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New Frontiers in Lifestyle-Related Diseases pp 107–114Cite as

Sleep Apnea Syndrome and Atherosclerosis

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Abstract

Obstructive sleep apnea (OSA) is a risk factor for a variety of cardiovascular diseases. Recent studies suggest that OSA is also independently associated with atherosclerosis. The intermittent hypoxia occurring in OSA patients has been proposed to represent a form of oxidative stress that causes generation of ROS and the development of systemic inflammation. We have reported that urinary levels of 8-isoprostane, a marker for oxidative stress, and serum levels of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and matrix metalloproteinsase-9, all markers for atherosclerosis, are elevated in patients with OSA. Moreover, carotid intima-media thickness and the percentage of silent brain infarction were significantly increased in patients with OSA compared to obese control subjects, consistent with the presence of atherosclerosis. Therefore, these results suggest that increased generation of ROS and development of systemic inflammation likely contribute to the progression of atherosclerosis in OSA.

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References

  • Aso Y, Okumura K, Takebayashi K, Wakabayashi S, Inukai T (2003) Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes. Diabetes Care 26:2622–2627

    Article  PubMed  Google Scholar 

  • Arzt M, Young T, Finn L, Skatrud JB, Bradley TD (2005) Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med 172:1447–1451

    Article  PubMed  Google Scholar 

  • Barks JL, McQuillan JJ, Iademarco MF (1997) TNF-and IL-4 synergistically increase vascular cell adhesion molecule-1 expression in cultured vascular smooth muscle cells. J Immunol 159:4532–4538

    PubMed  CAS  Google Scholar 

  • Brown DL, Hibbs MS, Kearney M, Loushin C, Isner JM (1995) Identification of 92-kD gelatinase in human coronary atherosclerotic lesions. Association of active enzyme synthesis with unstable angina. Circulation 91:2125–2131

    PubMed  CAS  Google Scholar 

  • Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G, Meyer J, Cambien F, Tiret L (2003) Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 107:1579–1585

    Article  PubMed  CAS  Google Scholar 

  • Cao JJ, Thach C, Manolio TA, Psaty BM, Kuller LH, Chaves PH, Polak JF, Sutton-Tyrrell K, Herrington DM, Price TR (2003) C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. Circulation 108:166–170

    Article  PubMed  CAS  Google Scholar 

  • Carrell TW, Burnand KG, Wells GM, Clements JM, Smith A (2002) Stromelysin-1 (matrix metalloproteinase-3) and tissue inhibitor of metalloproteinase-3 are overexpressed in the wall of abdominal aortic aneurysms. Circulation 105:477–482

    Article  PubMed  CAS  Google Scholar 

  • Dean RT, Wilcox I (1993) Possible atherogenic effects of hypoxia during obstructive sleep apnea. Sleep 16:S15–S22

    PubMed  CAS  Google Scholar 

  • Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165:934–939

    PubMed  Google Scholar 

  • Dhalla NS, Temsah RM, Netticadan T (2000) Role of oxidative stress in cardiovascular diseases. J Hypertens 18:655–673

    Article  PubMed  CAS  Google Scholar 

  • Ducharme A, Frantz S, Aikawa M, Rabkin E, Lindsey M, Rohde LE, Schoen FJ, Kelly RA, Werb Z, Libby P, Lee RT (2000) Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest 106:55–62.

