Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Mechanisms of cardiac dysfunction in obstructive sleep apnea

Nature Reviews Cardiology volume 9, pages 679–688 (2012)Cite this article

Subjects

Abstract

Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality, largely as a result of myocardial anomalies. Numerous mechanisms cause OSA-related myocardial damage. The majority are initiated as a result of OSA-induced, chronic, intermittent hypoxia. The most-important mechanisms that lead to myocardial damage are increased sympathetic activity, endothelial dysfunction, systemic inflammation, oxidative stress, and metabolic anomalies. All these mechanisms promote the development of hypertension, which is common in patients with OSA. Hypertensive cardiomyopathy and coronary heart disease, as well as obesity-related, diabetic, and tachycardia-induced cardiomyopathies, are also associated with OSA. Left ventricular hypertrophy, myocardial fibrosis, atrial dilatation, and left ventricular systolic and diastolic dysfunction in patients with OSA explain the association of the disease with these clinical outcomes. The gold-standard treatment for OSA, nasal continuous positive airway pressure (CPAP), might improve cardiac symptoms and hemodynamic parameters in patients with the disease. However, large clinical trials are required to improve our understanding of the cardiac consequences of OSA, and determine the effect of treatment, particularly CPAP, on myocardial damage in symptomatic patients and primary prevention of cardiovascular disorders.

Key Points

  • Obstructive sleep apnea (OSA) causes chronic, intermittent hypoxia, which leads to an increase in sympathetic activity, endothelial dysfunction, systemic inflammation, oxidative stress, metabolic anomalies, and myocardial damage

  • Hypertension is common in patients with OSA

  • Hypertensive cardiomyopathy, coronary heart disease, and obesity-related, diabetic, and tachycardia-induced cardiomyopathies are associated with OSA

  • The main myocardial anomalies observed during OSA are left ventricular hypertrophy, myocardial fibrosis, and atrial dilatation

  • Nasal continuous positive airway pressure (CPAP) could improve cardiac symptoms and hemodynamic parameters in patients with OSA

  • Large clinical trials are needed to determine the impact of CPAP treatment on myocardial damage in patients with OSA

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cardiomyopathies related to obstructive sleep apnea.
Figure 2: Mechanisms leading to increased blood pressure in patients with obstructive sleep apnea.

Similar content being viewed by others

References

  1. Young, T., Peppard, P. E. & Gottlieb, D. J. Epidemiology of obstructive sleep apnea: a population health perspective. Am. J. Respir. Crit. Care Med. 165, 1217–1239 (2002).

    PubMed  Google Scholar 

  2. Parati, G. et al. Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (Cooperation in Scientific and Technological Research) ACTION B26 on obstructive sleep apnea. J. Hypertens. 30, 633–646 (2012).

    CAS  PubMed  Google Scholar 

  3. Iber, C., Anconi-Israel, S., Chesson, A. L. & Quan, S. F. The AASM manual for the scoring of sleep and associated events: rules, terminology, and technical specifications (American Academy of Sleep Medicine, Westchester, 2007).

    Google Scholar 

  4. Gottlieb, D. J. et al. Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study. Am. J. Respir. Crit. Care Med. 159, 502–507 (1999).

    CAS  PubMed  Google Scholar 

  5. Mazza, S. et al. Most obstructive sleep apnoea patients exhibit vigilance and attention deficits on an extended battery of tests. Eur. Respir. J. 25, 75–80 (2005).

    CAS  PubMed  Google Scholar 

  6. Leung, R. S. & Bradley, T. D. Sleep apnea and cardiovascular disease. Am. J. Respir. Crit. Care Med. 164, 2147–2165 (2001).

    CAS  PubMed  Google Scholar 

  7. Wolk, R., Kara, T. & Somers, V. K. Sleep-disordered breathing and cardiovascular disease. Circulation 108, 9–12 (2003).

    PubMed  Google Scholar 

  8. Young, T. et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch. Intern. Med. 157, 1746–1752 (1997).

    CAS  PubMed  Google Scholar 

  9. Nieto, J. et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 283, 1829–1836 (2000).

    CAS  PubMed  Google Scholar 

  10. Peppard, P. E., Young, T., Palta, M. & Skatrud, J. Prospective study of the association between sleep-disordered breathing and hypertension. N. Engl. J. Med. 342, 1378–1384 (2000).

