Obstruktive Schlaf-Apnoe und metabolisches Syndrom

Zusammenfassung

Das metabolische Syndrom, d. h. das kombinierte Auftreten von Adipositas, erhöhtem Blutdruck, Insulinresistenz und Dyslipidämie (erhöhte Triglyceride, erniedrigtes HDL-Cholesterin), ist mit einer deutlichen Erhöhung des kardiovaskulären Risikos verbunden. Patienten mit obstruktiver Schlaf-Apnoe (OSA) weisen sehr häufig ein metabolisches Syndrom auf. Die Adipositas gilt als Hauptrisikofaktor der OSA und die OSA selbst wird jetzt als häufigste Ursache der sekundären arteriellen Hypertonie angesehen. Die Kausalität der Beziehungen zwischen OSA und metabolischen Veränderungen ist aufgrund des Einflusses der Variable „Adipositas” weniger gut etabliert, jedoch sprechen epidemiologische Untersuchungen zumindest für eine unabhängige Assoziation zwischen OSA und Insulinresistenz. Die CPAP-Therapie kann die OSA-assoziierte arterielle Hypertonie günstig beeinflussen, ob und in welchem Umfang dadurch auch Insulinresistenz und Dyslipidämie gebessert werden können, muss hingegen noch durch Plazebo-kontrollierte, randomisierte Langzeit-Studien mit ausreichend hohen Patientenzahlen geklärt werden.

Abstract

Metabolic syndrome, i. e., the combined occurrence of obesity, arterial hypertension, insulin resistance and dyslipidaemia (increased triglycerides, reduced HDL cholesterol), is associated with a marked increase in cardiovascular risk. The prevalence of metabolic syndrome in patients with obstructive sleep apnoea (OSA) is very high. Obesity is the main risk factor for OSA and OSA itself is now considered to be the most frequent cause of secondary arterial hypertension. Due to the confounding influence of obesity, the causal connection between OSA and metabolic disturbances is less well established, however, epidemiological data are at least in favour of an independent link between OSA and insulin resistance. It is known that CPAP therapy can ameliorate OSA-associated hypertension. In contrast, the effects of CPAP treatment on insulin resistance and dyslipidaemia have to be further elucidated by large, randomised interventional trials.