    Article  PubMed  CAS  Google Scholar 

  • Dollery CM, McEvvan JR, Henney AM (1995) Matrix metalloproteinases and cardiovascular disease. Circ Res 77:863–868

    PubMed  CAS  Google Scholar 

  • Glass CK, Witztum JL (2001) Atherosclerosis: the road ahead. Cell 104:503–516

    Article  PubMed  CAS  Google Scholar 

  • Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB (1997) Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349:462–466

    Article  PubMed  CAS  Google Scholar 

  • Hatakeyama H, Nishizawa M, Nakagavva A, Nakano S, Kigoshi T, Uchida K (2002) Testosterone inhibits tumor necrosis factor-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells. FEBS Lett 530:129–132

    Article  PubMed  CAS  Google Scholar 

  • Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H (2003) Role of oxidative stress in atherosclerosis. Am J Cardiol 91:7A–11A

    Article  PubMed  CAS  Google Scholar 

  • Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH, Azen SP (1998) The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med 128:262–269

    PubMed  CAS  Google Scholar 

  • Kume N, Murase T, Moriwaki H, Aoyama T, Sawamura T, Masaki T, Kita T (1998) Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 83:322–327

    PubMed  CAS  Google Scholar 

  • Kaynak D, Goksan B, Kaynak H, Degirmenci N, Daglioglu S (2003) Is there a link between the severity of sleep-disordered breathing and atherosclerotic disease of the carotid arteries? Eur J Neurol 10:487–493

    Article  PubMed  CAS  Google Scholar 

  • Kossakowska AE, Edwards DR, Prusinkiewicz C, Zhang MC, Guo D, Urbanski SJ, Grogan T, Marquez LA, Janowska-Wieczorek A (1999) Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin’s lymphomas. Blood 94:2080–2089

    PubMed  CAS  Google Scholar 

  • Kondo S, Kubota S, Shimo T, Nishida T, Yosimichi G, Eguchi T, Sugahara T, Takigawa M (2002) Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases. Carcinogenesis 23:769–776

    Article  PubMed  CAS  Google Scholar 

  • Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl J Med 343:1139–1147

    Article  PubMed  CAS  Google Scholar 

  • Libby P, Ridker PM (1999) Novel inflammatory markers of coronary risk: theory versus practice. Circulation 100:1148–1150

    PubMed  CAS  Google Scholar 

  • Lavie L (2003) Obstructive sleep apnoea syndrome — oxidative stress disorder. Sleep Med Rev 7:35–51

    Article  PubMed  Google Scholar 

  • Lawson JA, Rokach J, FitzGerald GA (1999) Isoprostanes: formation, analysis and use as indices of lipid peroxidation in vivo. J Biol Chem 274:24441–24444

    Article  PubMed  CAS  Google Scholar 

  • Leonsson M, Hulthe J, Johannsson G, Wiklund O, Wikstrand J, Bengtsson BA, Oscarsson J (2003) Increased Interleukin-6 levels in pituitary-deficient patients are independently related to their carotid intima-media thickness. Clin Endocrinol 59:242–250

    Article  CAS  Google Scholar 

  • Magyar MT, Szikszai Z, Balla J, Valikovics A, Kappelmayer J, Imre S, Balla G, Jeney V, Csiba L, Bereczki D (2003) Early-onset carotid atherosclerosis is associated with increased intima-media thickness and elevated serum levels of inflammatory markers. Stroke 34:58–63

    Article  PubMed  CAS  Google Scholar 

  • Minoguchi K, Tazaki T, Yokoe K, Minoguchi H, Watanabe Y, Yamamoto M, Adachi M (2004) Elevated production of tumor necrosis factor-a by monocytes in patients with obstructive sleep apnea syndrome. Chest 126:1473–1479

    Article  PubMed  CAS  Google Scholar 

  • Minoguchi K, Yokoe T, Tanaka A, Ohta S, Hirano T, Yoshino G, O‘donnell CP, Adachi M (2006) Association between lipid peroxidation and inflammation in obstructive sleep apnoea. Eur Respir J 28:378–385

    Article  PubMed  CAS  Google Scholar 

  • Minoguchi K, Yokoe K, Tazaki T, Minoguchi H, Tanaka A, Oda N, Okada S, Ohta S., Naito H, Adachi M (2005) Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med 172:625–630