    CAS  PubMed  Google Scholar 

  11. Baguet, J.-P. et al. Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients. J. Hypertens. 23, 521–527 (2005).

    CAS  PubMed  Google Scholar 

  12. Peker, Y., Hedner, J., Kraiczi, H. & Löth, S. Respiratory disturbance index: an independent predictor of mortality in coronary artery disease. Am. J. Respir. Crit. Care Med. 162, 81–86 (2000).

    CAS  PubMed  Google Scholar 

  13. Mooe, T., Franklin, K. A., Holmström, K., Rabben, T. & Wiklund, U. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am. J. Respir. Crit. Care Med. 164, 1910–1913 (2001).

    CAS  PubMed  Google Scholar 

  14. Milleron, O. et al. Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study. Eur. Heart J. 25, 728–734 (2004).

    PubMed  Google Scholar 

  15. Yaggi, H. K. et al. Obstructive sleep apnea as a risk factor for stroke and death. N. Engl. J. Med. 353, 2034–2041 (2005).

    CAS  PubMed  Google Scholar 

  16. Kanagala, R. et al. Sleep apnea and the recurrence of atrial fibrillation. Circulation 107, 2589–2594 (2003).

    PubMed  Google Scholar 

  17. Gami, A. S. et al. Association of atrial fibrillation and obstructive sleep apnea. Circulation 110, 364–367 (2004).

    PubMed  Google Scholar 

  18. Marin, J. M., Carrizo, S. J., Vicente, E. & Agusti, A. G. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365, 1046–1053 (2005).

    PubMed  Google Scholar 

  19. Kohler, M. & Stradling, J. R. Mechanisms of vascular damage in obstructive sleep apnea. Nat. Rev. Cardiol. 7, 677–685 (2010).

    PubMed  Google Scholar 

  20. Somers, V. K. et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. J. Am. Coll. Cardiol. 52, 686–717 (2008).

    PubMed  Google Scholar 

  21. Gottlieb, D. J. et al. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation 122, 352–360 (2010).

    PubMed  PubMed Central  Google Scholar 

  22. Leech, J. A., Onal, E. & Lopata, M. Nasal CPAP continues to improve sleep-disordered breathing and daytime oxygenation over long-term follow-up of occlusive sleep apnea syndrome. Chest 102, 1651–1655 (1992).

    CAS  PubMed  Google Scholar 

  23. Shivalkar, B. et al. Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure. J. Am. Coll. Cardiol. 47, 1433–1439 (2006).

    PubMed  Google Scholar 

  24. Dursunoglu, N. et al. Effects of CPAP on left ventricular structure and myocardial performance index in male patients with obstructive sleep apnoea. Sleep Med. 8, 51–59 (2007).

    PubMed  Google Scholar 

  25. Kohler, M. et al. CPAP and measures of cardiovascular risk in males with OSAS. Eur. Respir. J. 32, 1488–1496 (2008).

    CAS  PubMed  Google Scholar 

  26. Barbé, F. et al. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA 307, 2161–2168 (2012).

    PubMed  Google Scholar 

  27. Hsu, C. Y. et al. Sleep-disordered breathing after stroke: a randomised controlled trial of continuous positive airway pressure. J. Neurol. Neurosurg. Psychiatry 77, 1143–1149 (2006).

    PubMed  PubMed Central  Google Scholar 

  28. Craig, S. et al. Continuous positive airway pressure treatment for obstructive sleep apnoea reduces resting heart rate but does not affect dysrhythmias: a randomised controlled trial. J. Sleep Res. 18, 329–336 (2009).

    PubMed  Google Scholar 

  29. Marin, J. M. et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 307, 2169–2176 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Chobanian, A. V. 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 289, 2560–2572 (2003).

    CAS  PubMed  Google Scholar 

  31. Mancia, G. et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens. 25, 1105–1187 (2007).

    CAS  PubMed  Google Scholar 

  32. Logan, A. G. et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J. Hypertens. 19, 2271–2277 (2001).

    CAS  PubMed  Google Scholar 

  33. Baguet, J.-P. et al. Masked hypertension in obstructive sleep apnea syndrome. J. Hypertens. 26, 885–892 (2008).

    CAS  PubMed  Google Scholar 

  34. Hla, K. M. et al. Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin Sleep Cohort Study. Sleep 31, 795–800 (2008).