Literatur

• 1 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults . Executive Summary of The Third Report of The National Cholesterol Education Programm (NCEP) Expert Panel of Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III).  JAMA. 2001;  285 2486-2497
• 2 Grundy S M, Cleeman J I, Daniels S R. et al . American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.  Circulation. 2005;  112 2735-2752
• 3 Alberti K G, Zimmet P, Shaw J. IDF Epidemiology Task Force Consensus Group. The metabolic syndrome - a new worldwide definition.  Lancet. 2005;  366 1059-1062
• 4 Coughlin S R, Mawdsley L, Mugarza J A. et al . Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome.  Eur Heart J. 2004;  25 735-741
• 5 Prugger C, Keil U. Entwicklung der Adipositas in Deutschland - Größenordnung, Determinanten und Perspektiven.  Dtsch Med Wochenschr. 2007;  132 892-897
• 6 Gami A S, Caples S M, Somers V K. Obesity and obstructive sleep apnea.  Endocrinol Metab Clin N Am. 2003;  32 869-894
• 7 Schwab R, Pasirstein M, Pierson R. et al . Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging.  Am J Respir Crit Care Med. 2003;  168 522-530
• 8 Schwab R, Pasirstein M, Kaplan L. et al . Family aggregation of upper airway soft tissue structures in normal subjects and patients with sleep apnea.  Am J Respir Crit Care Med. 2006;  173 453-463
• 9 Young T, Shahar E, Nieto F J. et al . Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study.  Arch Intern Med. 2002;  162 893-900
• 10 Taheri S, Lin L, Austin D. et al . Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index.  PLoS Med. 2004;  (3) e62
• 11 Schädlich S, Boldemann R D, Blankenburg T h. et al . Gewichtsveränderung unter langfristiger CPAP-Therapie - eine retrospektive Analyse an 244 Patienten.  Somnologie. 2006;  10 15-20
• 12 Chin K, Shinizu K, Nakamura T. et al . Changes in intraabdominal fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy.  Circulation. 1999;  100 706-712
• 13 Young T, Peppard P E, Gottlieb D J. Epidemiology of obstructive sleep apnea: a population health perspective.  Am J Respir Crit Care Med. 2002;  165 1217-1239
• 14 Dixon J B, Schachter L M, O’Brien P E. Polysomnography before and after weight loss in obese patients with severe sleep apnea.  Int J Obes (Lond). 2005;  9 1048-1054
• 15 Haines K L, Nelson L G, Gonzalez R. et al . Objective evidence that bariatric surgery improves obesity-related obstructive sleep apnea.  Surgery. 2007;  3 354-358
• 16 Millman R P, Redline S, Carlisle C C. et al . Daytime hypertension in obstructive sleep apnea. Prevalence and contributing risk factors.  Chest. 1991;  99 861-866
• 17 Lavie P, Ben-Yosef R, Rubin A E. Prevalence of sleep apnea syndrome among patients with essential hypertension.  Am Heart J. 1984;  108 373-376
• 18 Davies C W, Crosby J H, Mullins R L. et al . Case-control study of 24 hour ambulatory blood pressure in patients with obstructive sleep apnoea and normal matched control subjects.  Thorax. 2000;  55 736-740
• 19 Logan A G, Perlikowski S M, Mente A. et al . High prevalence of unrecognized sleep apnoea in drug-resistant hypertension.  J Hypertens. 2001;  19 2271-2277
• 20 Peppard P E, Young T, Palta M. et al . Prospective study of the association between sleep-disordered breathing and hypertension.  N Engl J Med. 2000;  342 1378-1384
• 21 Narkiewicz K, Somers V K. The sympathetic nervous system and obstructive sleep apnea: implications for hypertension.  J Hypertens. 1997;  15 1613-1619
• 22 Gjørup P H, Sadauskiene L, Wessels J. et al . Abnormally increased endothelin-1 in plasma during the night in obstructive sleep apnea: relation to blood pressure and severity of disease.  Am J Hypertens. 2007;  20 44-52
• 23 Møller D S, Lind P, Strunge B, Pedersen E B. Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea.  Am J Hypertens. 2003;  16 274-280
• 24 Schulz R, Schmidt D, Blum A. et al . Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnoea-response to CPAP therapy.  Thorax. 2000;  55 1046-1051
• 25 Bazzano L A, 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
• 26 Chobanian A V, Bakris G L, Black H R. et al . The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.  JAMA. 2003;  289 2560-2572
• 27 Reichmuth K J, Austin D, Skatrud J B. et al . Association of sleep apnea and type II diabetes: a population-based study.  Am J Respir Crit Care Med. 2005;  172 1950-1955
• 28 Meslier N, Gagnadoux F, Giraud P. et al . Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome.  Eur Respir J. 2003;  22 156-160
• 29 West S D, Nicoll D J, Stradling J R. Prevalence of obstructive sleep apnoea in men with type 2 diabetes.  Thorax. 2006;  61 945-950
