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Obstructive sleep apnea and cardiovascular comorbidity: common pathophysiological mechanisms to cardiovascular disease

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Obstructive sleep apnea (OSA) is associated with many cardiovascular and metabolic diseases. Sleep apnea causes intermittent hypoxemia, chest pressure fluctuations and a reaction from the cerebral cortex in the form of a short awakening during sleep (EEG-activation). The consequences of pathological pathways are studied in experimental models involving cell cultures, animals, and healthy volunteers. At present, the negative impact of intermittent hypoxemia on a variety of pathophysiological disorders of the heart and blood vessels (vascular tone fluctuations, thickening of the intimamedia complex in the vascular wall, direct damaging effect on the myocardium) has a great evidence base. Two other pathological components of OSA (pressure fluctuations and EEG-activation) can also affect cardiovascular system, mainly affecting the increase in blood pressure and changing cardiac hemodynamics. Although these reactions are considered separately in the review, with the development of sleep apnea they occur sequentially and are closely interrelated. As a result, these pathological pathways trigger further pathophysiological mechanisms acting on the heart and blood vessels. It is known that these include excessive sympathetic activation, inflammation, oxidative stress and metabolic dysregulation. In many respects being links of one process, these mechanisms can trigger damage to the vascular wall, contributing to the formation of atherosclerotic lesions. The accumulated data with varying degrees of reliability confirm the participation of OSA through these processes in the formation of cardiovascular disorders. There are factors limiting direct evidence of this interaction (sleep deprivation, causing similar changes, as well as the inability to share the contribution of other risk factors for cardiovascular diseases, in particular arterial hypertension, obesity, which are often associated with OSA). It is necessary to continue the study of processes that implement the pathological effect of OSA on the cardiovascular system.

About the Authors

M. V. Agaltsov
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Michail V. Agaltsov 


O. M. Drapkina
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Oxana M. Drapkina

eLibrary SPIN 4456-1297



1. Javaheri S, Barbe F, Campos-Rodriguez F, et al. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences. J Am Coll Cardiol. 2017;69(7):841-58. DOI:10.1016/j.jacc.2016.11.069.

2. Peppard PE, Young T, Barnet JH, et al. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006-14. DOI:10.1093/aje/kws342.

3. Heinzer R, Vat S, Marques-Vidal P, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015;3(4):310-18. DOI:10.1016/S22132600(15)00043-0.

4. Kent BD, Grote L, Ryan S, et al. Diabetes mellitus prevalence and control in sleep-disordered breathing: the European Sleep Apnea Cohort (ESADA) study. Chest. 2014;146(4):982-90. DOI:10.1378/chest.13-2403.

5. McNicholas WT, Bonsignore MR. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J. 2007;29(1):156-78. DOI:10.1183/09031936.00027406.

6. Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern Med. 2005;142(3):187-97. DOI:10.7326/0003-4819-142-3-200502010-00010.

7. Almendros I, Wang Y, Gozal D. The polymorphic and contradictory aspects of intermittent hypoxia. Am J Physiol Lung Cell Mol Physiol. 2014;307(2):129-40. DOI:10.1152/ajplung.00089.2014.

8. Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia-revisited the bad ugly and good: implications to the heart and brain. Sleep Med Rev. 2015;20:27-45. DOI:10.1016/j.smrv.2014.07.003.

9. Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ. 2000;320(7233):479-82. DOI:10.1136/bmj.320.7233.479.

10. Baguet JP, Hammer L, Levy P, et al. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest. 2005;128(5):3407-12. DOI:10.1378/chest.128.5.3407

11. Foster GE, Hanly PJ, Ahmed SB, et al. Intermittent hypoxia increases arterial blood pressure in humans through a renin-angiotensin system-dependent mechanism. Hypertension. 2010;56(3):369-77. DOI:10.1161/HYPERTENSIONAHA.110.152108.

12. Tkacova R, McNicholas WT, Javorsky M, et al. Nocturnal intermittent hypoxia predicts prevalent hypertension in the European Sleep Apnoea Database cohort study. Eur Respir J. 2014;44(4):931-41. DOI:10.1183/09031936.00225113.