    PubMed  PubMed Central  Google Scholar 

  35. Grote, L., Hedner, J. & Peter, J. H. Mean blood pressure, pulse pressure and grade of hypertension in untreated hypertensive patients with sleep-related breathing disorder. J. Hypertens. 19, 683–690 (2001).

    CAS  PubMed  Google Scholar 

  36. Somers, V. K., Dyken, M. E., Clary, M. P. & Abboud, F. M. Sympathetic neural mechanisms in obstructive sleep apnea. J. Clin. Invest. 96, 1897–1904 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Greenberg, H. E., Sica, A., Batson, D. & Scharf, S. M. Chronic intermittent hypoxia increases sympathetic responsiveness to hypoxia and hypercapnia. J. Appl. Physiol. 86, 298–305 (1999).

    CAS  PubMed  Google Scholar 

  38. Brooks, D., Horner, R. L., Kozar, L. F., Render-Teixeira, C. L. & Phillipson, E. A. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J. Clin. Invest. 99, 106–109 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Dimsdale, J. E., Coy, T., Ziegler, M. G., Ancoli-Israel, S. & Clausen, J. The effect of sleep apnea on plasma and urinary catecholamines. Sleep 18, 377–381 (1995).

    CAS  PubMed  Google Scholar 

  40. Kato, M. et al. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 102, 2607–2610 (2000).

    CAS  PubMed  Google Scholar 

  41. Shamsuzzaman, A. S. et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 105, 2462–2464 (2002).

    CAS  PubMed  Google Scholar 

  42. Yokoe, T. et al. 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 (2003).

    CAS  PubMed  Google Scholar 

  43. Minoguchi, K. et al. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 172, 625–630 (2005).

    PubMed  Google Scholar 

  44. Jelic, S. et al. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation 117, 2270–2278 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

  46. 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. 165, 934–939 (2002).

    PubMed  Google Scholar 

  47. Troncoso-Brindeiro, C. M., da-Silva, A. Q., Allahdadi, K. J., Youngblood, V. & Kanagy, N. L. Reactive oxygen species contribute to sleep apnea-induced hypertension in rats. Am. J. Physiol. Heart Circ. Physiol. 293, H2971–H2976 (2007).

    PubMed  Google Scholar 

  48. Faure, P. et al. Impairment of serum albumin antioxidant properties in obstructive sleep apnoea syndrome. Eur. Respir. J. 31, 1046–1053 (2008).

    CAS  PubMed  Google Scholar 

  49. Moller, D. S., Lind, P., Strunge, B. & Pedersen, E. B. Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea. Am. J. Hypertens. 16, 274–280 (2003).

    CAS  PubMed  Google Scholar 

  50. Phillips, B. G., Kato, M., Narkiewicz, K., Choe, I. & Somers, V. K. Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea. Am. J. Physiol. Heart Circ. Physiol. 279, H234–H237 (2000).

    CAS  PubMed  Google Scholar 

  51. Drager, L. F. et al. The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome. PLoS ONE 5, e12065 (2010).

    PubMed  PubMed Central  Google Scholar 

  52. Bonsignore, M. R. et al. Metabolic syndrome, insulin resistance and sleepiness in real-life obstructive sleep apnoea. Eur. Respir. J. 39, 1136–1143 (2012).

    CAS  PubMed  Google Scholar 

  53. Kanagy, N. L., Walker, B. R. & Nelin, L. D. Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension 37, 511–515 (2001).

    CAS  PubMed  Google Scholar 

  54. Ryan, S., Ward, S., Heneghan, C. & McNicholas, W. T. Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome. Chest 131, 1100–1107 (2007).

    PubMed  Google Scholar 

  55. Durán-Cantolla, J. et al. Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial. BMJ 341, c5991 (2010).

    PubMed  Google Scholar 

  56. Bazzano, L. A., Khan, Z., Reynolds, K. & He, J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 50, 417–423 (2007).

    CAS  PubMed  Google Scholar 

  57. Haentjens, P. et al. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome. Arch. Intern. Med. 167, 757–765 (2007).

    PubMed  Google Scholar 

  58. Hedner, J., Darpö, B., Ejnell, H., Carlson, J. & Caidahl, K. Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications. Eur. Respir. J. 8, 222–229 (1995).

    CAS  PubMed  Google Scholar 

  59. Imadojemu, V. A. et al. Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy. Am. J. Respir. Crit. Care Med. 165, 950–953 (2002).