    Article  PubMed  Google Scholar 

  • Minoguchi K, Yokoe T, Tazaki T, Minoguchi H, Oda N, Tanaka A, Yamamoto M, Ohta S, O‘Donnell CP, Adachi M (2007) Silent brain infarction and platelet activation in obstructive sleep apnea. Am J Respir Crit Care Med 175:612–617

    Article  PubMed  Google Scholar 

  • O‘Leary DH, Polak JF (2002) Intima-media thickness: a tool for atherosclerosis imaging and event prediction. Am J Cardiol 90:18–21

    Article  Google Scholar 

  • O‘Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22

    Article  PubMed  CAS  Google Scholar 

  • Pasceri V, Willerson JT, Yeh ET (2000) Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102:2165–2168

    PubMed  CAS  Google Scholar 

  • Pasceri V, Cheng JS, Willerson JT, Yeh ET (2001) Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103:2531–2534

    PubMed  CAS  Google Scholar 

  • Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772

    PubMed  CAS  Google Scholar 

  • Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566–570

    PubMed  CAS  Google Scholar 

  • Silvestrini M, Rizzato B, Placidi F, Baruffaldi R, Bianconi A, Diomedi M (2002) Carotid artery wall thickness in patients with obstructive sleep apnea syndrome. Stroke 33:1782–1785

    Article  PubMed  Google Scholar 

  • Suzuki T, Nakano H, Maekawa J, Okamoto Y, Ohnishi Y, Yamauchi M, Kimura H (2004) Obstructive sleep apnea and carotid-artery intima-media thickness. Sleep 27:129–133

    PubMed  Google Scholar 

  • Schulz R, Seeger W, Fegbeutel C, Husken H, Bodeker RH, Tillmanns H, Grebe M (2005) Changes in extracranial arteries in obstructive sleep apnea. Eur Respir J 25:69–74

    Article  PubMed  CAS  Google Scholar 

  • Szmitko PE, Wang CH, Weisel RD, Jeffries GA, Anderson TJ, Verma S (2003) Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation: Part II. Circulation 108:2041–2048

    Article  PubMed  Google Scholar 

  • Saren P, Welgus HG, Kovanen PT (1996) TNF-alpha and IL-1beta selectively induce expression of 92-kDa gelatinase by human macrophages. J Immunol 157:4159–4165

    PubMed  CAS  Google Scholar 

  • Tazaki T, Minoguchi K, Yokoe T, Samson KT, Minoguchi H, Tanaka A, Watanabe Y, Adachi M (2004) Increased levels and activity of matrix metalloproteinase-9 in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 170:1354–1359

    Article  PubMed  Google Scholar 

  • Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839

    Article  PubMed  CAS  Google Scholar 

  • Wang TJ, Nam BH, Wilson PW, Wolf PA, Levy D, Polak JF, D‘Agostino RB, O‘Donnell CJ (2002) Association of C-reactive protein with carotid atherosclerosis in men and women: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 22:1662–1667

    Article  PubMed  CAS  Google Scholar 

  • Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148:209–214

    Article  PubMed  CAS  Google Scholar 

  • Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, Hirano T, Adachi M (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107:1129–1134

    Article  PubMed  CAS  Google Scholar 

  • Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V (2005) Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 353:2034–2041

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan

    Kenji Minoguchi

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  1. Kenji Minoguchi
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Editors and Affiliations

  1. Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Akira Miyazaki M.D., Ph.D. (Professor and Chairman) (Professor and Chairman)

  2. Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Michio Imawari M.D., D.M.Sc. (Professor and Chairman) (Professor and Chairman)

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© 2008 Springer

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Minoguchi, K. (2008). Sleep Apnea Syndrome and Atherosclerosis. In: Miyazaki, A., Imawari, M. (eds) New Frontiers in Lifestyle-Related Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-76428-1_12

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  • DOI: https://doi.org/10.1007/978-4-431-76428-1_12

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-76427-4

  • Online ISBN: 978-4-431-76428-1

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