13. Fletcher EC, Lesske J, Qian W, et al. Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats. Hypertension. 1992;19(6Pt1):555-61. DOI:10.1161/01.hyp.19.6.555.

14. Hamrahi H, Chan B, Horner RL. On-line detection of sleep-wake states and application to produce intermittent hypoxia only in sleep in rats. J Appl Physiol. 2001;90(6):2130-40. DOI:10.1152/jappl.2001.90.6.2130.

15. Tamisier R, Gilmartin GS, Launois SH, et al. A new model of chronic intermittent hypoxia in humans:effect on ventilation, sleep, and blood pressure. J Appl Physiol. 2009;107(1):17-24. DOI:10.1152/japplphysiol.91165.2008.

16. Lin M, Liu R, Gozal D, et al. Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice. Am J Physiol Heart Circ Physiol. 2007;293(2):H 997-1006. DOI:10.1152/ajpheart.01124.2006.

17. Lai CJ, Yang CC, Hsu YY, et al. Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats. J Appl Physiol. 2006;100(6):1974-82. DOI:10.1152/japplphysiol.01051.2005.

18. Tamisier R, Pepin JL, Remy J, et al. 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011;37(1):119-28. DOI:10.1183/09031936.00204209.

19. Arnaud C, Beguin PC, Lantuejoul S, et al. The inflammatory preatherosclerotic remodeling induced by intermittent hypoxia is attenuated by RANTES/CCL5 inhibition. Am J Respir Crit Care Med. 2011;184(6):724-31. DOI:10.1164/rccm.201012-2033OC.

20. Savransky V, Nanayakkara A, Li J, et al. Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med. 2007;175(12):1290-7. DOI:10.1164/rccm.200612-1771OC.

21. Jun J, Reinke C, Bedja D, et al. Effect of intermittent hypoxia on atherosclerosis in apolipoprotein Edeficient mice. Atherosclerosis. 2010;209(2):381-6. DOI:10.1016/j.atherosclerosis.2009.10.017.

22. Makarenko VV, Usatyuk PV, Yuan G, et al. Intermittent hypoxia-induced endothelial barrier dysfunction requires ROS-dependent MAP kinase activation. Am J Physiol Cell Physiol. 2014;306:C745-52. DOI:10.1152/ajpcell.00313.2013.

23. Dematteis M, Julien C, Guillermet C, et al. Intermittent hypoxia induces early functional cardiovascular remodeling in mice. Am J Respir Crit Care Med. 2008;177:227-35. DOI:10.1164/rccm.200702238OC.

24. Phillips SA, Olson EB, Morgan BJ, et al. Chronic intermittent hypoxia impairs endothelium-dependent dilation in rat cerebral and skeletal muscle resistance arteries. Am J Physiol Heart Circ Physiol. 2004;286:H388-93. DOI:10.1152/ajpheart.00683.2003.

25. Briancon-Marjollet A, Monneret D, Henri M, et al. Endothelin regulates intermittent hypoxia-induced lipolytic remodeling of adipose tissue and phosphorylation of hormone-sensitive lipase. J Physiol. 2016;594:1727-40. DOI:10.1113/JP271321.

26. Gras E, Belaidi E, Briancon-Marjollet A, et al. Endothelin-1 mediates intermittent hypoxia-induced inflammatory vascular remodeling through HIF-1 activation. J Appl Physiol. 2016;120:437-43. DOI:10.1152/japplphysiol.00641.2015.

27. Lefebvre B, Godin-Ribuot D, Joyeux-Faure M, et al. Functional assessment of vascular reactivity after chronic intermittent hypoxia in the rat. Respir Physiol Neurobiol. 2006;150:278-86. DOI:10.1016/j.resp.2005.05.020.

28. Joyeux-Faure M, Stanke-Labesque F, Lefebvre B, et al. Chronic intermittent hypoxia increases infarction in the isolated rat heart. J Appl Physiol. 2005;98:1691-96. DOI:10.1152/japplphysiol.01146.2004.

29. Morand J, Arnaud C, Pepin JL, et al. Chronic intermittent hypoxia promotes myocardial ischemia-related ventricular arrhythmias and sudden cardiac death. Sci Rep. 2018;8(1):2997.DOI:10.1038/s41598-018-21064-y.

