Pulmonary hypertension in obstructive sleep apnea: Is it clinically significant? a critical analysis of the association and pathophysiology

Pulmonary Circulation

Volumn 5, Issue 2, 2015, Pages 220-227

  Kholdani, Cyrus ^a   Fares, Wassim H ^a   Mohsenin, Vahid ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Heart failure; Hypoxic vasoconstriction; Obstructive sleep apnea; Pulmonary hypertension

Indexed keywords

EID: 85026336846     PISSN: 20458932     EISSN: 20458940     Source Type: Journal    
DOI: 10.1086/679995     Document Type: Review

References (86)

1. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013;62:D34-D41.
2. Oudiz RJ. Pulmonary hypertension associated with left-sided heart disease. Clin Chest Med 2007;28:233-241.
3. Strange G, Playford D, Stewart S, Deague JA, Nelson H, Kent A, et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart 2012;98:1805-1811.
4. Hansdottir S, Groskreutz DJ, Gehlbach BK. WHOs in second?: a practical review of World Health Organization group 2 pulmonary hypertension. Chest 2013;144:638-650.
5. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc 2008;5:136-143.
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;342:1378-1384.
7. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005;353:2034-2041.
8. Shah NA, Yaggi HK, Concato J, Mohsenin V. Obstructive sleep apnea as a risk factor for coronary events or cardiovascular death. Sleep Breath 2009;14:131-136.
9. 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;173:910-916.
10. 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;34:1744-1749.
11. Gami AS, Olson EJ, Shen WK, Wright RS, Ballman KV, Hodge DO, et al. Obstructive sleep apnea and the risk of sudden cardiac death: a longitudinal study of 10,701 adults. J Am Coll Cardiol 2013;62:610-616.
12. 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;109:380-386.
13. Bady E, Achkar A, Pascal S, Orvoen-Frija E, Laaban JP. Pulmonary arterial hypertension in patients with sleep apnoea syndrome. Thorax 2000;55:934-939.
14. Alchanatis M, Tourkohoriti G, Kakouros S, Kosmas E, Podaras S, Jordanoglou JB. Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics. Respiration 2001;68:566-572.
15. Sajkov D, McEvoy RD. Obstructive sleep apnea and pulmonary hypertension. Prog Cardiovasc Dis 2009;51:363-370.
16. Sajkov D, Wang T, Saunders NA, Bune AJ, Neill AM, Douglas Mcevoy R. Daytime pulmonary hemodynamics in patients with obstructive sleep apnea without lung disease. Am J Respir Crit Care Med 1999;159:1518-1526.
17. Hetzel M, Kochs M, Marx N, Woehrle H, Mobarak I, Hombach V, et al. Pulmonary hemodynamics in obstructive sleep apnea: frequency and causes of pulmonary hypertension. Lung 2003;181:157-166.
18. Ulrich S, Fischler M, Speich R, Bloch KE. Sleep-related breathing disorders in patients with pulmonary hypertension. Chest 2008;133:1375-1380.
19. Jilwan FN, Escourrou P, Garcia G, Jaïs X, HumbertM, Roisman G. High occurrence of hypoxemic sleep respiratory disorders in precapillary pulmonary hypertension and mechanisms. Chest 2013;143:47-55.
20. Dumitrascu R, Tiede H, Eckermann J, Mayer K, Reichenberger F, Ghofrani HA, et al. Sleep apnea in precapillary pulmonary hypertension. Sleep Med 2013;14:247-251.
21. Kauppert CA, Dvorak I, Kollert F, Heinemann F, Jorres RA, Pfeifer M, et al. Pulmonary hypertension in obesity-hypoventilation syndrome. Respir Med 2013;107:2061-2070.
22. Minai OA, Ricaurte B, Kaw R, Hammel J, Mansour M, McCarthy K, et al. Frequency and impact of pulmonary hypertension in patients with obstructive sleep apnea syndrome. Am J Cardiol 2009;104:1300-1306.
23. Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology 1993;78:427-435.
24. Bartsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 1991;325:1284-1289.
25. Enson Y, Giuntini C, Lewis ML, Morris TQ, Ferrer MI, Harvey RM. The influence of hydrogen ion concentration and hypoxia on the pulmonary circulation. J Clin Invest 1964;43:1146-1162.
26. Bergofsky EH, Haas F, Porcelli R. Determination of the sensitive vascular sites from which hypoxia and hypercapnia elicit rises in pulmonary arterial pressure. Fed Proc 1968;27:1420-1425.
27. Arborelius M Jr, Lundin G, Svanberg L, Defares JG. Influence of unilateral hypoxia on blood flow through the lungs in man in lateral position. J Appl Physiol 1960;15:595-597.
28. Defares JG, Lundin G, Arborelius M Jr, Stromblad R, Svanberg L. Effect of unilateral hypoxia on pulmonary blood flow distribution in normal subjects. J Appl Physiol 1960;15:169-174.
29. Preston IR. Clinical perspective of hypoxia-mediated pulmonary hypertension. Antioxid Redox Signal 2007;9:711-721.
30. Wu W, Platoshyn O, Firth AL, Yuan JX. Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2007;293: 952-959.
