Cardiovascular Implications

  • Rakesh BhattacharjeeEmail author
  • Leila Kheirandish-Gozal
Part of the Respiratory Medicine book series (RM)


The physiological aberrations induced by obstructive sleep apnea (OSA) in children, namely the abnormalities in gas exchange, frequent cortical arousals, and fluxes of intrathoracic pressure induced by respiration in the setting of an occluded airway, can have significant ramifications of homeostasis in several organs including the cardiovascular system. In this chapter, the evidence supporting cardiovascular dysfunction in pediatric OSA is presented; prompting the hypothesis that untreated OSA may induce end-organ injury to the cardiovascular system thereby promoting long-term cardiovascular disease.


Obstructive Sleep Apnea Heart Rate Variability Continuous Positive Airway Pressure Right Ventricle Obstructive Sleep Apnea Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Funding sources: Leila Kheirandish-Gozal is supported by NIH grant K12 HL-090003.


  1. 1.
    Quan SF, Gersh BJ. Cardiovascular consequences of sleep-disordered breathing: past, present and future: report of a workshop from the National Center on Sleep Disorders Research and the National Heart, Lung, and Blood Institute. Circulation. 2004;109(8): 951–7.PubMedGoogle Scholar
  2. 2.
    Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. J Am Coll Cardiol. 2008;52(8):686–717.PubMedGoogle Scholar
  3. 3.
    Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31(8):1071–8.PubMedGoogle Scholar
  4. 4.
    Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. Sleep. 2008;31(8):1079–85.PubMedGoogle Scholar
  5. 5.
    Newman AB, Nieto FJ, Guidry U, Lind BK, Redline S, Pickering TG, et al. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol. 2001;154(1):50–9.PubMedGoogle Scholar
  6. 6.
    Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378–84.PubMedGoogle Scholar
  7. 7.
    Peled N, Abinader EG, Pillar G, Sharif D, Lavie P. Nocturnal ischemic events in patients with obstructive sleep apnea syndrome and ischemic heart disease: effects of continuous positive air pressure treatment. J Am Coll Cardiol. 1999;34(6):1744–9.PubMedGoogle Scholar
  8. 8.
    Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, et al. Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. Am J Respir Crit Care Med. 2006;173(8):910–6.PubMedGoogle Scholar
  9. 9.
    Munoz R, Duran-Cantolla J, Martinez-Vila E, Gallego J, Rubio R, Aizpuru F, et al. Severe sleep apnea and risk of ischemic stroke in the elderly. Stroke. 2006;37(9):2317–21.PubMedGoogle Scholar
  10. 10.
    Arzt M, Young T, Finn L, Skatrud JB, Bradley TD. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med. 2005;172(11):1447–51.PubMedGoogle Scholar
  11. 11.
    Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005;352(12):1206–14.PubMedGoogle Scholar
  12. 12.
    Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001;163(1):19–25.PubMedGoogle Scholar
  13. 13.
    Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96(4):1897–904.PubMedGoogle Scholar
  14. 14.
    Doherty LS, Kiely JL, Swan V, McNicholas WT. Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest. 2005;127(6):2076–84.PubMedGoogle Scholar
  15. 15.
    Milleron O, Pilliere R, Foucher A, de Roquefeuil F, Aegerter P, Jondeau G, et al. Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study. Eur Heart J. 2004;25(9): 728–34.PubMedGoogle Scholar
  16. 16.
    Gami AS, Somers VK. Obstructive sleep apnoea, metabolic syndrome, and cardiovascular outcomes. Eur Heart J. 2004;25(9):709–11.PubMedGoogle Scholar
  17. 17.
    Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165(9): 1217–39.PubMedGoogle Scholar
  18. 18.
    Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444(7121):875–80.PubMedGoogle Scholar
  19. 19.
    Wickelgren I. Obesity: how big a problem? Science. 1998;280(5368):1364–7.PubMedGoogle Scholar
  20. 20.
    Eckel RH, Kahn R, Robertson RM, Rizza RA. Preventing cardiovascular disease and diabetes: a call to action from the American Diabetes Association and the American Heart Association. Circulation. 2006;113(25):2943–6.PubMedGoogle Scholar
  21. 21.
    Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics. 1999;103(6 Pt 1):1175–82.PubMedGoogle Scholar
  22. 22.
    Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med. 2005;352(11):1138–45.PubMedGoogle Scholar
  23. 23.
    Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med. 1992;327(19):1350–5.PubMedGoogle Scholar
  24. 24.
    Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. Prevalence of high body mass index in US children and adolescents, 2007–2008. JAMA. 2010;303(3):242–9.PubMedGoogle Scholar
  25. 25.
    Gidding SS, Bao W, Srinivasan SR, Berenson GS. Effects of secular trends in obesity on coronary risk factors in children: the Bogalusa Heart Study. J Pediatr. 1995;127(6):868–74.PubMedGoogle Scholar
  26. 26.
    Morrison JA, Laskarzewski PM, Rauh JL, Brookman R, Mellies M, Frazer M, et al. Lipids, lipoproteins, and sexual maturation during adolescence: the Princeton maturation study. Metabolism. 1979;28(6): 641–9.PubMedGoogle Scholar
  27. 27.
    Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr. 1996;128(5 Pt 1):608–15.PubMedGoogle Scholar
  28. 28.
    Richards GE, Cavallo A, Meyer 3rd WJ, Prince MJ, Peters EJ, Stuart CA, et al. Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: pediatric perspective and natural history. J Pediatr. 1985;107(6):893–7.PubMedGoogle Scholar
  29. 29.
    Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med. 2002;346(11):802–10.PubMedGoogle Scholar
  30. 30.
    Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and adolescents. JAMA. 2007;298(8):874–9.PubMedGoogle Scholar
  31. 31.
    Schiel R, Beltschikow W, Kramer G, Stein G. Overweight, obesity and elevated blood pressure in children and adolescents. Eur J Med Res. 2006; 11(3):97–101.PubMedGoogle Scholar
  32. 32.