    PubMed  Google Scholar 

  60. Kraiczi, H., Hedner, J., Peker, Y. & Grote, L. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 161, 1423–1428 (2000).

    CAS  PubMed  Google Scholar 

  61. Pépin, J.-L. et al. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am. J. Respir. Crit. Care Med. 182, 954–960 (2010).

    PubMed  Google Scholar 

  62. Haider, A. W., Larson, M. G., Franklin, S. S. & Levy, D. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study. Ann. Intern. Med. 138, 10–16 (2003).

    PubMed  Google Scholar 

  63. Schillaci, G. et al. Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension. Hypertension 35, 580–586 (2000).

    CAS  PubMed  Google Scholar 

  64. Verdecchia, P. et al. Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 81, 528–536 (1990).

    CAS  PubMed  Google Scholar 

  65. Hedner, J., Ejnell, H. & Caidahl, K. Left ventricular hypertrophy independent of hypertension in patients with obstructive sleep apnoea. J. Hypertens. 8, 941–946 (1990).

    CAS  PubMed  Google Scholar 

  66. Kraiczi, H., Peker, Y., Caidahl, K., Samuelsson, A. & Hedner, J. Blood pressure, cardiac structure and severity of obstructive sleep apnea in a sleep clinic population. J. Hypertens. 19, 2071–2078 (2001).

    CAS  PubMed  Google Scholar 

  67. Chami, H. A. et al. Left ventricular morphology and systolic function in sleep-disordered breathing: the Sleep Heart Health Study. Circulation 117, 2599–2607 (2008).

    PubMed  PubMed Central  Google Scholar 

  68. Noda, A., Okada, T., Yasuma, F., Nakashima, N. & Yokota, M. Cardiac hypertrophy in obstructive sleep apnea syndrome. Chest 107, 1538–1544 (1995).

    CAS  PubMed  Google Scholar 

  69. Baguet, J.-P. et al. Left ventricular diastolic dysfunction is linked to severity of obstructive sleep apnoea. Eur. Respir. J. 36, 1323–1329 (2010).

    PubMed  Google Scholar 

  70. Kraiczi, H., Caidahl, K., Samuelsson, A., Peker, Y. & Hedner, J. Impairment of vascular endothelial function and left ventricular filling. Association with the severity of apnea-induced hypoxemia during sleep. Chest 119, 1085–1091 (2001).

    CAS  PubMed  Google Scholar 

  71. Dursunoglu, D. et al. Impact of obstructive sleep apnea on left ventricular mass and global function. Eur. Respir. J. 26, 283–288 (2005).

    CAS  PubMed  Google Scholar 

  72. Chen, L. et al. Left ventricular dysfunction and associated cellular injury in rats exposed to chronic intermittent hypoxia. J. Appl. Physiol. 104, 218–223 (2008).

    CAS  PubMed  Google Scholar 

  73. Hayashi, T. et al. Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress. Am. J. Physiol. Heart Circ. Physiol. 294, H2197–H2203 (2008).

    CAS  PubMed  Google Scholar 

  74. López, B. et al. Biochemical assessment of myocardial fibrosis in hypertensive heart disease. Hypertension 38, 1222–1226 (2001).

    PubMed  Google Scholar 

  75. Marney, A. M. & Brown, N. J. Aldosterone and end-organ damage. Clin. Sci. (Lond.) 113, 267–278 (2007).

    CAS  Google Scholar 

  76. Pratt-Ubunama, M. N. et al. Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest 131, 453–459 (2007).

    CAS  PubMed  Google Scholar 

  77. Vautrin, E. et al. Procollagen type III amino terminal peptide (PIIIP) is associated with left ventricular diastolic dysfunction in obstructive sleep apnoea. Int. J. Cardiol. 151, 387–388 (2011).

    PubMed  Google Scholar 

  78. Levin, E. R., Gardner, D. G. & Samson, W. K. Natriuretic peptides. N. Engl. J. Med. 339, 321–328 (1998).

    CAS  PubMed  Google Scholar 

  79. Svatikova, A. et al. Plasma brain natriuretic peptide in obstructive sleep apnea. Am. J. Cardiol. 94, 529–532 (2004).

    CAS  PubMed  Google Scholar 

  80. Patwardhan, A. A. et al. Obstructive sleep apnea and plasma natriuretic peptide levels in a community-based sample. Sleep 29, 1301–1306 (2006).

