Mechanismen der kardiovaskulären Komorbidität bei Patienten mit obstruktivem Schlafapnoesyndrom

Zusammenfassung

Die bei obstruktiver Schlafapnoe repetitiv auftretende intermittierende Hypoxie, zentralnervöse Weckreaktion und intrathorakale Druckschwankung sind als wesentliche pathophysiologische Mechanismen für die kardiovaskuläre Komorbidität verantwortlich. Diese Phänomene führen zu vermehrtem oxidativen Stress, systemischer Inflammation, Störungen der Vasomotorik, Steigerung sympathischer Aktivität und Arteriosklerose der Blutgefäße. Die CPAP-Therapie senkt den arteriellen Blutdruck und hat einen positiven Effekt auf wesentliche Einzelaspekte der kardiovaskulären Komorbidität. Vor der Veröffentlichung bereits laufender randomisierter Studien werden wir im klinischen Alltag im Einzelfall entscheiden müssen, ob allein die kardiovaskuläre Situation eine CPAP-Therapie rechtfertigt. Dies wird insbesondere dann der Fall sein, wenn eine schwere OSA vorliegt, eine Tagesmüdigkeit besteht, eine gute Compliance gegeben ist und die Patienten jünger sind. Auf jeden Fall sinnvoll sind Maßnahmen, die das kardiovaskuläre Risiko senken und dabei gleichzeitig einen positiven Einfluss auf die OSA haben, d. h. Gewichtsreduktion, körperliches Training und Tabakentwöhnung.

Abstract

The repetitive intermittent hypoxic episodes, central nervous arousal and intrathoracic pressure fluctuations that occur together with obstructive sleep apnoea are the primary pathophysiological mechanisms responsible for the cardiovascular co-morbidity. These phenomena lead to increased oxidative stress, systemic inflammation, disrupted vasomotor function, increased sympathetic activity and the development of arteriosclerosis in blood vessels. CPAP therapy lowers arterial blood pressure and has a positive effect on relevant specific aspects of cardiovascular co-morbidity. Until the results of current randomised studies have been published, it has to be decided on an individual basis whether the cardiovascular situation alone justifies CPAP therapy. This will usually be the case in severe OSA with daytime sleepiness, in young patients and patients with good compliance. Interventions that reduce cardiovascular risk and also have a positive effect on OSA, i. e., weight reduction, physical exercise and smoking cessation are always appropriate.