    Lurbe E, Torro I, Aguilar F, Alvarez J, Alcon J, Pascual JM, et al. Added impact of obesity and insulin resistance in nocturnal blood pressure elevation in children and adolescents. Hypertension. 2008; 51(3):635–41.PubMedGoogle Scholar
  33. 33.
    Marcus CL, Curtis S, Koerner CB, Joffe A, Serwint JR, Loughlin GM. Evaluation of pulmonary function and polysomnography in obese children and adolescents. Pediatr Pulmonol. 1996;21(3):176–83.PubMedGoogle Scholar
  34. 34.
    Gozal D, Simakajornboon N, Holbrook CR, Crabtree VM, Krishna J, Jones JH, Kheirandish-Gozal L. Secular trends in obesity and parentally reported daytime sleepiness among children referred to a pediatric sleep center for snoring and suspected sleep-disordered breathing (SDB). Sleep. 2006; 29:A74.Google Scholar
  35. 35.
    Gozal D, Kheirandish-Gozal L. The multiple challenges of obstructive sleep apnea in children: morbidity and treatment. Curr Opin Pediatr. 2008;20(6):654–8.PubMedGoogle Scholar
  36. 36.
    Dayyat E, Kheirandish-Gozal L, Gozal D. Childhood obstructive sleep apnea: one or two distinct disease entities? Sleep Med Clin. 2007;2(3):433–44.PubMedGoogle Scholar
  37. 37.
    Bhattacharjee R, Kim J, Kheirandish-Gozal L, Gozal D. Obesity and obstructive sleep apnea syndrome in children: a tale of inflammatory cascades. Pediatr Pulmonol. 2011;46(4):313–23.PubMedGoogle Scholar
  38. 38.
    Leuenberger U, Jacob E, Sweer L, Waravdekar N, Zwillich C, Sinoway L. Surges of muscle sympathetic nerve activity during obstructive apnea are linked to hypoxemia. J Appl Physiol. 1995;79(2): 581–8.PubMedGoogle Scholar
  39. 39.
    Smith ML, Niedermaier ON, Hardy SM, Decker MJ, Strohl KP. Role of hypoxemia in sleep apnea-induced sympathoexcitation. J Auton Nerv Syst. 1996;56(3): 184–90.PubMedGoogle Scholar
  40. 40.
    Imadojemu VA, Mawji Z, Kunselman A, Gray KS, Hogeman CS, Leuenberger UA. Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy. Chest. 2007;131(5):1406–13.PubMedGoogle Scholar
  41. 41.
    Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest. 1993;103(6):1763–8.PubMedGoogle Scholar
  42. 42.
    Ziegler MG, Mills PJ, Loredo JS, Ancoli-Israel S, Dimsdale JE. Effect of continuous positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea. Chest. 2001;120(3):887–93.PubMedGoogle Scholar
  43. 43.
    Imadojemu VA, Gleeson K, Gray KS, Sinoway LI, Leuenberger UA. Obstructive apnea during sleep is associated with peripheral vasoconstriction. Am J Respir Crit Care Med. 2002;165(1):61–6.PubMedGoogle Scholar
  44. 44.
    Narkiewicz K, Somers VK. Sympathetic nerve activity in obstructive sleep apnoea. Acta Physiol Scand. 2003;177(3):385–90.PubMedGoogle Scholar
  45. 45.
    Aljadeff G, Gozal D, Schechtman VL, Burrell B, Harper RM, Ward SL. Heart rate variability in children with obstructive sleep apnea. Sleep. 1997;20(2): 151–7.PubMedGoogle Scholar
  46. 46.
    Baharav A, Kotagal S, Rubin BK, Pratt J, Akselrod S. Autonomic cardiovascular control in children with obstructive sleep apnea. Clin Auton Res. 1999;9(6):345–51.PubMedGoogle Scholar
  47. 47.
    O’Brien LM, Gozal D. Autonomic dysfunction in children with sleep-disordered breathing. Sleep. 2005;28(6):747–52.PubMedGoogle Scholar
  48. 48.
    Chaicharn J, Lin Z, Chen ML, Keens TG, Davidson Ward SL, Khoo MK. Time-varying closed-loop modeling of autonomic control in pediatric obstructive sleep apnea syndrome during cold face stimulation. Conf Proc IEEE Eng Med Biol Soc. 2006;1:3569–71.PubMedGoogle Scholar
  49. 49.
    Deng ZD, Poon CS, Arzeno NM, Katz ES. Heart rate variability in pediatric obstructive sleep apnea. Conf Proc IEEE Eng Med Biol Soc. 2006;1:3565–8.PubMedGoogle Scholar
  50. 50.
    Shouldice RB, O’Brien LM, O’Brien C, de Chazal P, Gozal D, Heneghan C. Detection of obstructive sleep apnea in pediatric subjects using surface lead electrocardiogram features. Sleep. 2004;27(4):784–92.PubMedGoogle Scholar
  51. 51.
    Muzumdar HV, Sin S, Nikova M, Gates G, Kim D, Arens R. Changes in heart rate variability after adenotonsillectomy in children with obstructive sleep apnea. Chest. 2011;139(5):1050–9.PubMedGoogle Scholar
  52. 52.
    Foo JY, Lim CS. Pulse transit time as an indirect marker for variations in cardiovascular related reactivity. Technol Health Care. 2006;14(2):97–108.PubMedGoogle Scholar
  53. 53.
    O’Brien LM, Gozal D. Potential usefulness of noninvasive autonomic monitoring in recognition of arousals in normal healthy children. J Clin Sleep Med. 2007;3(1):41–7.PubMedGoogle Scholar
  54. 54.
    Tauman R, O’Brien LM, Mast BT, Holbrook CR, Gozal D. Peripheral arterial tonometry events and electroencephalographic arousals in children. Sleep. 2004;27(3):502–6.PubMedGoogle Scholar
  55. 55.
    Katz ES, Lutz J, Black C, Marcus CL. Pulse transit time as a measure of arousal and respiratory effort in children with sleep-disordered breathing. Pediatr Res. 2003;53(4):580–8.PubMedGoogle Scholar
  56. 56.
