Obstructive sleep apnea syndrome and fatty liver: Association or causal link?

World Journal of Gastroenterology

Volumn 16, Issue 34, 2010, Pages 4243-4252

  Ahmed, Mohamed H ^a   Byrne, Christopher D ^a  

^a UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Hyperlipidemia; Insulin resistance; Non alcoholic fatty liver disease; Sleep apnea syndrome

Indexed keywords

ADIPONECTIN; FATTY ACID; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 6; LEPTIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TUMOR NECROSIS FACTOR ALPHA;

ADIPOSE TISSUE; ARTICLE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; DISEASE ASSOCIATION; DISEASE COURSE; ENDOPLASMIC RETICULUM STRESS; GLUCOSE INTOLERANCE; HUMAN; HYPERLIPIDEMIA; HYPOXIA; INFLAMMATION; INSULIN RESISTANCE; METABOLIC SYNDROME X; NONALCOHOLIC FATTY LIVER; OBESITY; SLEEP APNEA SYNDROME;

EID: 77957569174     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v16.i34.4243     Document Type: Article

References (105)

1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle ged adults. N Engl J Med 1993; 328: 1230-1235
2. Sleep-related breathing disorders in adults: recommendations for Syndrome definition and measurement techniques in clinical research. The Report of an American Academy of leep Medicine Task Force. Sleep 1999; 22: 667-689
3. Botros N, Concato J, Mohsenin V, Selim B, Doctor K, Yaggi K. Obstructive sleep apnea as a risk factor for type 2 diabetes. Am J Med 2009; 122: 1122-1127
4. Minoguchi K, Yokoe T, Tanaka A, Ohta S, Hirano T, Yoshino G, O'Donnell CP, Adachi M. Association between lipid eroxidation and inflammation in obstructive sleep apnoea. Eur Respir J 2006; 28: 378-385
5. Byrne CD. Hypoxia and non-alcoholic fatty liver disease. Clin Sci (Lond) 2009; 118: 397-400
6. Ahmed MH, Abu EO, Byrne CD. Non-Alcoholic Fatty Liver Disease (NAFLD): New challenge for general practitioners and important burden for health authorities? Prim Care Diabetes 2010; Epub ahead of print
7. Byrne CD, Olufadi R, Bruce KD, Cagampang FR, Ahmed MH. Metabolic disturbances in non-alcoholic fatty liver disease. Clin Sci (Lond) 2009; 116: 539-564
8. Ahmed MH, Byrne CD. Non Alcoholic Steatohepatitis and Metabolic syndrome. In: Byrne C, Wild S, editors. Metabolic syndrome. Chichester, UK: John Wiley & Sons, 2005: 279-305
9. Ahmed MH, Byrne CD. Metabolic syndrome, diabetes & CHD risk. In: Packard CJ, editor. The Year in Lipid Disorders. Oxford, UK: Clinical Publishing, 2007: 3-26
10. Ahmed MH. Biochemical markers: the road map for the diagnosis of nonalcoholic fatty liver disease. Am J Clin Pathol 2007; 127: 20-22
11. Nishibayashi M, Miyamoto M, Miyamoto T, Suzuki K, Hirata K. Correlation between severity of obstructive sleep apnea and prevalence of silent cerebrovascular lesions. J Clin Sleep Med 2008; 4: 242-247
12. Dorkova Z, Petrasova D, Molcanyiova A, Popovnakova M, Tkacova R. Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome. Chest 2008;134: 686-692
13. Takama N, Kurabayashi M. Influence of untreated sleep disordered breathing on the long-term prognosis of patients with cardiovascular disease. Am J Cardiol 2009; 103: 730-734
14. Savransky V, Nanayakkara A, Vivero A, Li J, Bevans S, Smith PL, Torbenson MS, Polotsky VY. Chronic intermittent hypoxia predisposes to liver injury. Hepatology 2007; 45:1007-1013
15. Savransky V, Bevans S, Nanayakkara A, Li J, Smith PL, Torbenson MS, Polotsky VY. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol 2007; 293: G871-G877
16. Takayama F, Egashira T, Kawasaki H, Mankura M, Nakamoto K, Okada S, Mori A. A Novel Animal Model of Non-alcoholic Steatohepatitis (NASH): Hypoxemia Enhances the Development of NASH. J Clin Biochem Nutr 2009; 45: 335-340