30. Campen MJ, Shimoda LA, O'Donnell CP. Acute and chronic cardiovascular effects of intermittent hypoxia in C57BL/6J mice. J Appl Physiol. 2005;99(5):2028-35. DOI:10.1152/japplphysiol.00411.2005.

31. Hayashi T, Yoshioka T, Hasegawa K, et al. Inhalation of hydrogen gas attenuates left ventricular remodeling induced by intermittent hypoxia in mice. Am J Physiol Heart Circ Physiol. 2011;301(3):H1062-9. DOI:10.1152/ajpheart.00150.2011.

32. Li S, Feng J, Wei S, et al. Delayed neutrophil apoptosis mediates intermittent hypoxia-induced progressive heart failure in pressure-overloaded rats. Sleep Breath. 2016;20:95-102. DOI:10.1007/s11325-015-1190-2.

33. Bangash MF, Xie A, Skatrud JB, et al. Cerebrovascular response to arousal from NREM and REM sleep. Sleep. 2008;31:321-7. DOI:10.1093/sleep/31.3.321.

34. Morgan BJ, Crabtree DC, Puleo DS, et al. Neurocirculatory consequences of abrupt change in sleep state in humans. J Appl Physiol. 1996;80:1627-36. DOI:10.1152/jappl.1996.80.5.1627.

35. Brooks D, Horner RL, Kozar LF, et al. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J Clin Invest. 1997;99:106-9. DOI:10.1172/JCI119120.

36. Bao G, Metreveli N, Fletcher EC. Acute and chronic blood pressure response to recurrent acoustic arousal in rats. Am J Hypertens. 1999;12:504-10. DOI:10.1016/s0895-7061(99)00032-1.

37. Launois SH, Averill N, Abraham JH, et al. Cardiovascular responses to nonrespiratory and respiratory arousals in a porcine model. J Appl Physiol. 2001;90:114-20. DOI:10.1152/jappl.2001.90.1.114.

38. Carreras A, Zhang SX, Peris E, et al. Chronic sleep fragmentation induces endothelial dysfunction and structural vascular changes in mice. Sleep. 2014;37:1817-24. DOI:10.5665/sleep.4178.

39. Loredo JS, Ancoli-Israel S, Dimsdale JE. Sleep quality and blood pressure dipping in obstructive sleep apnea. Am J Hypertens. 2001;14:887-92. DOI:10.1016/s0895-7061(01)02143-4.

40. Kasai T, Bradley TD. Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications. J Am Coll Cardiol. 2011;57:119-27. DOI:10.1016/j.jacc.2010.08.627.

41. Parish JM, Somers VK. Obstructive sleep apnea and cardiovascular disease. Mayo Clin Proc. 2004;79:1036-46. DOI:10.4065/79.8.1036.

42. Orban M, Bruce CJ, Pressman GS, et al. Dynamic changes of left ventricular performance and left atrial volume induced by the mueller maneuver in healthy young adults and implications for obstructive sleep apnea, atrial fibrillation, and heart failure. Am J Cardiol. 2008;102:1557-61. DOI:10.1016/j.amjcard.2008.07.050.

43. Linz D, Schotten U, Neuberger HR, et al. Negative tracheal pressure during obstructive respiratory events promotes atrial fibrillation by vagal activation. Heart Rhythm. 2011;8:143643.DOI:10.1016/j.hrthm.2011.03.053.

44. Schlatzer C, Schwarz EI, Sievi NA, et al. Intrathoracic pressure swings induced by simulated obstructive sleep apnoea promote arrhythmias in paroxysmal atrial fibrillation. Europace. 2016;18:64-70. DOI:10.1093/europace/euv122.

45. Linz D, Schotten U, Neuberger HR, et al. Combined blockade of early and late activated atrial potassium currents suppresses atrial fibrillation in a pig model of obstructive apnea. Heart Rhythm. 2011;8:1933-9. DOI:10.1016/j.hrthm.2011.07.018.