    Pillar G, Bar A, Shlitner A, Schnall R, Shefy J, Lavie P. Autonomic arousal index: an automated detection based on peripheral arterial tonometry. Sleep. 2002;25(5):543–9.PubMedGoogle Scholar
  57. 57.
    Brietzke SE, Katz ES, Roberson DW. Pulse transit time as a screening test for pediatric sleep-related breathing disorders. Arch Otolaryngol Head Neck Surg. 2007;133(10):980–4.PubMedGoogle Scholar
  58. 58.
    Foo JY, Bradley AP, Wilson SJ, Williams GR, Dakin C, Cooper DM. Screening of obstructive and central apnoea/hypopnoea in children using variability: a preliminary study. Acta Paediatr. 2006;95(5):561–4.PubMedGoogle Scholar
  59. 59.
    Pepin JL, Delavie N, Pin I, Deschaux C, Argod J, Bost M, et al. Pulse transit time improves detection of sleep respiratory events and microarousals in children. Chest. 2005;127(3):722–30.PubMedGoogle Scholar
  60. 60.
    Snow AB, Khalyfa A, Serpero LD, Capdevila OS, Kim J, Buazza MO, Gozal D. Catecholamine alterations in pediatric obstructive sleep apnea: effect of obesity. Pediatr Pulmonol. 2009;44:559–67.Google Scholar
  61. 61.
    Alexopoulos EI, Kaditis AG, Damani E, Hatzi F, Chaidas K, Kostadima E, et al. Urine catecholamines in children with obstructive sleep-disordered breathing. ATS. 2007;2007:A277.Google Scholar
  62. 62.
    Gozal D, Jortani S, Snow AB, Kheirandish-Gozal L, Bhattacharjee R, Kim J, et al. Two-dimensional differential in-gel electrophoresis proteomic approaches reveal urine candidate biomarkers in pediatric obstructive sleep apnea. Am J Respir Crit Care Med. 2009;180(12):1253–61.PubMedGoogle Scholar
  63. 63.
    Kraiczi H, Hedner J, Peker Y, Carlson J. Increased vasoconstrictor sensitivity in obstructive sleep apnea. J Appl Physiol. 2000;89(2):493–8.PubMedGoogle Scholar
  64. 64.
    Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens. 1995;8(7):657–65.PubMedGoogle Scholar
  65. 65.
    Goonasekera CD, Dillon MJ. Measurement and interpretation of blood pressure. Arch Dis Child. 2000;82(3):261–5.PubMedGoogle Scholar
  66. 66.
    Sun SS, Grave GD, Siervogel RM, Pickoff AA, Arslanian SS, Daniels SR. Systolic blood pressure in childhood predicts hypertension and metabolic syndrome later in life. Pediatrics. 2007;119(2):237–46.PubMedGoogle Scholar
  67. 67.
    Sinaiko AR. Hypertension in children. N Engl J Med. 1996;335(26):1968–73.PubMedGoogle Scholar
  68. 68.
    Ford ES, Mokdad AH, Ajani UA. Trends in risk factors for cardiovascular disease among children and adolescents in the United States. Pediatrics. 2004;114(6):1534–44.PubMedGoogle Scholar
  69. 69.
    Luepker RV, Jacobs DR, Prineas RJ, Sinaiko AR. Secular trends of blood pressure and body size in a multi-ethnic adolescent population: 1986 to 1996. J Pediatr. 1999;134(6):668–74.PubMedGoogle Scholar
  70. 70.
    Morrison JA, James FW, Sprecher DL, Khoury PR, Daniels SR. Sex and race differences in cardiovascular disease risk factor changes in schoolchildren, 1975-1990: the Princeton School Study. Am J Public Health. 1999;89(11):1708–14.PubMedGoogle Scholar
  71. 71.
    Thompson DR, Obarzanek E, Franko DL, Barton BA, Morrison J, Biro FM, et al. Childhood overweight and cardiovascular disease risk factors: the National Heart, Lung, and Blood Institute Growth and Health Study. J Pediatr. 2007;150(1):18–25.PubMedGoogle Scholar
  72. 72.
    Zintzaras E, Kaditis AG. Sleep-disordered breathing and blood pressure in children: a meta-analysis. Arch Pediatr Adolesc Med. 2007;161(2):172–8.PubMedGoogle Scholar
  73. 73.
    Marcus CL, Greene MG, Carroll JL. Blood pressure in children with obstructive sleep apnea. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1098–103.PubMedGoogle Scholar
  74. 74.
    Kohyama J, Ohinata JS, Hasegawa T. Blood pressure in sleep disordered breathing. Arch Dis Child. 2003;88(2):139–42.PubMedGoogle Scholar
  75. 75.
    Enright PL, Goodwin JL, Sherrill DL, Quan JR, Quan SF. Blood pressure elevation associated with sleep-related breathing disorder in a community sample of white and Hispanic children: the Tucson Children’s Assessment of Sleep Apnea study. Arch Pediatr Adolesc Med. 2003;157(9):901–4.PubMedGoogle Scholar
  76. 76.
    Guilleminault C, Khramsov A, Stoohs RA, Kushida C, Pelayo R, Kreutzer ML, et al. Abnormal blood pressure in prepubertal children with sleep-disordered breathing. Pediatr Res. 2004;55(1):76–84.PubMedGoogle Scholar
  77. 77.
    Kirk V, Midgley J, Giuffre M, Ronksley P, Nettel-Aguirre A, Al-Shamrani A. Hypertension and obstructive sleep apnea in Caucasian children. World J Cardiol. 2010;2(8):251–6.PubMedGoogle Scholar
  78. 78.
    O’Driscoll DM, Horne RS, Davey MJ, Hope SA, Anderson V, Trinder J, et al. Increased sympathetic activity in children with obstructive sleep apnea: Cardiovascular implications. Sleep Med. 2011;12(5):483–8.PubMedGoogle Scholar
  79. 79.