17. Piguet AC, Stroka D, Zimmermann A, Dufour JF. Hypoxia aggravates non-alcoholic steatohepatitis in mice lacking hepatocellular PTEN. Clin Sci (Lond) 2009; 118: 401-410
18. Chin K, Nakamura T, Takahashi K, Sumi K, Ogawa Y, Masuzaki H, Muro S, Hattori N, Matsumoto H, Niimi A, Chiba T, Nakao K, Mishima M, Ohi M, Nakamura T. Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients. Am J Med 2003; 114: 370-376
19. Kohler M, Pepperell JC, Davies RJ, Stradling JR. Continuous positive airway pressure and liver enzymes in obstructive sleep apnoea: data from a randomized controlled trial. Respiration 2009; 78: 141-146
20. Jouët P, Sabaté JM, Maillard D, Msika S, Mechler C, Ledoux S, Harnois F, Coffin B. Relationship between obstructive sleep apnea and liver abnormalities in morbidly obese patients: a prospective study. Obes Surg 2007; 17: 478-485
21. Kallwitz ER, Herdegen J, Madura J, Jakate S, Cotler SJ. Liver enzymes and histology in obese patients with obstructive sleep apnea. J Clin Gastroenterol 2007; 41: 918-921
22. Mishra P, Nugent C, Afendy A, Bai C, Bhatia P, Afendy M, Fang Y, Elariny H, Goodman Z, Younossi ZM. Apnoeic- hypopnoeic episodes during obstructive sleep apnoea are associated with histological nonalcoholic steatohepatitis. Liver Int 2008; 28: 1080-1086
23. Polotsky VY, Patil SP, Savransky V, Laffan A, Fonti S, Frame LA, Steele KE, Schweizter MA, Clark JM, Torbenson MS, Schwartz AR. Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. Am J Respir Crit Care Med 2009; 179: 228-234
24. Norman D, Bardwell WA, Arosemena F, Nelesen R, Mills PJ, Loredo JS, Lavine JE, Dimsdale JE. Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea. Sleep 2008; 31: 121-126
25. Kheirandish-Gozal L, Sans Capdevila O, Kheirandish E, Gozal D. Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea. Chest 2008; 133: 92-99
26. Byrne CD. Fatty liver: role of inflammation and fatty acid nutrition. Prostaglandins Leukot Essent Fatty Acids 2010; 82: 265-271
27. Idris I, Hall AP, O'Reilly J, Barnett A, Allen M, Andrews R, Grunstein P, Lewis K, Goenka N, Wilding JP. Obstructive sleep apnoea in patients with type 2 diabetes: aetiology and implications for clinical care. Diabetes Obes Metab 2009; 11: 733-741
28. Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A, Lin HM, Kales A, Chrousos GP. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000; 85: 1151-1158
29. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL. Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 2002; 165: 677-682
30. Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002; 165: 670-676
31. Meslier N, Gagnadoux F, Giraud P, Person C, Ouksel H, Urban T, Racineux JL. Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Respir J 2003; 22: 156-160
32. West SD, Nicoll DJ, Stradling JR. Prevalence of obstructive sleep apnoea in men with type 2 diabetes. Thorax 2006; 61: 945-950
33. Mallon L, Broman JE, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population. Diabetes Care 2005; 28: 2762-2767
34. Tuomilehto H, Peltonen M, Partinen M, Seppä J, Saaristo T, Korpi-Hyövälti E, Oksa H, Puolijoki H, Saltevo J, Vanhala M, Tuomilehto J. Sleep duration is associated with an increased risk for the prevalence of type 2 diabetes in middle-aged women - The FIN-D2D survey. Sleep Med 2008; 9: 221-227
35. Polotsky VY, Li J, Punjabi NM, Rubin AE, Smith PL, Schwartz AR, O'Donnell CP. Intermittent hypoxia increases insulin resistance in genetically obese mice. J Physiol 2003; 552: 253-264
36. Iiyori N, Alonso LC, Li J, Sanders MH, Garcia-Ocana A, O'Doherty RM, Polotsky VY, O'Donnell CP. Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. Am J Respir Crit Care Med 2007; 175: 851-857
37. Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes (Lond) 2009; 33: 54-66