• 30 Punjabi N M, Sorkin J D, Katzel L I. et al . Sleep-disordered breathing and insulin resistance in middle-aged and overweight men.  Am J Respir Crit Care Med. 2002;  165 677-682
• 31 Ip M S, Lam B, Ng M M. et al . Obstructive sleep apnea is independently associated with insulin resistance.  Am J Respir Crit Care Med. 2002;  165 670-676
• 32 Furukawa S, Fujita T, Shimabukuro M. et al . Increased oxidative stress in obesity and its impact on metabolic syndrome.  J Clin Invest. 2004;  114 1752-1761
• 33 Vgontzas A N, Papanicolaou D A, Bixler E O. et al . Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity.  J Clin Endocrinol Metab. 1997;  82 1313-1316
• 34 Guerre-Millo M. Adipose tissue and adipokines: for better or worse.  Diabetes Metab. 2004;  30 13-19
• 35 Ip M S, Lam K S, Ho C. et al . Serum leptin and vascular risk factors in obstructive sleep apnea.  Chest. 2000;  118 580-586
• 36 Zhang X L, Yin K S, Wang H. et al . Serum adiponectin levels in adult male patients with obstructive sleep apnea hypopnea syndrome.  Respiration. 2006;  73 73-77
• 37 Wolk R, Svatikova A, Nelson C A. et al . Plasma levels of adiponectin, a novel adipocyte-derived hormone, in sleep apnea.  Obes Res. 2005;  13 186-190
• 38 Harsch I A, Koebnick C, Wallaschofski H. et al . Resistin levels in patients with obstructive sleep apnoea syndrome - the link to subclinical inflammation?.  Med Sci Mon. 2004;  10 510-515
• 39 Spiegel K, Knutson K, Leproult R. et al . Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes.  J Appl Physiol. 2005;  99 2008-2019
• 40 Harsch I A, Schahin S P, Radespiel-Troger M. et al . Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome.  Am J Respir Crit Care Med. 2004;  169 156-162
• 41 Coughlin S R, Mawdsley L, Mugarza J A. et al . Cardiovascular and metabolic effects of CPAP in obese males with OSA.  Eur Respir J. 2007;  29 720-727
• 42 Brooks B, Cistulli P A, Borkman M. et al . Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness.  J Clin Endocrinol Metab. 1994;  79 1681-1685
• 43 Babu A R, Herdegen J, Fogelfeld L. et al . Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea.  Arch Intern Med. 2005;  165 447-452
• 44 Hassaballa H A, Tulaimat A, Herdegen J J. et al . The effect of continuous positive airway pressure on glucose control in diabetic patients with severe obstructive sleep apnea.  Sleep Breath. 2005;  9 176-180
• 45 Harsch I A, Schahin S P, Bruckner K. et al . The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes.  Respiration. 2004;  71 252-259
• 46 West S D, Nicoll D J, Wallace T M. et al . The effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes.  Thorax. 2007;  62 969-974
• 47 Lavie L, Perelman A, Lavie P. Plasma homocysteine levels in obstructive sleep apnea: association with cardiovascular morbidity.  Chest. 2001;  120 900-908
• 48 Can M, Acikgöz S, Mungan G. et al . Serum cardiovascular risk factors in obstructive sleep apnea.  Chest. 2006;  129 233-237
• 49 Sharma S K, Kumpawat S, Goel A. et al . Obesity, and not obstructive sleep apnea, is responsible for metabolic abnormalities in a cohort with sleep-disordered breathing.  Sleep Med. 2007;  8 12-17
• 50 McArdle N, Hillman D, Beilin L. et al . Metabolic risk factors for vascular disease in obstructive sleep apnea: a matched controlled study.  Am J Respir Crit Care Med. 2007;  175 190-195
• 51 Newman A B, Nieto F J, Guidry U. et al . Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study.  Am J Epidemiol. 2001;  154 50-59
• 52 Barcelo A, Miralles C, Barbe F. et al . Abnormal lipid peroxidation in patients with sleep apnoea.  Eur Respir J. 2000;  16 644-647
• 53 Lavie L, Vishnevsky A, Lavie P. Evidence for lipid peroxidation in obstructive sleep apnea.  Sleep. 2004;  27 123-128
• 54 Carpagnano G E, Kharitonov S A, 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 1386-1392
• 55 Tan K C, Chow W S, Lam J C. et al . HDL dysfunction in obstructive sleep apnea.  Atherosclerosis. 2006;  184 377-382
• 56 Iesato K, Tatsumi K, Saibara T. et al . Decreased lipoprotein lipase in obstructive sleep apnea syndrome.  Circ J. 2007;  71 1293-1298
• 57 Lattimore J D, Wilcox I, Nakhla S. et al . Repetitive hypoxia increases lipid loading in human macrophages - a potentially atherogenic effect.  Atherosclerosis. 2005;  179 255-259
• 58 Börgel J, Sanner B M, Bittlinsky A. et al . Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol levels.  Eur Respir J. 2006;  27 121-127
• 59 Steiropoulos P, Tsara V, Nena E. et al . Effect of continuous positive airway pressure treatment on serum cardiovascular risk factors in patients with obstructive sleep apnea-hypopnea syndrome.  Chest. 2007;  132 843-851
• 60 Robinson G V, Pepperell J C, Segal H C. et al . Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials.  Thorax. 2004;  59 777-782