    Horne RS, Yang JS, Walter LM, Richardson HL, O’Driscoll DM, Foster AM, et al. Elevated blood pressure during sleep and wake in children with sleep-disordered breathing. Pediatrics. 2011;128(1):e85–92.PubMedGoogle Scholar
  80. 80.
    Amin RS, Carroll JL, Jeffries JL, Grone C, Bean JA, Chini B, et al. Twenty-four-hour ambulatory blood pressure in children with sleep-disordered breathing. Am J Respir Crit Care Med. 2004;169(8):950–6.PubMedGoogle Scholar
  81. 81.
    Amin R, Somers VK, McConnell K, Willging P, Myer C, Sherman M, et al. Activity-adjusted 24-hour ambulatory blood pressure and cardiac remodeling in children with sleep disordered breathing. Hypertension. 2008;51(1):84–91.PubMedGoogle Scholar
  82. 82.
    Leung LC, Ng DK, Lau MW, Chan CH, Kwok KL, Chow PY, et al. Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome. Chest. 2006;130(4):1009–17.PubMedGoogle Scholar
  83. 83.
    Soukhova-O’Hare GK, Cheng ZJ, Roberts AM, Gozal D. Postnatal intermittent hypoxia alters baroreflex function in adult rats. Am J Physiol Heart Circ Physiol. 2006;290(3):H1157–64.PubMedGoogle Scholar
  84. 84.
    Reeves SR, Guo SZ, Brittian KR, Row BW, Gozal D. Anatomical changes in selected cardio-respiratory brainstem nuclei following early post-natal chronic intermittent hypoxia. Neurosci Lett. 2006;402(3): 233–7.PubMedGoogle Scholar
  85. 85.
    Soukhova-O’Hare GK, Roberts AM, Gozal D. Impaired control of renal sympathetic nerve activity following neonatal intermittent hypoxia in rats. Neurosci Lett. 2006;399(3):181–5.PubMedGoogle Scholar
  86. 86.
    Hui AS, Striet JB, Gudelsky G, Soukhova GK, Gozal E, Beitner-Johnson D, et al. Regulation of catecholamines by sustained and intermittent hypoxia in neuroendocrine cells and sympathetic neurons. Hypertension. 2003;42(6):1130–6.PubMedGoogle Scholar
  87. 87.
    Fletcher EC, Lesske J, Behm R, Miller 3rd CC, Stauss H, Unger T. Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea. J Appl Physiol. 1992;72(5):1978–84.PubMedGoogle Scholar
  88. 88.
    Lesske J, Fletcher EC, Bao G, Unger T. Hypertension caused by chronic intermittent hypoxia—influence of chemoreceptors and sympathetic nervous system. J Hypertens. 1997;15(12 Pt 2):1593–603.PubMedGoogle Scholar
  89. 89.
    Prabhakar NR, Dick TE, Nanduri J, Kumar GK. Systemic, cellular and molecular analysis of chemoreflex-mediated sympathoexcitation by chronic intermittent hypoxia. Exp Physiol. 2007;92(1):39–44.PubMedGoogle Scholar
  90. 90.
    Fletcher EC, Bao G, Li R. Renin activity and blood pressure in response to chronic episodic hypoxia. Hypertension. 1999;34(2):309–14.PubMedGoogle Scholar
  91. 91.
    Sica AL, Greenberg HE, Ruggiero DA, Scharf SM. Chronic-intermittent hypoxia: a model of sympathetic activation in the rat. Respir Physiol. 2000;121(2–3):173–84.PubMedGoogle Scholar
  92. 92.
    Drager LF, Bortolotto LA, Figueiredo AC, Silva BC, Krieger EM, Lorenzi-Filho G. Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling. Chest. 2007;131(5):1379–86.PubMedGoogle Scholar
  93. 93.
    Alchanatis M, Tourkohoriti G, Kosmas EN, Panoutsopoulos G, Kakouros S, Papadima K, et al. Evidence for left ventricular dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J. 2002;20(5):1239–45.PubMedGoogle Scholar
  94. 94.
    Kraiczi H, Caidahl K, Samuelsson A, Peker Y, Hedner J. Impairment of vascular endothelial function and left ventricular filling: association with the severity of apnea-induced hypoxemia during sleep. Chest. 2001;119(4):1085–91.PubMedGoogle Scholar
  95. 95.
    Niroumand M, Kuperstein R, Sasson Z, Hanly PJ. Impact of obstructive sleep apnea on left ventricular mass and diastolic function. Am J Respir Crit Care Med. 2001;163(7):1632–6.PubMedGoogle Scholar
  96. 96.
    Amin RS, Kimball TR, Kalra M, Jeffries JL, Carroll JL, Bean JA, et al. Left ventricular function in children with sleep-disordered breathing. Am J Cardiol. 2005;95(6):801–4.PubMedGoogle Scholar
  97. 97.
    Amin RS, Kimball TR, Bean JA, Jeffries JL, Willging JP, Cotton RT, et al. Left ventricular hypertrophy and abnormal ventricular geometry in children and adolescents with obstructive sleep apnea. Am J Respir Crit Care Med. 2002;165(10):1395–9.PubMedGoogle Scholar
  98. 98.
    Chaouat A, Weitzenblum E, Krieger J, Oswald M, Kessler R. Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients. Chest. 1996;109(2):380–6.PubMedGoogle Scholar
  99. 99.
    Fletcher EC, Schaaf JW, Miller J, Fletcher JG. Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease. Am Rev Respir Dis. 1987;135(3):525–33.PubMedGoogle Scholar
  100. 100.
    Krieger J, Sforza E, Apprill M, Lampert E, Weitzenblum E, Ratomaharo J. Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients. Chest. 1989;96(4):729–37.PubMedGoogle Scholar
  101. 101.
    Laks L, Lehrhaft B, Grunstein RR, Sullivan CE. Pulmonary hypertension in obstructive sleep apnoea. Eur Respir J. 1995;8(4):537–41.PubMedGoogle Scholar
  102. 102.