38. Yin J, Gao Z, He Q, Zhou D, Guo Z, Ye J. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am J Physiol Endocrinol Metab 2009; 296: E333-E342
39. Williams A, Scharf SM. Obstructive sleep apnea, cardio-vascular disease, and inflammation--is NF-kappaB the key? Sleep Breath 2007; 11: 69-76
40. Htoo AK, Greenberg H, Tongia S, Chen G, Henderson T, Wilson D, Liu SF. Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation. Sleep Breath 2006; 10: 43-50
41. Greenberg H, Ye X, Wilson D, Htoo AK, Hendersen T, Liu SF. Chronic intermittent hypoxia activates nuclear factor- kappaB in cardiovascular tissues in vivo. Biochem Biophys Res Commun 2006; 343: 591-596
42. Selmi C, Montano N, Furlan R, Keen CL, Gershwin ME. Inflammation and oxidative stress in obstructive sleep apnea syndrome. Exp Biol Med (Maywood) 2007; 232: 1409-1413
43. Yamauchi M, Tamaki S, Tomoda K, Yoshikawa M, Fukuoka A, Makinodan K, Koyama N, Suzuki T, Kimura H. Evidence for activation of nuclear factor kappaB in obstructive sleep apnea. Sleep Breath 2006; 10: 189-193
44. Tasali E, Ip MS. Obstructive sleep apnea and metabolic syndrome: alterations in glucose metabolism and inflammation. Proc Am Thorac Soc 2008; 5: 207-217
45. Foufelle F, Ferré P. [Regulation of carbohydrate metabolism by insulin: role of transcription factor SREBP-1c in the hepatic transcriptional effects of the hormone] J Soc Biol 2001; 195: 243-248
46. Ahmed MH, Byrne CD. Modulation of sterol regulatory element binding proteins (SREBPs) as potential treatments for non-alcoholic fatty liver disease (NAFLD). Drug Discov Today 2007; 12: 740-747
47. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002; 53: 409-435
48. Ferré P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 2004; 53 Suppl 1: S43-S50
49. Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptoralpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol 2006; 169: 846-860
50. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005; 1: 15-25
51. Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002; 13: 84-89
52. Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 2002; 51: 1884-1888
53. Savvidou S, Hytiroglou P, Orfanou-Koumerkeridou H, Panderis A, Frantzoulis P, Goulis J. Low serum adiponectin levels are predictive of advanced hepatic fibrosis in patients with NAFLD. J Clin Gastroenterol 2009; 43: 765-772
54. Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, Shimomura I. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007; 56: 901-911
55. Chen B, Lam KS, Wang Y, Wu D, Lam MC, Shen J, Wong L, Hoo RL, Zhang J, Xu A. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes. Biochem Biophys Res Commun 2006; 341: 549-556
56. Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003; 301: 1045-1050
57. Snyder EM, Carr RD, Deacon CF, Johnson BD. Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans. Appl Physiol Nutr Metab 2008; 33: 929-935
58. Grosfeld A, Andre J, Hauguel-De Mouzon S, Berra E, Pouyssegur J, Guerre-Millo M. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J Biol Chem 2002; 277: 42953-42957
59. Sanner BM, Kollhosser P, Buechner N, Zidek W, Tepel M. Influence of treatment on leptin levels in patients with obstructive sleep apnoea. Eur Respir J 2004; 23: 601-604
60. Kapsimalis F, Varouchakis G, Manousaki A, Daskas S, Nikita D, Kryger M, Gourgoulianis K. Association of sleep apnea severity and obesity with insulin resistance, C-reactive protein, and leptin levels in male patients with obstructive sleep apnea. Lung 2008; 186: 209-217
61. Ulukavak Ciftci T, Kokturk O, Bukan N, Bilgihan A. Leptin and ghrelin levels in patients with obstructive sleep apnea syndrome. Respiration 2005; 72: 395-401
62. Yasumasu T, Takahara K, Nakashima Y. Hypoxia inhibits leptin production by cultured rat adipocytes. Obes Res 2002; 10: 128