46. Monahan K, Brewster J, Wang L, et al. Relation of the severity of obstructive sleep apnea in response to anti-arrhythmic drugs in patients with atrial fibrillation or atrial flutter. Am J Cardiol. 2012;110(3):369-72.DOI:10.1016/j.amjcard.2012.03.037.

47. Fletcher EC, Miller J, Schaaf JW, et al. Urinary catecholamines before and after tracheostomy in patients with obstructive sleep apnea and hypertension. Sleep. 1987;10:35-44. DOI:10.1093/sleep/10.1.35.

48. Dimsdale JE, Coy T, Ziegler MG, et al. The effect of sleep apnea on plasma and urinary catecholamines. Sleep. 1995;18:377-81.

49. Elmasry A, Lindberg E, Hedner J, et al. Obstructive sleep apnoea and urine catecholamines in hypertensive males: a population-based study. Eur Respir J. 2002;19(3):511-7. DOI:10.1183/09031936.02.00106402.

50. Somers VK, Dyken ME, Clary MP, et al. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96(4):1897-904. DOI:10.1172/JCI118235.

51. Carlson JT, Hedner J, Elam M, et al. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest. 1993;103(6):1763-8. DOI:10.1378/chest.103.6.1763.

52. Dick TE, Hsieh YH, Wang N, et al. Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat. Exp Physiol. 2007;92:87-97. DOI:10.1113/expphysiol.2006.035758.

53. Bao G, Metreveli N, Li R, et al. Blood pressure response to chronic episodic hypoxia: role of the sympathetic nervous system. J Appl Physiol. 1997;83:95-101. DOI:10.1152/jappl.1997.83.1.95.

54. Fletcher EC, Lesske J, Culman J, et al. Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. Hypertension. 1992;20:612-619. DOI:10.1161/01.hyp.20.5.612.

55. Nguyen MTA, Favelyukis S, Nguyen AK, et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem. 2007;282:35279-92. DOI:10.1074/jbc.M706762200.

56. Nguyen MTA, Satoh H, Favelyukis S, et al. JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J Biol Chem. 2005;280:361-71. DOI:10.1074/jbc.M504611200.

57. Kim SP, Catalano KJ, Hsu IR, et al. Nocturnal free fatty acids are uniquely elevated in the longitudinal development of diet-induced insulin resistance and hyperinsulinemia. Am J Physiol Endocrinol Metab. 2007;292:E1590-1598. DOI:10.1152/ajpendo.00669.2006.

58. Makino S, Handa H, Suzukawa K, et al. Obstructive sleep apnoea syndrome, plasma adiponectin levels, and insulin resistance. Clin Endocrinol (Oxf). 2006;64:12-19. DOI:10.1111/j.13652265.2005.02407.x.

59. Hedner J, Darpo B, Ejnell H, et al. Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications. Eur Respir J. 1995;8:222-229. DOI:10.1183/09031936.95.08020222.

60. Ziegler MG, Mills PJ, Loredo JS, et al. Effect of continuous positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea. Chest. 2001;120:887-93. DOI:10.1378/chest.120.3.887.

61. Heitmann J, Ehlenz K, Penzel T, et al. Sympathetic activity is reduced by nCPAP in hypertensive obstructive sleep apnoea patients. Eur Respir J. 2004;23:255-262. DOI:10.1183/09031936.04.00015604.

62. Yu L, Li H, Liu X, et al. Left ventricular remodeling and dysfunction in obstructive sleep apnea. Systematic review and meta-analysis. Herz. 2020;45(8):726-38. DOI:10.1007/s00059-01904850-w.

63. Niroumand M, Kuperstein R, Sasson Z, et al. Impact of obstructive sleep apnea on left ventricular mass and diastolic function. Am J Respir Crit Care Med. 2001;163:1632-6. DOI:10.1164/ajrccm.163.7.2007014.

64. Somers VK, Dyken ME, Clary MP, et al. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96:1897-904. DOI:10.1172/JCI118235.

65. Bradley TD, Hall MJ, Ando S, et al. Hemodynamic effects of simulated obstructive apneas in humans with and without heart failure. Chest. 2001;119:1827-35. DOI:10.1378/chest.119.6.1827.