    Podszus T, Bauer W, Mayer J, Penzel T, Peter JH, von Wichert P. Sleep apnea and pulmonary hypertension. Klin Wochenschr. 1986;64(3):131–4.PubMedGoogle Scholar
  103. 103.
    Sajkov D, Cowie RJ, Thornton AT, Espinoza HA, McEvoy RD. Pulmonary hypertension and hypoxemia in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 1994;149(2 Pt 1): 416–22.PubMedGoogle Scholar
  104. 104.
    Sajkov D, Wang T, Neill AM, Bune AJ, Saunders NA, Douglas Mcevoy R. Daytime pulmonary hemodynamics in patients with obstructive sleep apnea without lung disease. Am J Respir Crit Care Med. 1999;159(5 Pt 1):1518–26.PubMedGoogle Scholar
  105. 105.
    Tavil Y, Kanbay A, Sen N, Ciftci TU, Abaci A, Yalcin MR, et al. Comparison of right ventricular functions by tissue Doppler imaging in patients with obstructive sleep apnea syndrome with or without hypertension. Int J Cardiovasc Imaging. 2007;23(4): 469–77.PubMedGoogle Scholar
  106. 106.
    Brouillette RT, Fernbach SK, Hunt CE. Obstructive sleep apnea in infants and children. J Pediatr. 1982;100(1):31–40.PubMedGoogle Scholar
  107. 107.
    Arias MA, Garcia-Rio F, Alonso-Fernandez A, Martinez I, Villamor J. Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study. Eur Heart J. 2006;27(9):1106–13.PubMedGoogle Scholar
  108. 108.
    Sajkov D, Wang T, Saunders NA, Bune AJ, McEvoy RD. Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2002;165(2):152–8.PubMedGoogle Scholar
  109. 109.
    Sofer S, Weinhouse E, Tal A, Wanderman KL, Margulis G, Leiberman A, et al. Cor pulmonale due to adenoidal or tonsillar hypertrophy or both in children. Noninvasive diagnosis and follow-up. Chest. 1988;93(1):119–22.PubMedGoogle Scholar
  110. 110.
    Tal A, Leiberman A, Margulis G, Sofer S. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment. Pediatr Pulmonol. 1988;4(3):139–43.PubMedGoogle Scholar
  111. 111.
    Tang JR, Le Cras TD, Morris Jr KG, Abman SH. Brief perinatal hypoxia increases severity of pulmonary hypertension after reexposure to hypoxia in infant rats. Am J Physiol. 2000;278(2):L356–64.Google Scholar
  112. 112.
    Gozal D, Kheirandish-Gozal L. Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. Am J Respir Crit Care Med. 2008;177(4):369–75.PubMedGoogle Scholar
  113. 113.
    Dyugovskaya L, Lavie P, Hirsh M, Lavie L. Activated CD8+ T-lymphocytes in obstructive sleep apnoea. Eur Respir J. 2005;25(5):820–8.PubMedGoogle Scholar
  114. 114.
    Dyugovskaya L, Lavie P, Lavie L. Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med. 2002;165(7):934–9.PubMedGoogle Scholar
  115. 115.
    Dyugovskaya L, Lavie P, Lavie L. Phenotypic and functional characterization of blood gammadelta T cells in sleep apnea. Am J Respir Crit Care Med. 2003;168(2):242–9.PubMedGoogle Scholar
  116. 116.
    Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2006;174(7):824–30.PubMedGoogle Scholar
  117. 117.
    Kataoka T, Enomoto F, Kim R, Yokoi H, Fujimori M, Sakai Y, et al. The effect of surgical treatment of obstructive sleep apnea syndrome on the plasma TNF-alpha levels. Tohoku J Exp Med. 2004;204(4):267–72.PubMedGoogle Scholar
  118. 118.
    Tam CS, Wong M, McBain R, Bailey S, Waters KA. Inflammatory measures in children with obstructive sleep apnoea. J Paediatr Child Health. 2006;42(5): 277–82.PubMedGoogle Scholar
  119. 119.
    Waters KA, Mast BT, Vella S, de la Eva R, O’Brien LM, Bailey S, et al. Structural equation modeling of sleep apnea, inflammation, and metabolic dysfunction in children. J Sleep Res. 2007;16(4):388–95.PubMedGoogle Scholar
  120. 120.
    Gozal D, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Khalyfa A, Tauman R. Sleep measures and morning plasma TNF-alpha levels in children with sleep-disordered breathing. Sleep. 2010;33(3):319–25.PubMedGoogle Scholar
  121. 121.
    Serpero LD, Kheirandish-Gozal L, Tauman R, Sans Capdevila O, Gozal D. Sleep fragmentation and circulating TNF alpha levels in children with sleep-disordered breathing. Proc Am Thor Soc. 2006;3:A555.Google Scholar
  122. 122.
    Khalyfa A, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Gozal D. TNF-alpha gene polymorphisms and excessive daytime sleepiness in pediatric obstructive sleep apnea. J Pediatr. 2011;158(1):77–82.PubMedGoogle Scholar
  123. 123.
    Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836–43.PubMedGoogle Scholar
  124. 124.
    Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557–65.PubMedGoogle Scholar
  125. 125.
    Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102(18): 2165–8.PubMedGoogle Scholar
  126. 126.
    Can M, Acikgoz S, Mungan G, Bayraktaroglu T, Kocak E, Guven B, et al. Serum cardiovascular risk factors in obstructive sleep apnea. Chest. 2006;129(2):233–7.PubMedGoogle Scholar
  127. 127.
    Chung S, Yoon IY, Shin YK, Lee CH, Kim JW, Lee T, et al. Endothelial dysfunction and C-reactive protein in relation with the severity of obstructive sleep apnea syndrome. Sleep. 2007;30(8):997–1001.PubMedGoogle Scholar
  128. 128.
    Friedman M, Bliznikas D, Vidyasagar R, Woodson BT, Joseph NJ. Reduction of C-reactive protein with surgical treatment of obstructive sleep apnea hypopnea syndrome. Otolaryngol Head Neck Surg. 2006;135(6):900–5.PubMedGoogle Scholar
  129. 129.
