Nejat ALTINTAŞ, Pınar ACAR, Muzaffer SARIAYDIN, Nurşen YAŞAYANCAN

The right heart diaries in sleep disordered breathing

Epidemiyolojik çalışmalar, uyku apnenin, bireylerin demografik özelliklerinden ve risk markörlerinden yani sigara, alkol, obesite, diabet, dislipidemi, atrial fibrilayon ve hipertansiyondan bağımsız olarak kardiovasküler riski artırdığını gösterir. Ciddi uyku apneli bireyler artmış pulmoner arteriyel hipertansiyon riski altındadır. Tıkayıcı uyku apne ile pulmoner hipertansiyon ilişkisi altında yatan mekanizma tam anlamıyla tanımlanmamıştır. Uzamış sempatik aktivasyon, intratorasik basınç değişiklikleri ve oksidatif stress gibi bazı ara mekanizmalar katılabilir. Koagülasyon faktörü, endotel hasarı, trombosit aktivasyonu ve artmış inflamasyon mediatörleri ile ilgili hastaliklar gibi diğer anomalilerde pulmoner hipertansiyon ve kardiovasküler hastalıkların patogenezinde rol oynayabilir. Tıkayıcı uyku apneli hastaların pozitif yüksek hava yolu basıncı ile tedavisi sonucunda sistolik kan basıncında düşmesi, sol venrikül sistolik fonksiyonunda düzelmesi ve trombsosit aktivasyonunda azalmasi gibi kanıtlar, tıkayıcı uyku apne ile pulmoner hipertansiyon arasında ilişki olduğunu destekler. Pulmoner hipertansiyon ile uyku apne sendromu arasındaki kompleks ilişkinin gösterilmesi için daha fazla sistematik çalışmaya ihtiyaç vardır.

Uykudaki solunum bozukluğunda, sağ kalp günlükleri

Epidemiologic studies show that sleep apnea increases risks for cardiovascular disease independently of individuals’ demographic characteristics or risk markers i.e., smoking, alcohol, obesity, diabetes, dyslipidemia, atrial fibrillation, and hypertension. Individuals with severe sleep apnea are at increased risk for pulmonary arterial hypertension. The underlying mechanisms explaining associations between obstructive sleep apnea and pulmonary arterial hypertension are not entirely delineated. Several intermediary mechanisms might be involved including sustained sympathetic activation, intrathoracic pressure changes, and oxidative stress. Other abnormalities such as disorders in coagulation factors, endothelial damage, platelet activation, and increased inflammatory mediators might also play a role in the pathogenesis of pulmonary hypertension and cardiovascular disease. Linkage between obstructive sleep apnea and pulmonary arterial hypertension is corroborated by evidence that treatment of sleep apnea with continuous positive airway pressure reduces systolic blood pressure, improves left ventricular systolic function, and diminishes platelet activation. Several systematic studies are necessary to explicate complex associations between sleep apnea and pulmonary hypertension.

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1. Young T, Palte M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328:1230-1235
2. Rafanan AL, Golish JA, Dinner DS. Nocturnal hypoxemia is common in primary pulmonary hypertension.Chest 2001; 120:894-899
3. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995:1897-1904
4. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 305:1046–1053
5. Motley HL, Cournand A, Werko L, Himmelstein A, Dresdale D. The influence of short periods of induced acute anoxia upon pulmonary artery pressures in man. Am J Physiol 1947;150:315–320
6. Barst RJ, McGoon M, Torbicki A, et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43:40S–47S
7. Marrone O, Bonsignore MR. Pulmonary haemodynamics in obstructive sleep apnoea. Sleep Med Rev 2002; 6
8. Krishnan V, Hassaun P, Hummers L, Collop NA. Sleep disordered breathing and pulmonary hypertension. Sleep. 2005;20:A300.