66. Arai M, Alpert NR, MacLennan DH, et al. Alterations in sarcoplasmic reticulum gene expression in human heart failure:a possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. Circ Res. 1993;72:463-9. DOI:10.1161/01.res.72.2.463.

67. Gaasch WH, Blaustein AS, Andrias CW, et al. Myocardial relaxation, II:hemodynamic determinants of rate of left ventricular isovolumic pressure decline. Am J Physiol. 1980;239:H1-H6. DOI:10.1152/ajpheart.1980.239.1.H1

68. Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation. 2000;102:470-9. DOI:10.1161/01.cir.102.4.470.

69. Cloward TV, Walker JM, Farney RJ, et al. Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure. Chest. 2003;124:594-601. DOI:10.1378/chest.124.2.594.

70. Baguet J, Barone-Rochette G, Pépin J. Hypertension and obstructive sleep apnoea syndrome: current perspectives. J Hum Hypertens. 2009;23:431-43. DOI:10.1038/jhh.2008.147.

71. Khan A, Latif F, Hawkins B, et al. Effects of obstructive sleep apnea treatment on left atrial volume and left atrial volume index. Sleep Breath. 2008;12:141-7. DOI 10.1007/s11325-007-0142-x.

72. Hoit BD. Left atrial size and function: role in prognosis J Am Coll Cardiol. 2014;63:493-505. DOI:10.1016/j.jacc.2013.10.055

73. Tsang TSM., Abhayaratna WP, Barnes ME, et al. Prediction of cardiovascular outcomes with left atrial size: is volume superior to area or diameter? J Am Coll Cardiol. 2006;47:1018-23. DOI:10.1016/j.jacc.2005.08.077.

74. Kizer JR, Bella JN, Palmieri V, et al. Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS). Am Heart J. 2006;151:412-8. DOI:10.1016/j.ahj.2005.04.031.

75. Tsang TSM, Barnes ME, Gersh BJ, et al. Prediction of risk for first agerelated cardiovascular events in an elderly population:the incremental value of echocardiography. J Am Coll Cardiol. 2003;42:1199205. DOI:10.1016/s0735-1097(03)00943-4.

76. Todd K, Mcintyre WF, Baranchuk A. Obstructive sleep apnea and atrial fibrillation. Nat Sci Sleep. 2010;2:39-45. DOI:10.2147/NSS.S7625.

77. Gileles-Hillel A, Almendros I, Khalyfa A, et al. Early intermittent hypoxia induces proatherogenic changes in aortic wall macrophages in a murine model of obstructive sleep apnea. Am J Respir Crit Care Med. 2014;190:958-61. DOI:10.1164/rccm.201406-1149LE.

78. Arnaud C, Poulain L, Levy P, et al. Inflammation contributes to the atherogenic role of intermittent hypoxia in apolipoprotein-E knock out mice. Atherosclerosis. 2011;219:425-31. DOI:10.1016/j.atherosclerosis.2011.07.122.

79. Arnaud C, Beguin P, Levy P, et al. Normoxic recovery reverses intermittent hypoxia-induced systemic and vascular inflammation. Chest. 2016;150(2):471-73. DOI:10.1016/j.chest.2016.05.031.

80. 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):9349. DOI:10.1164/ajrccm.165.7.2104126.

81. Sanner BM, Konermann M, Tepel M, et al. Platelet function in patients with obstructive sleep apnoea syndrome. Eur Respir J. 2000;16(4):648-52. DOI:10.1034/j.1399-3003.2000.16d14.x.

82. Lavie L, Dyugovskaya L, Lavie P. Sleep-apnea-related intermittent hypoxia and atherogenesis:adhesion molecules and monocytes/endothelial cells interactions. Atherosclerosis. 2005;183:183-4. DOI:10.1016/j.atherosclerosis.2005.06.024.

83. Dyugovskaya L, Polyakov A, Lavie P, et al. Delayed neutrophil apoptosis in patients with sleep apnea. Am J Respir Crit Care Med. 2008;177:544-54 . DOI:10.1164/rccm.200705-675OC.

84. Htoo AK, Greenberg H, Tongia S, et al. Activation of nuclear factor B in obstructive sleep apnea:a pathway leading to systemic inflammation. Sleep Breath. 2006;10:43-50. DOI:10.1007/s11325005-0046-6.