    Kageyama N, Nomura M, Nakaya Y, Watanabe T, Ito S. Relationship between adhesion molecules with hs-CRP and changes therein after ARB (Valsartan) administration in patients with obstructive sleep apnea syndrome. J Med Invest. 2006;53(1–2):134–9.PubMedGoogle Scholar
  130. 130.
    Minoguchi K, Yokoe T, Tanaka A, Ohta S, Hirano T, Yoshino G, et al. Association between lipid peroxidation and inflammation in obstructive sleep apnoea. Eur Respir J. 2006;28(2):378–85.PubMedGoogle Scholar
  131. 131.
    Minoguchi K, Yokoe T, Tazaki T, Minoguchi H, Tanaka A, Oda N, et al. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med. 2005;172(5):625–30.PubMedGoogle Scholar
  132. 132.
    Punjabi NM, Beamer BA. C-reactive protein is associated with sleep disordered breathing independent of adiposity. Sleep. 2007;30(1):29–34.PubMedGoogle Scholar
  133. 133.
    Saletu M, Nosiska D, Kapfhammer G, Lalouschek W, Saletu B, Benesch T, et al. Structural and serum surrogate markers of cerebrovascular disease in obstructive sleep apnea (OSA): association of mild OSA with early atherosclerosis. J Neurol. 2006;253(6):746–52.PubMedGoogle Scholar
  134. 134.
    Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation. 2002;105(21):2462–4.PubMedGoogle Scholar
  135. 135.
    Zouaoui Boudjeltia K, Van Meerhaeghe A, Doumit S, Guillaume M, Cauchie P, Brohee D, et al. Sleep apnoea-hypopnoea index is an independent predictor of high-sensitivity C-reactive protein elevation. Respiration. 2006;73(2):243–6.PubMedGoogle Scholar
  136. 136.
    Larkin EK, Rosen CL, Kirchner HL, Storfer-Isser A, Emancipator JL, Johnson NL, et al. Variation of C-reactive protein levels in adolescents: association with sleep-disordered breathing and sleep duration. Circulation. 2005;111(15):1978–84.PubMedGoogle Scholar
  137. 137.
    Tauman R, Ivanenko A, O’Brien LM, Gozal D. Plasma C-reactive protein levels among children with sleep-disordered breathing. Pediatrics. 2004;113(6):e564–9.PubMedGoogle Scholar
  138. 138.
    Tauman R, O’Brien LM, Gozal D. Hypoxemia and obesity modulate plasma C-reactive protein and interleukin-6 levels in sleep-disordered breathing. Sleep Breath. 2007;11(2):77–84.PubMedGoogle Scholar
  139. 139.
    Kheirandish-Gozal L, Capdevila OS, Tauman R, Gozal D. Plasma C-reactive protein in nonobese children with obstructive sleep apnea before and after adenotonsillectomy. J Clin Sleep Med. 2006;2(3):301–4.PubMedGoogle Scholar
  140. 140.
    Li AM, Chan MH, Yin J, So HK, Ng SK, Chan IH, et al. C-reactive protein in children with obstructive sleep apnea and the effects of treatment. Pediatr Pulmonol. 2008;43(1):34–40.PubMedGoogle Scholar
  141. 141.
    Barcelo A, Barbe F, Llompart E, Mayoralas LR, Ladaria A, Bosch M, et al. Effects of obesity on C-reactive protein level and metabolic disturbances in male patients with obstructive sleep apnea. Am J Med. 2004;117(2):118–21.PubMedGoogle Scholar
  142. 142.
    Guilleminault C, Kirisoglu C, Ohayon MM. C-reactive protein and sleep-disordered breathing. Sleep. 2004;27(8):1507–11.PubMedGoogle Scholar
  143. 143.
    Kaditis AG, Alexopoulos EI, Kalampouka E, Kostadima E, Germenis A, Zintzaras E, et al. Morning levels of C-reactive protein in children with obstructive sleep-disordered breathing. Am J Respir Crit Care Med. 2005;171(3):282–6.PubMedGoogle Scholar
  144. 144.
    Ryan S, Nolan GM, Hannigan E, Cunningham S, Taylor C, McNicholas WT. Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity. Thorax. 2007;62(6): 509–14.PubMedGoogle Scholar
  145. 145.
    Sharma SK, Mishra HK, Sharma H, Goel A, Sreenivas V, Gulati V, et al. Obesity, and not obstructive sleep apnea, is responsible for increased serum hs-CRP levels in patients with sleep-disordered breathing in Delhi. Sleep Med. 2008;9(2):149–56.PubMedGoogle Scholar
  146. 146.
    Taheri S, Austin D, Lin L, Nieto FJ, Young T, Mignot E. Correlates of serum C-reactive protein (CRP)—no association with sleep duration or sleep disordered breathing. Sleep. 2007;30(8):991–6.PubMedGoogle Scholar
  147. 147.
    Baldwin CM, Bootzin RR, Schwenke DC, Quan SF. Antioxidant nutrient intake and supplements as potential moderators of cognitive decline and cardiovascular disease in obstructive sleep apnea. Sleep Med Rev. 2005;9(6):459–76.PubMedGoogle Scholar
  148. 148.
    Gozal D, Kheirandish L. Oxidant stress and inflammation in the snoring child: confluent pathways to upper airway pathogenesis and end-organ morbidity. Sleep Med Rev. 2006;10(2):83–96.PubMedGoogle Scholar
  149. 149.
    Khalyfa A, Bhushan B, Hegazi M, Kim J, Kheirandish-Gozal L, Bhattacharjee R, et al. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels. Lipids Health Dis. 2010;9:18.PubMedGoogle Scholar
  150. 150.
    Gozal D, Crabtree VM, Sans Capdevila O, Witcher LA, Kheirandish-Gozal L. C-reactive protein, obstructive sleep apnea, and cognitive dysfunction in school-aged children. Am J Respir Crit Care Med. 2007;176(2):188–93.PubMedGoogle Scholar
  151. 151.