63. Schmoller A, Voss M, Gehring H, Rudolf S, Schweiger U, Schultes B, Oltmanns KM. Short Hypoxia Does not Affect Plasma Leptin in Healthy Men under Euglycemic Clamp Conditions. Int J Endocrinol 2009; 2009: 270698
64. Chaiban JT, Bitar FF, Azar ST. Effect of chronic hypoxia on leptin, insulin, adiponectin, and ghrelin. Metabolism 2008; 57: 1019-1022
65. Keijer J, van Schothorst EM. Adipose tissue failure and mitochondria as a possible target for improvement by bioactive food components. Curr Opin Lipidol 2008; 19: 4-10
66. Bruce KD, Cagampang FR, Argenton M, Zhang J, Ethirajan PL, Burdge GC, Bateman AC, Clough GF, Poston L, Hanson MA, McConnell JM, Byrne CD. Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology 2009; 50: 1796-1808
67. Nakatani Y, Kaneto H, Kawamori D, Yoshiuchi K, Hatazaki M, Matsuoka TA, Ozawa K, Ogawa S, Hori M, Yamasaki Y, Matsuhisa M. Involvement of endoplasmic reticulum stress in insulin resistance and diabetes. J Biol Chem 2005; 280: 847-851
68. Ozawa K, Miyazaki M, Matsuhisa M, Takano K, Nakatani Y, Hatazaki M, Tamatani T, Yamagata K, Miyagawa J, Kitao Y, Hori O, Yamasaki Y, Ogawa S. The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes 2005; 54: 657-663
69. Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, Koromilas A, Wouters BG. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. Mol Cell Biol 2002; 22: 7405-7416
70. Gentile CL, Pagliassotti MJ. The role of fatty acids in the development and progression of nonalcoholic fatty liver disease. J Nutr Biochem 2008; 19: 567-576
71. Ahmed MH, Byrne CD. Current treatment of non-alcoholic fatty liver disease. Diabetes Obes Metab 2009; 11: 188-195
72. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
73. Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 2005; 9: 211-224
74. Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004; 25: 735-741
75. Tkacova R, Dorkova Z, Molcanyiova A, Radikova Z, Klimes I, Tkac I. Cardiovascular risk and insulin resistance in patients with obstructive sleep apnea. Med Sci Monit 2008; 14: CR438-CR444
76. Sasanabe R, Banno K, Otake K, Hasegawa R, Usui K, Morita M, Shiomi T. Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome. Hypertens Res 2006; 29: 315-322
77. Lam JC, Lam B, Lam CL, Fong D, Wang JK, Tse HF, Lam KS, Ip MS. Obstructive sleep apnea and the metabolic syndrome in community-based Chinese adults in Hong Kong. Respir Med 2006; 100: 980-987
78. Shiina K, Tomiyama H, Takata Y, Usui Y, Asano K, Hirayama Y, Nakamura T, Yamashina A. Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study. Hypertens Res 2006; 29: 433-441
79. Antonopoulos S, Mikros S, Mylonopoulou M, Kokkoris S, Giannoulis G. Rosuvastatin as a novel treatment of non- alcoholic fatty liver disease in hyperlipidemic patients. Atherosclerosis 2006; 184: 233-234
80. Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, Zenari L, Falezza G. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005; 54: 3541-3546
81. Targher G, Bertolini L, Padovani R, Rodella S, Zoppini G, Zenari L, Cigolini M, Falezza G, Arcaro G. Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease. Diabetes Care 2006; 29: 1325-1330
82. Targher G, Bertolini L, Padovani R, Poli F, Scala L, Tessari R, Zenari L, Falezza G. Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non-alcoholic fatty liver disease. Diabet Med 2006; 23: 403-409
83. Targher G, Bertolini L, Padovani R, Poli F, Scala L, Zenari L, Zoppini G, Falezza G. Non-alcoholic fatty liver disease is associated with carotid artery wall thickness in diet-controlled type 2 diabetic patients. J Endocrinol Invest 2006; 29: 55-60
84. Targher G, Bertolini L, Rodella S, Tessari R, Zenari L, Lippi G, Arcaro G. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 2007; 30: 2119-2121