85. Dyugovskaya L, Lavie P, Hirsh M, et al. Activated CD8+ T lymphocytes in obstructive sleep apnoea. Eur Respir J. 2005;25:820-8. DOI:10.1183/09031936.05.00103204.

86. Dyugovskaya L, Lavie P, Lavie L. Lymphocyte activation as a possible measure of atherosclerotic risk in patients with sleep apnea. Ann NY Acad Sci. 2005;105:340-50. DOI:10.1196/annals.1361.076.

87. 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;168:242-9. DOI:10.1164/rccm.2002101226OC.

88. Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al. Elevated C reactive protein in patients with obstructive sleep apnea. Circulation. 2002;105(21):2462-4. DOI:10.1161/01.cir.0000018948.95175.03.

89. Shamsuzzaman A, Amin RS, Calvin AD, et al. Severity of obstructive sleep apnea is associated with elevated plasma fibrinogen in otherwise healthy patients. Sleep Breath. 2014;18(4):761-6. DOI:10.1007/s11325-014-0938-4.

90. Carreras A, Zhang SX, Almendros I, et al. Resveratrol attenuates intermittent hypoxia-induced macrophage migration to visceral white adipose tissue and insulin resistance in male mice. Endocrinology. 2015;156(2):437-43. DOI:10.1210/en.2014-1706.

91. Poulain L, Thomas A, Rieusset J, et al. Visceral white fat remodeling contributes to intermittent hypoxia-induced atherogenesis. Eur Respir J. 2014;43(2):513-22. DOI:10.1183/09031936.00019913.

92. Murphy AM, Thomas A, Crinion SJ, et al. Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation. Eur Respir J. 2017 19;49(4):1601731. DOI:10.1183/13993003.01731-2016.

93. Drager LF, Bortolotto LA, Figueiredo AC et al. Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling. Chest. 2007;131:1379-86. DOI:10.1378/chest.06-2703.

94. Drager LF, Bortolotto LA, Maki-Nunes C, et al. The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome. Atherosclerosis. 2010;208:490-5. DOI:10.1016/j.atherosclerosis.2009.08.016.

95. Baguet JP, Barone-Rochette G, Tamisier R, et al. Mechanisms of cardiac dysfunction in obstructive sleep apnea. Nat Rev Cardiol. 2012;9:679-88. DOI:10.1038/nrcardio.2012.141.

96. Levy P, Pepin JL, Arnaud C, et al. Intermittent hypoxia and sleep-disordered breathing:current concepts and perspectives. Eur Respir J. 2008;32(4):1082-95. DOI:10.1183/ 09031936.00013308.

97. Levy P, Pépin JL, Arnaud C, et al. Obstructive sleep apnea and atherosclerosis. Prog Cardiovasc Dis. 2009;51:400-10. DOI:10.1016/j.pcad.2009.01.002.

98. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000;279:L1005-28. DOI:10.1152/ajplung.2000.279.6.L1005.

99. Lavie L. Oxidative stress inflammation and endothelial dysfunction in obstructive sleep apnea. Front Biosci. 2012;4:1391-403. DOI:10.2741/469

100. Eltzschig HK, Eckle T. Ischemia and reperfusion-from mechanism to translation. Nat Med. 2011;17(11):1391-401. DOI:10.1038/nm.2507.

101. Stal PS, Johansson B. Abnormal mitochondria organization and oxidative activity in the palate muscles of long-term snorers with obstructive sleep apnea. Respiration. 2012;83(5):407-17. DOI:10.1159/000336040.

102. Wang N, Khan SA, Prabhakar NR, et al. Impairment of pancreatic beta-cell function by chronic intermittent hypoxia. Exp Physiol. 2013;98(9):1376-85. DOI:10.1113/expphysiol.2013.072454.

103. Douglas RM, Ryu J, Kanaan A, et al. Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction. Am J Physiol Cell Physiol. 2010;298(6):C1594-602. DOI:10.1152/ajpcell.00298.2009.

104. Dewan NA, Nieto FJ, Somers, VK. Intermittent hypoxemia and OSA: implications for comorbidities. Chest. 2015;147(1):266-74. DOI:10.1378/chest.14-0500.

