.1906

    Article  CAS  PubMed  Google Scholar 

  7. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V (2005) Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 353:2034–2041 doi:10.1056/NEJMoa043104

    Article  CAS  PubMed  Google Scholar 

  8. Ancoli-Israel S, Kripke DF, Klauber MR, Fell R, Stepnowsky C, Estline E et al (1996) Morbidity, mortality and sleep-disordered breathing in community dwelling elderly. Sleep 19:277–282

    CAS  PubMed  Google Scholar 

  9. Strandberg TE, Tilvis RS (2000) C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Arterioscler Thromb Vasc Biol 20:1057–1060

    CAS  PubMed  Google Scholar 

  10. Lattimore JL, Wilcox I, Skilton M, Langenfeld M, Celermajer DS (2006) Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation. Thorax 61:491–495 doi:10.1136/thx.2004.039164

    Article  CAS  PubMed  Google Scholar 

  11. Imadojemu VA, Gleeson K, Quraishi SA, Kunselman AR, Sinoway LI, Leuenberger UA (2002) Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy. Am J Respir Crit Care Med 165:950–953

    PubMed  Google Scholar 

  12. 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 169:348–353 doi:10.1164/rccm.200306-767OC

    Article  PubMed  Google Scholar 

  13. Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB (1997) Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349:462–466 doi:10.1016/S0140-6736(96)07591-5

    Article  CAS  PubMed  Google Scholar 

  14. Guilleminault C, Kirisoglu C, Ohayon MM (2004) C-reactive protein and sleep-disordered breathing. Sleep 27:1507–1511

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Chung S, Yoon IY, Shin YK, Lee CH, Kim JW, Lee T et al (2007) Endothelial dysfunction and C-reactive protein in relation with the severity of obstructive sleep apnea syndrome. Sleep 30:997–1001

    PubMed  Google Scholar 

  17. Faulx MD, Wright AT, Hoit BD (2003) Detection of endothelial dysfunction with brachial artery ultrasound scanning. Am Heart J 145:943–951 doi:10.1016/S0002-8703(03)00097-8

    Article  PubMed  Google Scholar 

  18. Rechtschaffen A, Kales A (1968) A manual of standardized terminology, technique, and scoring system for sleep stages of human subjects. Brain Information Service/Brain Research Institute, UCLA, Los Angeles

    Google Scholar 

  19. Gould GA, Whyte KF, Rhind GB, Airlie MA, Catterall JR, Shapiro CM et al (1988) The sleep hypopnea syndrome. Am Rev Respir Dis 137:895–898

    CAS  PubMed  Google Scholar 

  20. Tatsumi K, Kasahara Y, Kurosu K, Tanabe N, Takiguchi Y, Kuriyama T (2005) Sleep oxygen desaturation and circulating leptin in obstructive sleep apnea-hypopnea syndrome. Chest 127:716–721 doi:10.1378/chest.127.3.716

    Article  PubMed  Google Scholar 

  21. Christou K, Kostikas K, Pastaka C, Tanou K, Antoniadou I, Gourgoulianis KI (2007) Nasal continuous positive airway pressure treatment reduces systemic oxidative stress in patients with severe obstructive sleep apnea syndrome. Sleep Med (in press)

  22. Kraiczi H, Caidahl K, Samuelsson A, Peker Y, Hedner J (2001) Impairment of vascular endothelial function and left ventricular filling: association with the severity of apnea-induced hypoxemia during sleep. Chest 119:1085–1091 doi:10.1378/chest.119.4.1085

    Article  CAS  PubMed  Google Scholar 

  23. Teramoto S, Kume H, Matsuse T, Ishii T, Miyashita A, Akishita M et al (2003) Oxygen administration improves the serum level of nitric oxide metabolites in patients with obstructive sleep apnea syndrome. Sleep Med 4:403–407 doi:10.1016/S1389-9457(03)00102-3

    Article  PubMed  Google Scholar 

  24. Leeman M, de Beyl VZ, Biarent D, Maggiorini M, Melot C, Naeije R (1999) Inhibition of cyclooxygenase and nitric oxide synthase in hypoxic vasoconstriction and oleic acid-induced lung injury. Am J Respir Crit Care Med 159:1383–1390