85. Targher G, Bertolini L, Rodella S, Zoppini G, Zenari L, Falezza G. Associations between liver histology and cortisol secretion in subjects with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 2006; 64: 337-341
86. Targher G, Zoppini G, Lippi G, Guidi GC, Muggeo M. Effect of serum gamma-glutamyltransferase and obesity on the risk of dyslipidemia and poor glycemic control in type 2 diabetic patients: cross-sectional findings from the Verona Diabetes Study. Clin Chem 2007; 53: 1867-1869; author reply 1869-1870
87. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, Day C, Arcaro G. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007; 30: 1212-1218
88. Lévy P, Pépin JL, Arnaud C, Baguet JP, Dematteis M, Mach F. Obstructive sleep apnea and atherosclerosis. Prog Cardiovasc Dis 2009; 51: 400-410
89. Tomásová H, Lisý V, Trojan S, Stastný F. Effect of shortterm or intermittent hypobaric hypoxia on plasma lipids in young rats. Physiol Bohemoslov 1987; 36: 361-364
90. Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, Marino RL, Rodriguez A, Hubbard WC, O'Donnell CP, Polotsky VY. Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 2005; 97: 698-706
91. Li J, Nanayakkara A, Jun J, Savransky V, Polotsky VY. Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia. Physiol Genomics 2007; 31: 273-280
92. Savransky V, Nanayakkara A, Li J, Bevans S, Smith PL, Rodriguez A, Polotsky VY. Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med 2007; 175: 1290-1297
93. Savransky V, Jun J, Li J, Nanayakkara A, Fonti S, Moser AB, Steele KE, Schweitzer MA, Patil SP, Bhanot S, Schwartz AR, Polotsky VY. Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deficiency of stearoyl coenzyme A desaturase. Circ Res 2008; 103: 1173-1180
94. Li J, Bosch-Marce M, Nanayakkara A, Savransky V, Fried SK, Semenza GL, Polotsky VY. Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha. Physiol Genomics 2006; 25: 450-457
95. Steiropoulos P, Tsara V, Nena E, Fitili C, Kataropoulou M, Froudarakis M, Christaki P, Bouros D. 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
96. Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 2004; 59: 777-782
97. Gozal D, O'Brien LM. Snoring and obstructive sleep apnoea in children: why should we treat? Paediatr Respir Rev 2004; 5 Suppl A: S371-S376
98. Bradley TD, Floras JS. Obstructive sleep apnoea and its car diovascular consequences. Lancet 2009; 373: 82-93
99. Fletcher EC, DeBehnke RD, Lovoi MS, Gorin AB. Undiagnosed sleep apnea in patients with essential hypertension. Ann Intern Med 1985; 103: 190-195
100. Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, Leung RS, Bradley TD. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. JHypertens 2001; 19: 2271-2277
101. Börgel J, Sanner BM, Keskin F, Bittlinsky A, Bartels NK, Büchner N, Huesing A, Rump LC, Mügge A. Obstructive sleep apnea and blood pressure. Interaction between the blood pressure-lowering effects of positive airway pressure therapy and antihypertensive drugs. Am J Hypertens 2004; 17: 1081-1087
102. Peker Y, Kraiczi H, Hedner J, Löth S, Johansson A, Bende M. An independent association between obstructive sleep apnoea and coronary artery disease. Eur Respir J 1999; 14: 179-184
103. Mooe T, Franklin KA, Holmström K, Rabben T, Wiklund U. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med 2001; 164: 1910-1913
104. Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S. Sleep disordered breathing and poor functional outcome after stroke. Stroke 1996; 27: 252-259
105. Kaneko Y, Hajek VE, Zivanovic V, Raboud J, Bradley TD. Relationship of sleep apnea to functional capacity and length of hospitalization following stroke. Sleep 2003; 26:293-297