31. Demiryurek AT, Wadsworth RM, Kane KA, Peacock AJ. The role of endothelium in hypoxic constriction of human pulmonary artery rings. Am Rev Respir Dis 1993;147:283-290.
32. Takemoto M, Sun J, Hiroki J, Shimokawa H, Liao JK. Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation 2002;106:57-62.
33. Beleslin-Cokic BB, Cokic VP, Wang L, Piknova B, Teng R, Schechter AN, et al. Erythropoietin and hypoxia increase erythropoietin receptor and nitric oxide levels in lung microvascular endothelial cells. Cytokine 2011;54:129-135.
34. Krotova K, Patel JM, Block ER, Zharikov S. Hypoxic upregulation of arginase II in human lung endothelial cells. Am J Physiol Cell Physiol 2010;299:C1541-C1548.
35. Yu L, Quinn DA, Garg HG, Hales CA. Heparin inhibits pulmonary artery smooth muscle cell proliferation through guanine nucleotide exchange factor-H1/RhoA/Rho kinase/p27. Am J Resp Cell Mol Biol 2011;44:524-530.
36. Penaloza D, Sime F, Banchero N. Pulmonary hypertension in healthy man born and living at high altitude: Fifth Aspen Lung Conference: normal and abnormal pulmonary circulation. Med Thoracic 1962;19: 449-460.
37. Arias-Stella J, Recavarren S. Right ventricular hypertrophy in native children living at high altitude. Am J Pathol 1962;41:55-64.
38. Kessler R, Chaouat A, Schinkewitch P, Faller M, Casel S, Krieger J, et al. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest 2001;120:369-376.
39. Boysen PG, Block AJ, Wynne JW, Hunt LA, Flick MR. Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease. Chest 1979;76:536-542.
40. Hedner J, Ejnell H, Caidahl K. Left ventricular hypertrophy independent of hypertension in patients with obstructive sleep apnoea. J Hypertens 1990;8:941-946.
41. Bitter T, Faber L, Hering D, Langer C, Horstkotte D, Oldenburg O. Sleep-disordered breathing in heart failure with normal left ventricular ejection fraction. Eur J Heart Fail 2009;11:602-608.
42. Chami HA, Devereux RB, Gottdiener JS, Mehra R, Roman MJ, Benjamin EJ, et al. Left ventricular morphology and systolic function in sleep-disordered breathing: the Sleep Heart Health study. Circulation 2008;117:2599-2607.
43. Gottlieb DJ, Yenokyan G, Newman AB, OConnor GT, Punjabi NM, Quan SF, et al. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the Sleep Heart Health study. Circulation 2010;122:352-360.
44. Segers VF, Brutsaert DL, De Keulenaer GW. Pulmonary hypertension and right heart failure in heart failure with preserved left ventricular ejection fraction: pathophysiology and natural history. Curr Opin Cardiol 2012;27:273-280.
45. Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM. Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Cardiol 2009;53:1119-1126.
46. Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001;37:183-188.
47. Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 2003; 348:500-509.
48. Voelkel NF, Mizuno S, Bogaard HJ. The role of hypoxia in pulmonary vascular diseases: a perspective. Am J Physiol Lung Cell Mol Physiol 2013;304:L457-L465.
49. McGuire M, Bradford A. Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats. Eur Respir J 2001;18:279-285.
50. Campen MJ, Shimoda LA, ODonnell CP. Acute and chronic cardiovascular effects of intermittent hypoxia in C57BL/6J mice. J Appl Physiol (1985) 2005;99:2028-2035.
51. Sheikh AQ, Lighthouse JK, Greif DM. Recapitulation of developing artery muscularization in pulmonary hypertension. Cell Rep 2014;6: 809-817.
52. Nisbet RE, Graves AS, Kleinhenz DJ, Rupnow HL, Reed AL, Fan TH, et al. The role of NADPH oxidase in chronic intermittent hypoxiainduced pulmonary hypertension in mice. Am J Resp Cell Mol Biol 2009;40:601-609.
53. Li JM, Shah AM. Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. Am J Physiol Regul Integr Comp Physiol 2004;287:1014-1030.
54. Egermayer P, Town GI, Peacock AJ. Role of serotonin in the pathogenesis of acute and chronic pulmonary hypertension. Thorax 1999;54: 161-168.
55. MacLean MR, Herve P, Eddahibi S, Adnot S. 5-hydroxytryptamine and the pulmonary circulation: receptors, transporters and relevance to pulmonary arterial hypertension. Br J Pharmacol 2000;131:161-168.
56. Launay JM, Herve P, Peoch K, Tournois C, Callebert J, Nebigil CG, et al. Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat Med 2002;8:1129-1135.
57. Augustin HG, Koh GY, Thurston G, Alitalo K. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 2009;10:165-177.
58. Pichiule P, Chavez JC, LaManna JC. Hypoxic regulation of angiopoietin- 2 expression in endothelial cells. J Biol Chem 2004;279:12171-12180.
59. Zhao YD, Campbell AI, Robb M, Ng D, Stewart DJ. Protective role of angiopoietin-1 in experimental pulmonary hypertension. Circ Res 2003; 92:984-991.