• Literatur

• 1 Bradley TD, Brown IG, Grossman RF et al. Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea. N Engl J Med 1986; 315: 1327-1331
• 2 Peppard PE, Young T, Palta M et al. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA 2000; 284: 3015-3021
• 3 Young T, Palta M, Dempsey J et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328: 1230-1235
• 4 Duran J, Esnaola S, Rubio R et al. Obstructive sleep apnea-hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med 2001; 163: 685-689
• 5 Owan TE, Hodge DO, Herges RM et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355: 251-259
• 6 Lüthje L, Andreas S. Obstructive sleep apnea and coronary artery disease. Sleep Medicine Review 2008; 12: 19-31
• 7 Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009; 373: 82-93
• 8 Hung J, Whitford EG, Parsons RW et al. Association of sleep apnoea with myocardial infarction in men. Lancet 1990; 336: 261-264
• 9 Buchner S, Greimel T, Hetzenecker A et al. Natural course of sleep-disordered breathing after acute myocardial infarction. Eur Respir J 2012; epub ahead of print
• 10 Schulz R, Blau A, Borgel J et al. Sleep apnoea in heart failure - results of a German survey. Eur Respir J 2007; 29: 1201-1205
• 11 Bradley TD, Floras JS. Sleep apnea and heart failure: Part II: central sleep apnea. Circulation 2003; 107: 1822-1826
• 12 Morgan BJ, Denahan T, Ebert TJ. Neurocirculatory consequences of negative intrathoracic pressure vs. asphyxia during voluntary apnea. J Appl Physiol 1993; 74: 2969-2975
• 13 Andreas S, Bingeli C, Mohacsi P et al. Nasal oxygen and muscle sympathetic nerve activity in heart failure. Chest 2003; 123: 366-371
• 14 Davies RJ, Belt PJ, Roberts SJ et al. Arterial blood pressure responses to graded transient arousal from sleep in normal humans. J Appl Physiol 1993; 74: 1123-1130
• 15 Andreas S, Werner GS, Sold G et al. Doppler echocardiographic analysis of cardiac flow during the Mueller manoeuver. Eur J Clin Invest 1991; 21: 72-76
• 16 Scharf SM. Cardiovascular effects of airways obstruction. Lung 1991; 169: 1-23
• 17 Andreas S, Richter DW. Changes in heart rate during obstructive sleep apnea. Eur Respir J 1993; 6: 1074
• 18 Bonsignore MR, Romano S, Marrone O et al. Different heart rate patterns in obstructive apneas during NREM sleep. Sleep 1997; 20: 1167-1174
• 19 Andreas S, Hajak G, Natt P et al. ST segmental changes and arrhythmias in obstructive sleep apnea. Pneumol 1991; 45: 720-724
• 20 Andreas S, von Breska B, Schaumann A et al. Obstructive sleep apnoea and signal averaged electrocardiogram. Eur Respir J 1995; 8: 546-550
• 21 Franklin KA, Nilsson JB, Sahlin C et al. Sleep apnoea and nocturnal angina. Lancet 1995; 345: 1085-1087
• 22 Valipour A, McGown AD, Makker H et al. Some factors affecting cerebral tissue saturation during obstructive sleep apnoea. Eur Respir J 2002; 20: 444-450
• 23 Podszus T, Bauer W, Mayer J et al. Sleep apnea and pulmonary hypertension. Klin Wochenschr 1986; 64: 131-134
• 24 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: 934-939
• 25 Schulz R, Mahmoudi S, Hattar K et al. Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 2000; 162: 566-570
• 26 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: 824-830
• 27 Minoguchi K, Tazaki T, Yokoe T et al. Elevated production of tumor necrosis factor-alpha by monocytes in patients with obstructive sleep apnea syndrome. Chest 2004; 126: 1473-1479
• 28 Minoguchi K, Yokoe T, Tazaki T et al. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med 2005; 172: 625-630
• 29 Allahdadi KJ, Walker BR, Kanagy NL. Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension. Hypertension 2005; 45: 705-709
• 30 Phillips BG, Narkiewicz K, Pesek CA et al. Effects of obstructive sleep apnea on endothelin-1 and blood pressure. J Hypertens 1999; 17: 61-66
• 31 Grimpen F, Kanne P, Schulz E et al. Endothelin-1 plasma levels are not elevated in patients with obstructive sleep apnea. Eur Respir J 2000; 15: 320-325
• 32 Wessendorf TE, Thilmann AF, Wang YM et al. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 2000; 162: 2039-2042
• 33 Mehra R, Xu F, Babineau DC et al. Sleep-disordered breathing and prothrombotic biomarkers: cross-sectional results of the Cleveland Family Study. Am J Respir Crit Care Med 2010; 182: 826-833
• 34 Phillips CL, McEwen BJ, Morel-Kopp MC et al. Effects of continuous positive airway pressure on coagulability in obstructive sleep apnoea: a randomised, placebo-controlled crossover study. Thorax 2012; 67: 639-644
• 35 Carlson JT, Hedner J, Elam M et al. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest 1993; 103: 1763-1768
• 36 Somers VK, Dyken ME, Clary MP et al. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995; 96: 1897-1904
• 37 Donadio V, Liguori R, Vetrugno R et al. Daytime sympathetic hyperactivity in OSAS is related to excessive daytime sleepiness. J Sleep Res 2007; 16: 327-332
• 38 Andreas S, Eichele G. Sleep apnea – time to consider clock genes. Eur Respir J 2008; 32: 1-2
• 39 Andreas S, Anker SD, Scanlon PD et al. Neurohumoral activation as a link to systemic manifestation of chronic lung disease. Chest 2005; 128: 3618-3624
• 40 Ip MS, Lam B, Chan LY et al. Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure. Am J Respir Crit Care Med 2000; 162: 2166-2171
• 41 Takase B, Akima T, Uehata A et al. Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans. Clin Cardiol 2004; 27: 223-227
• 42 Patt BT, Jarjoura D, Haddad DN et al. Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea. Am J Respir Crit Care Med 2010; 182: 1540-1545
• 43 Drager LF, Bortolotto LA, Figueiredo AC et al. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 2007; 176: 706-712