    Lavie L, Dyugovskaya L, Lavie P. Sleep-apnea-related intermittent hypoxia and atherogenesis: adhesion molecules and monocytes/endothelial cells interactions. Atherosclerosis. 2005;183(1):183–4.PubMedGoogle Scholar
  152. 152.
    Chin K, Nakamura T, Shimizu K, Mishima M, Nakamura T, Miyasaka M, et al. Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome. Am J Med. 2000;109(7):562–7.PubMedGoogle Scholar
  153. 153.
    El-Solh AA, Mador MJ, Sikka P, Dhillon RS, Amsterdam D, Grant BJ. Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea. Chest. 2002;121(5):1541–7.PubMedGoogle Scholar
  154. 154.
    Ohga E, Nagase T, Tomita T, Teramoto S, Matsuse T, Katayama H, et al. Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome. J Appl Physiol. 1999;87(1):10–4.PubMedGoogle Scholar
  155. 155.
    O’Brien LM, Serpero LD, Tauman R, Gozal D. Plasma adhesion molecules in children with sleep-disordered breathing. Chest. 2006;129(4):947–53.PubMedGoogle Scholar
  156. 156.
    Kaditis AG, Alexopoulos EI, Kalampouka E, Hatzi F, Karadonta I, Kyropoulos T, et al. Nocturnal change of circulating intercellular adhesion molecule 1 levels in children with snoring. Sleep Breath. 2007;11(4):267–74.PubMedGoogle Scholar
  157. 157.
    Gozal D, Sans Capdevila O, Kheirandish-Gozal L. Metabolic alterations in obstructive sleep apnea among non-obese and obese prepubertal children. Am J Respir Crit Care Med. 2008;177:1142–9.Google Scholar
  158. 158.
    Rammes A, Roth J, Goebeler M, Klempt M, Hartmann M, Sorg C. Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. J Biol Chem. 1997;272(14):9496–502.PubMedGoogle Scholar
  159. 159.
    Guignard F, Mauel J, Markert M. Phosphorylation of myeloid-related proteins MRP-14 and MRP-8 during human neutrophil activation. Eur J Biochem. 1996;241(1):265–71.PubMedGoogle Scholar
  160. 160.
    Croce K, Gao H, Wang Y, Mooroka T, Sakuma M, Shi C, et al. Myeloid-related protein-8/14 is critical for the biological response to vascular injury. Circulation. 2009;120(5):427–36.PubMedGoogle Scholar
  161. 161.
    Ionita MG, Vink A, Dijke IE, Laman JD, Peeters W, van der Kraak PH, et al. High levels of myeloid-related protein 14 in human atherosclerotic plaques correlate with the characteristics of rupture-prone lesions. Arterioscler Thromb Vasc Biol. 2009;29(8): 1220–7.PubMedGoogle Scholar
  162. 162.
    Altwegg LA, Neidhart M, Hersberger M, Muller S, Eberli FR, Corti R, et al. Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes. Eur Heart J. 2007;28(8):941–8.PubMedGoogle Scholar
  163. 163.
    Kim J, Bhattacharjee R, Snow AB, Capdevila OS, Kheirandish-Gozal L, Gozal D. Myeloid-related protein 8/14 levels in children with obstructive sleep apnoea. Eur Respir J. 2010;35(4):843–50.PubMedGoogle Scholar
  164. 164.
    Bokinsky G, Miller M, Ault K, Husband P, Mitchell J. Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation. Chest. 1995;108(3): 625–30.PubMedGoogle Scholar
  165. 165.
    Nobili L, Schiavi G, Bozano E, De Carli F, Ferrillo F, Nobili F. Morning increase of whole blood viscosity in obstructive sleep apnea syndrome. Clin Hemorheol Microcirc. 2000;22(1):21–7.PubMedGoogle Scholar
  166. 166.
    Rangemark C, Hedner JA, Carlson JT, Gleerup G, Winther K. Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients. Sleep. 1995;18(3):188–94.PubMedGoogle Scholar
  167. 167.
    Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax. 2004;59(9):777–82.PubMedGoogle Scholar
  168. 168.
    von Kanel R, Loredo JS, Ancoli-Israel S, Dimsdale JE. Association between sleep apnea severity and blood coagulability: treatment effects of nasal continuous positive airway pressure. Sleep Breath. 2006;10(3):139–46.Google Scholar
  169. 169.
    Wessendorf TE, Thilmann AF, Wang YM, Schreiber A, Konietzko N, Teschler H. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med. 2000;162(6):2039–42.PubMedGoogle Scholar
  170. 170.
    Kaditis AG, Alexopoulos EI, Kalampouka E, Kostadima E, Angelopoulos N, Germenis A, et al. Morning levels of fibrinogen in children with sleep-disordered breathing. Eur Respir J. 2004;24(5): 790–7.PubMedGoogle Scholar
  171. 171.
    Kheirandish-Gozal L, Bhattacharjee R, Gozal D. Autonomic alterations and endothelial dysfunction in pediatric obstructive sleep apnea. Sleep Med. 2010;11(7):714–20.PubMedGoogle Scholar
  172. 172.
    Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, et al. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 2000;102(21):2607–10.PubMedGoogle Scholar
  173. 173.
    Nieto FJ, Herrington DM, Redline S, Benjamin EJ, Robbins JA. Sleep apnea and markers of vascular endothelial function in a large community sample of older adults. Am J Respir Crit Care Med. 2004;169(3):354–60.PubMedGoogle Scholar
  174. 174.
    Oflaz H, Cuhadaroglu C, Pamukcu B, Meric M, Ece T, Kasikcioglu E, et al. Endothelial function in patients with obstructive sleep apnea syndrome but without hypertension. Respiration. 2006;73(6):751–6.PubMedGoogle Scholar
  175. 175.
    Ip MS, Tse HF, Lam B, Tsang KW, Lam WK. Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med. 2004;169(3):348–53.PubMedGoogle Scholar
  176. 176.