9. Simonneau G, Galiè N,Rubin LJ, et al. Clinical classification of pulmonary hypertension. Am Coll Cardiol 2004 Jun 16;43:5-12
10. Veerman DP, İmholz BP, Wieling W, Wesseling KH, van Montfrans GA. Circadian profile of systemic hemodynamics. Hypertension 1995;26:55-9.
11. Rowlands DB ST, Watson RDS, Littler WA. The influence of physical activity on arterial pressure during ambulatory recordings in man. Clin Sci 1980; 58:115-117
12. Mann S, Craig MW, Melville DI, Balasubramanian V, Raftery EB. Physical activity and the circadian rhythm of blood pressure. Clin Sci 1979; 57:291-294
13. Somers VK Dyken ME, Mark AL, Abboud FM. Sympatheticnerve activity during sleep in normal subjects. N Engl J Med 1993; 328:303-307
14. Mancia G. Autonomic modulation of the cardiovascular system during sleep. N Eng J Med 1993; 328
15. Bakshi MS, Hoskere G, Mehta JB, Chidambaram B, Ponder M, Girish MR. Circulatory response in sleep apnea patients during sleep before and after CPAP treatment. Sleep. 2005;20:A194
16. Bonsignore MR, Marrone O, Insalaco G, Bonsignore G. The cardiovascular effects of obstructive sleep apnoeas: analysis of pathogenic mechanisms. Eur Respir J 1994; 7:786-805
17. Marrone O, Bellia V, Ferrara G, et al. Transmural pressure measurements. İmportance in the assessment of pulmonary hypertension in obstructive sleep apneas. Chest 1989; 95:338-342
18. Marrone O, Romano S. Pulmonary artery pressure in obstructive apneas: influence of intrathoracic pressure and hypoxia. Am Rev Respir Dis 1993; 147:1017
19. Phillips BG, Narkiewicz K, Pesek CA, Haynes WG, Dyken ME, SomersVK. Effects of obstructive sleep apnea on endothelin- 1 and blood pressure. J Hypertens. 1999;17:61– 66.
20. Carpagnano GE, Spanevello A, Sabato R, et al. Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome. Transl Res. 2008 Jan;151(1):45-50.
21. Ahmed Q, Chung-Park M, Tomashefski J. Cardiopulmonary pathology in patients with sleep apnea/obesity hypoventilation syndrome. Hum Pathol 1997;28:264–269
22. 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 Feb;149:416-22.
23. Sajkov D, Wang T, Saunders NA, Bune AJ, Neill AM, Douglas MR. Daytime pulmonary hemodynamics in patients with obstructive sleep apnea without lung disease. Am J Respir Crit Care Med. 1999 ;159:1518-26.
24. Dikmenoğlu N, Ciftçi B, İleri E, et al. Erythrocyte deformability, plasma viscosity and oxidative status in patients with severe obstructive sleep apnea syndrome. Sleep Med. 2006 Apr;7:255-61
25. Reinhart WH, Oswald J, Walter R, Kuhn M. Blood viscosity and platelet function in patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure. Clin Hemorheol Microcirc. 2002;27:201-7.
26. Podszus T, Mayer J, Penzel T, et al. Nocturnalhemodynamics in patients with sleep apnea. Eur J Respir Dis 1986;146:435–42.
27. Hawrylkiewicz I, Palasiewicz G, Plywaczewski R,et al. Pulmonary hypertension in patients with pure obstructive sleep apnea]. Pol Arch Med Wewn 2004;111:449–54
28. Chaouat A, Weitzenblum E, Krieger J, et al. Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients.Chest 1996;109:380–6.
29. Bradley TD, Rutherford R, Grossman RF, et al. Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome. Am Rev Respir Dis 1985;131:835–9.
30. Weitzenblum E, Krieger J, Apprill M, et al. Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome. Am Rev Respir Dis 1988;138:345–9.
31. Chaouat A, Weitzenblum E, Krieger J, et al. Association of chronic obstructive pulmonary disease and sleep apnea syndrome. Am J Respir Crit Care Med 1995;151:82–6.