• 44 Peters A, Kubera B, Hubold C et al. The selfish brain: stress and eating behavior. Front Neurosci 2011; 5: 74
• 45 Schulz R, Eisele HJ, Reichenberger F et al. [Obstructive sleep apnoea and metabolic syndrome]. Pneumologie 2008; 62: 88-91
• 46 Sharma SK, Agrawal S, Damodaran D et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med 2011; 365: 2277-2286
• 47 Andreas S. Nocturnal insights in chronic heart failure. Eur Heart J 1999; 20: 1140-1141
• 48 Spicuzza L, Bernardi L, Calciati A et al. Autonomic modulation of heart rate during obstructive versus central apneas in patients with sleep-disordered breathing. Am J Respir Crit Care Med 2003; 167: 902-910
• 49 Brooks D, Horner RL, Kozar LF et al. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model [see comments]. J Clin Invest 1997; 99: 106-109
• 50 Bazzano LA, Khan Z, Reynolds K et al. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 2007; 50: 417-423
• 51 Haentjens P, Van Meerhaeghe A, Moscariello A et al. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med 2007; 167: 757-764
• 52 Montserrat JM, Garcia-Rio F, Barbe F. Diagnostic and therapeutic approach to nonsleepy apnea. Am J Respir Crit Care Med 2007; 176: 6-9
• 53 Marin JM, Carrizo SJ, Vicente E et al. 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; 365: 1046-1053
• 54 Young T, Finn L, Peppard PE et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008; 31: 1071-1078
• 55 Buchner NJ, Sanner BM, Borgel J et al. Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. Am J Respir Crit Care Med 2007; 176: 1274-1280
• 56 Lavie P, Lavie L. Unexpected survival advantage in elderly people with moderate sleep apnoea. J Sleep Res 2009; 18: 397-403
• 57 Punjabi NM, Caffo BS, Goodwin JL et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 2009; 6: e1000132
• 58 Shahar E, Whitney CW, Redline S 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: 19-25
• 59 Kaneko Y, Floras JS, Usui K et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003; 348: 1233-1241
• 60 Smith LA, Vennelle M, Gardner RS et al. Auto-titrating continuous positive airway pressure therapy in patients with chronic heart failure and obstructive sleep apnoea: a randomized placebo-controlled trial. Eur Heart J 2007; 28: 1221-1227
• 61 Javaheri S, Caref EB, Chen E et al. Sleep apnea testing and outcomes in a large cohort of Medicare beneficiaries with newly diagnosed heart failure. Am J Respir Crit Care Med 2011; 183: 539-546
• 62 Dickstein K, Cohen-Solal A, Filippatos G et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29: 2388-2442
• 63 Wachter R, Luthje L, Klemmstein D et al. Impact of obstructive sleep apnoea on diastolic function. Eur Respir J 2012; in press
• 64 Arias MA, Garcia-Rio F, Alonso-Fernandez A et al. Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men. Circulation 2005; 112: 375-383
• 65 Nieto FJ, Young TB, Lind BK et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000; 283: 1829-1836
• 66 Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J 2006; 28: 596-602
• 67 Cassar A, Morgenthaler TI, Lennon RJ et al. Treatment of obstructive sleep apnea is associated with decreased cardiac death after percutaneous coronary intervention. J Am Coll Cardiol 2007; 50: 1310-1314
• 68 Peker Y, Glantz H, Thunstrom E et al. Rationale and design of the Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnoea--RICCADSA trial. Scand Cardiovasc J 2009; 43: 24-31
• 69 Redline S, Yenokyan G, Gottlieb DJ et al. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med 2010; 182: 269-277
• 70 Wessendorf TE, Wang YM, Thilmann AF et al. Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke. Eur Respir J 2001; 18: 623-629
• 71 Martinez-Garcia MA, Campos-Rodriguez F, Soler-Cataluna JJ et al. Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment. Eur Respir J 2012; 39: 906-912
• 72 Dyken ME, Im KB. Obstructive sleep apnea and stroke. Chest 2009; 136: 1668-1677
• 73 Mason RH, Ruegg G, Perkins J et al. Obstructive sleep apnea in patients with abdominal aortic aneurysms: highly prevalent and associated with aneurysm expansion. Am J Respir Crit Care Med 2011; 183: 668-674
• 74 Gami AS, Howard DE, Olson EJ et al. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med 2005; 352: 1206-1214
• 75 Kanagala R, Murali NS, Friedman PA et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation 2003; 107: 2589-2594
• 76 Arzt M, Luigart R, Schum C et al. Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism. Eur Respir J 2012; 40: 919-924
• 77 Hoeper MM, Andreas S, Bastian A et al. Pulmonary hypertension due to chronic lung disease: Updated Recommendations of the Cologne Consensus Conference 2011. Int J Cardiol 2011; 154: S45-S53
• 78 Schulz R, Eisele HJ, Weissmann N et al. Pulmonale Hypertonie und schlafbezogene Atemstörung. Pneumologie 2005; 59: 270-274
• 79 Johansson K, Neovius M, Lagerros YT et al. Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial. Bmj 2009; 339: b4609
• 80 Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA 2004; 291: 2013-2016
• 81 Franklin KA, Gislason T, Omenaas E et al. The influence of active and passive smoking on habitual snoring. Am J Respir Crit Care Med 2004; 170: 799-803
• 82 Knuiman M, James A, Divitini M et al. Longitudinal study of risk factors for habitual snoring in a general adult population: the Busselton Health Study. Chest 2006; 130: 1779-1783
• 83 Peppard PE, Young T. Exercise and sleep-disordered breathing: an association independent of body habitus. Sleep 2004; 27: 480-484
• 84 Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 2003; 290: 1906-1914