    Lattimore JL, Wilcox I, Skilton M, Langenfeld M, Celermajer DS. Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation. Thorax. 2006;61(6):491–5.PubMedGoogle Scholar
  177. 177.
    Ohike Y, Kozaki K, Iijima K, Eto M, Kojima T, Ohga E, et al. Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure–possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine. Circ J. 2005;69(2):221–6.PubMedGoogle Scholar
  178. 178.
    Itzhaki S, Dorchin H, Clark G, Lavie L, Lavie P, Pillar G. The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function. Chest. 2007;131(3):740–9.PubMedGoogle Scholar
  179. 179.
    Itzhaki S, Wertheimer E. Metabolism of adipose tissue in vitro: nutritional factors and effect of insulin. Endocrinology. 1957;61(1):72–8.PubMedGoogle Scholar
  180. 180.
    de la Pena M, Barcelo A, Barbe F, Pierola J, Pons J, Rimbau E, et al. Endothelial function and circulating endothelial progenitor cells in patients with sleep apnea syndrome. Respiration. 2007;76:28–32.Google Scholar
  181. 181.
    Gozal D, Lipton AJ, Jones KL. Circulating vascular endothelial growth factor levels in patients with obstructive sleep apnea. Sleep. 2002;25(1):59–65.PubMedGoogle Scholar
  182. 182.
    Suheyl Ezgu F, Hasanoglu A, Tumer L, Ozbay F, Aybay C, Gunduz M. Endothelial activation and inflammation in prepubertal obese Turkish children. Metabolism. 2005;54(10):1384–9.PubMedGoogle Scholar
  183. 183.
    Valle Jimenez M, Estepa RM, Camacho RM, Estrada RC, Luna FG, Guitarte FB. Endothelial dysfunction is related to insulin resistance and inflammatory biomarker levels in obese prepubertal children. Eur J Endocrinol. 2007;156(4):497–502.PubMedGoogle Scholar
  184. 184.
    Giannini C, de Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML, Chiarelli F, et al. Obese related effects of inflammatory markers and insulin resistance on increased carotid intima media thickness in pre-pubertal children. Atherosclerosis. 2008;197(1): 448–56.PubMedGoogle Scholar
  185. 185.
    Huang K, Zou CC, Yang XZ, Chen XQ, Liang L. Carotid intima-media thickness and serum endothelial marker levels in obese children with metabolic syndrome. Arch Pediatr Adolesc Med. 2010;164(9):846–51.PubMedGoogle Scholar
  186. 186.
    Shachor-Meyouhas Y, Pillar G, Shehadeh N. Uncontrolled type 1 diabetes mellitus and endothelial dysfunction in adolescents. Isr Med Assoc J. 2007;9(9):637–40.PubMedGoogle Scholar
  187. 187.
    DiMeglio LA, Tosh A, Saha C, Estes M, Mund J, Mead LE, et al. Endothelial abnormalities in adolescents with type 1 diabetes: a biomarker for vascular sequelae? J Pediatr. 2010;157(4):540–6.PubMedGoogle Scholar
  188. 188.
    Trigona B, Aggoun Y, Maggio A, Martin XE, Marchand LM, Beghetti M, et al. Preclinical noninvasive markers of atherosclerosis in children and adolescents with type 1 diabetes are influenced by physical activity. J Pediatr. 2010;157(4):533–9.PubMedGoogle Scholar
  189. 189.
    Short KR, Blackett PR, Gardner AW, Copeland KC. Vascular health in children and adolescents: effects of obesity and diabetes. Vasc Health Risk Manag. 2009;5:973–90.PubMedGoogle Scholar
  190. 190.
    Bhattacharjee R, Alotaibi WH, Kheirandish-Gozal L, Capdevila OS, Gozal D. Endothelial dysfunction in obese non-hypertensive children without evidence of sleep disordered breathing. BMC Pediatr. 2010;10:8.PubMedGoogle Scholar
  191. 191.
    Gozal D, Kheirandish-Gozal L, Sans Capdevila O, Serpero LD, Dayyat E. Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy. Circulation. 2007;116(20):2307–14.PubMedGoogle Scholar
  192. 192.
    Bhattacharjee R, Kim J, Alotaibi WH, Kheirandish-Gozal L, Capdevila OS, Gozal D. Endothelial dysfunction in non-hypertensive children: potential contributions of obesity and obstructive sleep apnea. Chest. 2011;141:682–791.Google Scholar
  193. 193.
    Dubern B, Aggoun Y, Boule M, Fauroux B, Bonnet D, Tounian P. Arterial alterations in severely obese children with obstructive sleep apnoea. Int J Pediatr Obes. 2010;5(3):230–6.PubMedGoogle Scholar
  194. 194.
    Kelly AS, Hebbel RP, Solovey AN, Schwarzenberg SJ, Metzig AM, Moran A, et al. Circulating activated endothelial cells in pediatric obesity. J Pediatr. 2010;157(4):547–51.PubMedGoogle Scholar
  195. 195.
    Kheirandish-Gozal L, Bhattacharjee R, Kim J, Clair HB, Gozal D. Endothelial progenitor cells and vascular dysfunction in children with obstructive sleep apnea. Am J Respir Crit Care Med. 2010;182(1): 92–7.PubMedGoogle Scholar
  196. 196.
    Kim J, Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, Gozal D. Circulating microparticles in children with sleep disordered breathing. Chest. 2011;140(2):408–17.Google Scholar
  197. 197.
    Kim J, Bhattacharjee R, Snow AB, Capdevila OS, Kheirandish-Gozal L, Gozal D. Myeloid related protein 8/14 levels in children with obstructive sleep apnoea. Eur Respir J. 2009;35(4):843–50.Google Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Divisions of Pulmonary and Sleep Medicine, Department of PediatricsThe University of ChicagoChicagoUSA
  2. 2.Section of Sleep Medicine, Department of Pediatrics, Pritzker School of MedicineThe University of ChicagoChicagoUSA

Personalised recommendations