32. Dursunoglu N, Dursunoglu D, Kilic M. Impact of obstructive sleep apnea on right ventricular global function: sleep apnea and myocardial performance index. Respiration 2005;72:278–84.
33. Sanner BM, Konermann M, Sturm A, et al. Right ventricular dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J 1997;10:2079–83.
34. Dursunoglu D, Dursunoglu N, Evrengul H, et al.Impact of obstructive sleep apnoea on left ventricular mass and global function. Eur Respir J 2005;26:283–8.
35. Romero-Corral A, Somers VK, Pellikka PA, et al.Decreased right and left ventricular myocardialperformance in obstructive sleep apnea. Chest2007;132:1863–70.
36. Otto ME, Belohlavek M, Romero-Corral A, et al.Comparison of cardiac structural and functional changes in obese otherwise healthy adults with versus without obstructive sleep apnea. Am J Cardiol 2007;99:1298–302.
37. Gami AS, Hodge DO, Herges RM, et al. Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J Am Coll Cardiol 2007;49:565–71.
38. Levy D, Garrison RJ, Savage DD, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990;322:1561–6.
39. Guidry UC, Mendes LA, Evans JC, et al. Echocardiographic features of the right heart in sleep-disorderedbreathing: the Framingham Heart Study. Am J Respir Crit Care Med 2001;164:933–8.
40. Marrone O Bollero V, Ferrara G, et al. Transmural pressure measurements. İmportance in the assessment of pulmonary hypertension in obstructive sleep apneas. Chest 1989; 95:338-342
41. Sajkov D CR, Thornton AT, Espinoza HA, McEvoy RD. Pulmonary hypertension and hypoxemia in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 1994; 149:416-422
42. Marrone O, Bollero V, Pieri D, Salvaggio A, Bonsignore, G. M. Acute effects of oxygen administration on transmural pulmonary artery pressure in obstructive sleep apnea. Chest 1992; 101:1023-1027
43. Emery C SP, Mohammed F, Barer G. The action of hypercapnia during hypoxia on pulmonary vessels. Bull Eur Physiopathol Respir 1977;
44. Shivalkar B, Van De Heyning C, Kerremans M, Rinkevich D, Verbraecken J, De Backer W, et al. Obstructive Sleep Apnea Syndrome. Journal of the Am Coll Cardiol 2006;47(7):1433–9.
45. Robotham J LW, Holland L, MacGregor D, Bryan, A RJ. Effects of respiration on cardiac performance. J Appl Physiol: Respirat Environ Exercise Physiol 1978; 44:703- 709
46. Scharf SM. Cardiovascular effects of airways obstruction. Lung 1991; 169:1-23
47. Bradley TD. Right and left ventricular function impairment and sleep apnea. Clin Chest Med 1992; 13:459-479
48. Chaudary B, Ferguson D, Speir W. Pulmonary edema as a presenting feature of sleep apnea syndrome. Chest 1982; 82:122-124
49. Iwase N, Kikuchi Y, Hida W, et al. Effects of repetitive air way obstruction on O2 saturation and systemic and pulmonary arterial pressure in anesthetized dogs. Am Rev Respir Dis 1992; 146:1402-1410
50. Garpestad E Katayama H, Parker J, et al. Stroke volume and cardiac output decrease at termination of obstructive apneas. J Appl Physiol 1992;73:1743-1748
51. Iwase N Kikuchi Y, Hida W, et al. Effects of phentolamine and carotid body resection on pulmonary artery and systemic artery pressure during repetitive airway obstruction. Am Rev Respir Dis 1989; 39:A181
52. Naeije R, Lejeune P, Leeman M, Melot C, Closset J. Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs. J Appl Physiol Rev 1989; 66:42-50
53. Prabhakar NR, Peng YJ, Jacono FJ, Kumar GK, Dick TE. Cardiovascular alterations by chronic intermittent hypoxia: importance of carotid body chemoreflexes. Clin Exp Pharmacol Physiol. 2005;32:447-449.