60. Kugathasan L, Ray JB, Deng Y, Rezaei E, Dumont DJ, Stewart DJ. The angiopietin-1-Tie2 pathway prevents rather than promotes pulmonary arterial hypertension in transgenic mice. J Exp Med 2009;206:2221-2234.
61. Karapinar H, Esen O, Emiroglu Y, Akcakoyun M, Pala S, Kargin R, et al. Serum levels of angiopoietin-1 in patients with pulmonary hypertension due to mitral stenosis. Heart Vessels 2011;26:536-541.
62. Wang Z, Li AY, Guo QH, Zhang JP, An Q, Guo YJ, et al. Effects of cyclic intermittent hypoxia on ET-1 responsiveness and endothelial dysfunction of pulmonary arteries in rats. PLoS One 2013;8:58078.
63. Cody RJ, Haas GJ, Binkley PF, Capers Q, Kelley R. Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. Circulation 1992;85:504-509.
64. Yoshibayashi M, Nishioka K, Nakao K, Saito Y, Matsumura M, Ueda T, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects: evidence for increased production of endothelin in pulmonary circulation. Circulation 1991;84:2280-2285.
65. Ooi H, Colucci WS, Givertz MM. Endothelin mediates increased pulmonary vascular tone in patients with heart failure: demonstration by direct intrapulmonary infusion of sitaxsentan. Circulation 2002;106: 1618-1621.
66. Packer M, McMurray J, Massie BM, Caspi A, Charlon V, Cohen-Solal A, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. J Card Fail 2005;11:12-20.
67. Kaluski E, Cotter G, Leitman M, Milo-Cotter O, Krakover R, Kobrin I, et al. Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension-a multicenter randomized study. Cardiology 2008;109:273-280.
68. Moller DS, Lind P, Strunge B, Pedersen EB. Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea. Am J Hypertens 2003;16:274-280.
69. Mohsenin V, Urbano F. Circulating antiangiogenic proteins in obstructive sleep apnea and hypertension. Respir Med 2011;105:801-807.
70. Wang B, Yan B, Song D, Ye X, Liu SF. Chronic intermittent hypoxia down-regulates endothelial nitric oxide synthase expression by an NF- κB-dependent mechanism. Sleep Med 2012;14:165-171.
71. Foresi A, Leone C, Olivieri D, Cremona G. Alveolar-derived exhaled nitric oxide is reduced in obstructive sleep apnea syndrome. Chest 2007;132:860-867.
72. Jafari B, Mohsenin V. Activation of heme oxygenase and suppression of cGMP are associated with impaired endothelial function in obstructive sleep apnea with hypertension. Am J Hypertens 2012;25:854-861.
73. Schwappacher R, Kilic A, Kojonazarov B, Lang M, Diep T, Zhuang S, et al. A molecular mechanism for therapeutic effects of cGMP-elevating agents in pulmonary arterial hypertension. J Biol Chem 2013;288: 16557-16566.
74. Ghofrani HA, Galiè N, Grimminger F, Grünig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013;369:330-340.
75. Burger CD, Foreman AJ, Miller DP, Safford RE, McGoon MD, Badesch DB. Comparison of body habitus in patients with pulmonary arterial hypertension enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management with normative values from the National Health and Nutrition Examination Survey. Mayo Clin Proc 2011;86: 105-112.
76. Hansmann G, Rabinovitch M. The protective role of adiponectin in pulmonary vascular disease. Am J Physiol Lung Cell Mol Physiol 2009; 298:L1-L2.
77. Vatansever E, Surmen-Gur E, Ursavas A, Karadag M. Obstructive sleep apnea causes oxidative damage to plasma lipids and proteins and decreases adiponectin levels. Sleep Breath 2010;15:275-282.
78. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. 1999. Biochem Biophys Res Commun 2012;425:560-564.
79. Medoff BD, Okamoto Y, Leyton P, Weng M, Sandall BP, Raher MJ, et al. Adiponectin deficiency increases allergic airway inflammation and pulmonary vascular remodeling. Am J Resp Cell Mol Biol 2009; 41:397-406.
80. Summer R, Fiack CA, Ikeda Y, Sato K, Dwyer D, Ouchi N, et al. Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease. Am J Physiol Lung Cell Mol Physiol 2009;297:L432-L438.
81. Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiéry JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009;30:2493-2537.
82. Janda S, Shahidi N, Gin K, Swiston J. Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and metaanalysis. Heart 2011;97:612-622.
83. Sforza E, Krieger J, Weitzenblum E, Apprill M, Lampert E, Ratamaharo J. Long-term effects of treatment with nasal continuous positive airway pressure on daytime lung function and pulmonary hemodynamics in patients with obstructive sleep apnea. Am Rev Resp Dis 1990;141:866-870.
84. 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.
85. 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.
86. Nahmias J, Lao R, Karetzky M. Right ventricular dysfunction in obstructive sleep apnoea: reversal with nasal continuous positive airway pressure. Eur Respir J 1996;9:945-951.