    CAS  PubMed  Google Scholar 

  25. Saletu M, Nosiska D, Kapfhammer G, Lalouschek W, Saletu B, Benesch T et al (2006) Structural and serum surrogate markers of cerebrovascular disease in obstructive sleep apnea (OSA): association of mild OSA with early atherosclerosis. J Neurol 253:746–752 doi:10.1007/s00415-006-0110-6

    Article  CAS  PubMed  Google Scholar 

  26. Lavie L (2003) Obstructive sleep apnoea syndrome–an oxidative stress disorder. Sleep Med Rev 7:35–51 doi:10.1053/smrv.2002.0261

    Article  PubMed  Google Scholar 

  27. Nieto FJ, Herrington DM, Redline S, Benjamin EJ, Robbins JA (2004) Sleep apnea and markers of vascular endothelial function in a large community sample of older adults. Am J Respir Crit Care Med 169:354–360 doi:10.1164/rccm.200306-756OC

    Article  PubMed  Google Scholar 

  28. Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A et al (2001) Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38:274–279

    CAS  PubMed  Google Scholar 

  29. Cosentino F, Osto E (2007) Aging and endothelial dysfunction. Clin Hemorheol Microcirc 37:143–147

    CAS  PubMed  Google Scholar 

  30. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772

    CAS  PubMed  Google Scholar 

  31. Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G et al (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 107:1129–1134 doi:10.1161/01.CIR.0000052627.99976.18

    Article  CAS  PubMed  Google Scholar 

  32. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P et al (2005) Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet 366:1640–1649 doi:10.1016/S0140-6736(05)67663-5

    Article  PubMed  Google Scholar 

  33. Young T, Rabago D, Zgierska A, Austin D, Laurel F (2003) Objective and subjective sleep quality in premenopausal, perimenopausal, and postmenopausal women in the Wisconsin Sleep Cohort Study. Sleep 26:667–672

    PubMed  Google Scholar 

  34. Jensen-Urstad K, Johansson J (2001) Gender difference in age-related changes in vascular function. J Intern Med 250:29–36 doi:10.1046/j.1365-2796.2001.00843.x

    Article  CAS  PubMed  Google Scholar 

  35. Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S (1994) Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 91:5212–5216 doi:10.1073/pnas.91.11.5212

    Article  CAS  PubMed  Google Scholar 

  36. Badeau M, Adlercreutz H, Kaihovaara P, Tikkanen MJ (2005) Estrogen A-ring structure and antioxidative effect on lipoproteins. J Steroid Biochem Mol Biol 96:271–278 doi:10.1016/j.jsbmb.2005.04.034

    Article  CAS  PubMed  Google Scholar 

  37. Taddei S, Virdis A, Ghiadoni L, Sudano I, Salvetti A (2000) Antihypertensive drugs and reversing of endothelial dysfunction in hypertension. Curr Hypertens Rep 2:64–70 doi:10.1007/s11906-000-0061-8

    Article  CAS  PubMed  Google Scholar 

  38. Martens FM, Visseren FL, de Koning EJ, Rabelink TJ (2005) Short-term pioglitazone treatment improves vascular function irrespective of metabolic changes in patients with type 2 diabetes. J Cardiovasc Pharmacol 46:773–778 doi:10.1097/01.fjc.0000187176.13403.05

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest statement

None of the authors have a conflict of interest to declare in relation to this work.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, South Korea

    Seockhoon Chung, In-Young Yoon, Yoon-Kyung Shin & Hee Jeong Ahn

  2. Department of Otorhinolaryngology Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, Korea

    Chul Hee Lee & Jeong-Whun Kim

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  1. Seockhoon Chung
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  2. In-Young Yoon
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Correspondence to In-Young Yoon.

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Chung, S., Yoon, IY., Shin, YK. et al. Endothelial dysfunction and inflammatory reactions of elderly and middle-aged men with obstructive sleep apnea syndrome. Sleep Breath 13, 11–17 (2009). https://doi.org/10.1007/s11325-008-0210-x

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  • DOI: https://doi.org/10.1007/s11325-008-0210-x

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