54. Allahdadi KJ, Walker BR, Kanagy NL. Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension. Hypertension. 2005;45:705-709.
55. Rodway GW, Sethi JM, Hoffman LA, et al. İntermittent hypoxia (İH) versus continuous hypoxia (CH): impact on hemodynamic variables and iNOS expression. Sleep. 2005;20:A211
56. Yamauchi M, Nakano H, Maekawa J, et al. Oxidative stress in obstructive sleep apnea. Chest. 2005;127:1674-1679.
57. Teramoto S, Yamamoto H, Yamaguchi Y, Namba R, Ouchi Y. Obstructive sleep apnea causes systemic inflammation and metabolic syndrome. Chest. 2005;127:1074-1075.
58. Kataoka T, Enomoto F, Kim R, et al. The effect of surgical treatment of obstructive sleep apnea syndrome on the plasma TNF-alpha levels. Tohoku J Exp Med. 2004;204:267-272.
59. Hawrylkiewicz I, Sliwinski P, Gorecka D, Plywaczewski R, Zielinski J. Pulmonary haemodynamics in patients with OSAS or an overlap syndrome. Monaldi Arch Chest Dis. 2004;61:148-52.
60. Hung TH, Charnock-Jones DS, Skepper JN, Burton GJ. Secretion of tumor necrosis factor-alpha from human placental tissues induced by hypoxia-reoxygenation causes endothelial cell activation in vitro: a potential mediator of the inflammatory response in preeclampsia. Am J Pathol. 2004;164:1049-1061.. Monaldi Arch Chest Dis. 2004;61:148-152.
61. Sharafkhaneh H, Hirshkowitz M, Sharafkhaneh A, Bozkurt B. Endothelial dependent vascular dilation is abnormal in patients with obstructive sleep apnea. Sleep. 2005;20:A210.
62. Lopez-Ramos JC, Martinez-Romero R, Molina F, et al. Evidence of a decrease in nitric oxide-storage molecules following acute hypoxia and/or hypobaria, by means of chemiluminescence analysis. Nitric Oxide. 2005 ;13:62-7.
63. Naughton MT. .The link between obstructive sleep apnea and heart failure: underappreciated opportunity for treatment. Curr Cardiol Rep. 2005;7:211-215.
64. Poyares D, Guilleminault C. Sleep and endothelium activation in patients with UARS and severe OSA, preliminary report. Sleep. 2005;20:A196
65. Parish J, Shepard J. Cardiovascular effects of sleep disorders. Chest. 1990;97(5):1220–6.
66. Morgenthaler T, Lerman A. Endothelial dysfunction assessed by peripheral arterial tonometry in obstructive sleep apnea patients improves with CPAP therapy. Sleep. 2005;20(suppl):A177.
67. Alchanatis M, Tourkohoriti G, Kakouros S, Kosmas E, Podaras S. Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics. Respiration 2001; 68:566-572
68. 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; 165:152-158
69. 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; 27:1106-1113
70. Fletcher EC, Schaaf JW, Miller J, et al. Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease. Am Rev Respir Dis 1987;135:525–33.
71. Krieger J, Sforza E, Apprill M, et al. Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients. Chest 1989;96:729–37.
72. Shinozaki T, Tatsumi K, Sakuma T, et al. Daytime pulmonary hypertension in the obstructive sleep apnea syndrome. Nihon Kyobu Shikkan GakkaiZasshi 1995;33:1073–9
73. Laks L, Lehrhaft B, Grunstein RR, et al. Pulmonary hypertension in obstructive sleep apnoea. Eur Respir J 1995;8:537–41.
74. Bady E, Achkar A, Pascal S, et al. Pulmonary arterial hypertension in patients with sleep apnoea syndrome. Thorax 2000;55:934–9.