105. Gozal D, Khalyfa A, Capdevila OS, et al. Cognitive function in prepubertal children with obstructive sleep apnea:a modifying role for NADPH oxidase p22 subunit gene polymorphisms? Antioxid Redox Signal. 2012;16(2):171-7. DOI:10.1089/ars.2011.4189.

106. Carpagnano GE, Kharitonov SA, Resta O, et al. 8 Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy. Chest. 2003;124(4):1386-92. DOI:10.1378/chest.124.4.1386.

107. Jurado-Gamez B, Fernandez-Marin MC, Gómez-Chaparro JL, et al. Relationship of oxidative stress and endothelial dysfunction in sleep apnoea. Eur Respir J. 2011;37(4):873-9. DOI:10.1183/09031936.00027910.

108. Tan KC, Chow WC, Lam JS, et al. HDL dysfunction in obstructive sleep apnea. Atherosclerosis. 2006;184(2):377-82. DOI:10.1016/j.atherosclerosis.2005.04.024.

109. Vatansever E, Surmen-Gur E, Ursavas A, et al. Obstructive sleep apnea causes oxidative damage to plasma lipids and proteins and decreases adiponectin levels. Sleep Breath. 2011;15(3):275-82. DOI:10.1007/s11325-010-0378-8.

110. Barcelo A, Barbé F, de la Peña M, et al. Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment. Eur Respir J. 2006;27(4):756-60. DOI:10.1183/09031936.06.00067605.

111. Lira AB, de Sousa Rodrigues CF. Evaluation of oxidative stress markers in obstructive sleep apnea syndrome and additional antioxidant therapy: a review article. Sleep Breath. 2016;20(4):115560. DOI:10.1007/s11325-016-1367-3.

112. De Martino T, Ghoul RE, Wang L, et al. Oxidative stress and inflammation differentially elevated in objective versus habitual subjective reduced sleep duration in obstructive sleep apnea. Sleep. 2016;39(7):1361-9. DOI:10.5665/sleep.5964.

113. Bonsignore MR, Borel AL, Machan E, et al. Sleep apnoea and metabolic dysfunction. Eur Respir Rev. 2013;22(129):353-64. DOI:10.1183/09059180.00003413.

114. Kent BD, McNicholas WT, Ryan S. Insulin resistance, glucose intolerance and diabetes mellitus in obstructive sleep apnoea. J Thorac Dis. 2015;7(8):1343-57. DOI:10.3978/j.issn.20721439.2015.08.11.

115. Drager LF, Polotsky VY. Lipid metabolism:a new frontier in sleep apnea research. Am J Respir Crit Care Med. 2011;184(3):288-90. DOI:10.1164/rccm.201105-0837ED.

116. Lévy P, Bonsignore MR, Eckel J. Sleep, sleep-disordered breathing and metabolic consequences. Eur Respir J. 2009;34(1):243-60. DOI:10.1183/09031936.00166808.

117. Iiyori N, Alonso LC, Li J, et al. Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. Am J Respir Crit Care Med. 2007;175(8):851-7. DOI:10.1164/rccm.200610-1527OC.

118. Xu J, Long YS, Gozal D, еt al. Beta-cell death and proliferation after intermittent hypoxia:role of oxidative stress. Free Radic Biol Med. 2009;46(6):783-90. DOI:10.1016/j.freeradbiomed.2008.11.026.

119. Spiegel K, Tasali E, Penev P, et al. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004;141(11):846-50. DOI:10.7326/0003-4819-141-11-20041207000008.

120. Gozal D, Khalyfa A, Qiao Z, et al. Protein-Tyrosine Phosphatase-1B mediates sleep fragmentationinduced insulin resistance and visceral adipose tissue inflammation in mice. Sleep. 2017;40(9):28. DOI:10.1093/sleep/zsx111.

For citation:

Agaltsov M.V., Drapkina O.M. Obstructive sleep apnea and cardiovascular comorbidity: common pathophysiological mechanisms to cardiovascular disease. Rational Pharmacotherapy in Cardiology. 2021;17(4):594-605. (In Russ.)

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