    PubMed  Google Scholar 

  81. Usui, Y. et al. Plasma B-type natriuretic peptide level is associated with left ventricular hypertrophy among obstructive sleep apnoea patients. J. Hypertens. 26, 117–123 (2008).

    CAS  PubMed  Google Scholar 

  82. Cifçi, N., Uyar, M., Elbek, O., Süyür, H. & Ekinci, E. Impact of CPAP treatment on cardiac biomarkers and pro-BNP in obstructive sleep apnea syndrome. Sleep Breath. 14, 241–244 (2010).

    PubMed  Google Scholar 

  83. Colish, J. et al. Obstructive sleep apnea: effects of continuous positive airway pressure on cardiac remodeling as assessed by cardiac biomarkers, echocardiography, and cardiac MRI. Chest 141, 674–681 (2012).

    PubMed  Google Scholar 

  84. Peker, Y., Carlson, J. & Hedner, J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur. Respir. J. 28, 596–602 (2006).

    CAS  PubMed  Google Scholar 

  85. Nakashima, H. et al. Obstructive sleep apnoea inhibits the recovery of left ventricular function in patients with acute myocardial infarction. Eur. Heart J. 27, 2317–2322 (2006).

    PubMed  Google Scholar 

  86. Arnaud, C. et al. The inflammatory preatherosclerotic remodeling induced by intermittent hypoxia is attenuated by RANTES/CCL5 inhibition. Am. J. Respir. Crit. Care Med. 184, 724–731 (2011).

    CAS  PubMed  Google Scholar 

  87. Dematteis, M. et al. Intermittent hypoxia induces early functional cardiovascular remodeling in mice. Am. J. Respir. Crit. Care Med. 177, 227–235 (2008).

    PubMed  Google Scholar 

  88. Tzima, E. et al. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437, 426–431 (2005).

    CAS  PubMed  Google Scholar 

  89. Oga, T. et al. Effects of obstructive sleep apnea with intermittent hypoxia on platelet aggregability. J. Atheroscler. Thromb. 16, 862–869 (2009).

    PubMed  Google Scholar 

  90. Terada, S. et al. Abnormal coagulation and platelet profile in patients with obstructive sleep apnea syndrome. Int. J. Cardiol. 146, 423–425 (2011).

    PubMed  Google Scholar 

  91. Monneret, D. et al. Association of urinary 15-F2t-isoprostane level with oxygen desaturation and carotid intima-media thickness in nonobese sleep apnea patients. Free Radic. Biol. Med. 48, 619–625 (2010).

    CAS  PubMed  Google Scholar 

  92. Savransky, V. et al. Chronic intermittent hypoxia induces atherosclerosis. Am. J. Respir. Crit. Care Med. 175, 1290–1297 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Baguet, J.-P. et al. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest 128, 3407–3412 (2005).

    PubMed  Google Scholar 

  94. Ip, M. S., Tse, H. F., Lam, B., Tsang, K. W. & Lam, W. K. Endothelial function in obstructive sleep apnea and response to treatment. Am. J. Respir. Crit. Care Med. 169, 348–353 (2004).

    PubMed  Google Scholar 

  95. Itzhaki, S., Lavie, L., Pillar, G., Tal, G. & Lavie, P. Endothelial dysfunction in obstructive sleep apnea measured by peripheral arterial tone response in the finger to reactive hyperemia. Sleep 28, 594–600 (2005).

    PubMed  Google Scholar 

  96. Butt, M. et al. Myocardial perfusion by myocardial contrast echocardiography and endothelial dysfunction in obstructive sleep apnea. Hypertension 58, 417–424 (2011).

    CAS  PubMed  Google Scholar 

  97. Ciccone, M. M. et al. Reversibility of the endothelial dysfunction after CPAP therapy in OSAS patients. Int. J. Cardiol. 158, 383–386 (2012).

    PubMed  Google Scholar 

  98. Levy, D., Garrison, R. J., Savage, D. D., Kannel, W. B. & Castelli, W. P. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N. Engl. J. Med. 322, 1561–1566 (1990).

    CAS  PubMed  Google Scholar 

  99. Antony, I., Nitenberg, A., Foult, J. M. & Aptecar, E. Coronary vasodilator reserve in untreated and treated hypertensive patients with and without left ventricular hypertrophy. J. Am. Coll. Cardiol. 22, 514–520 (1993).

    CAS  PubMed  Google Scholar 

  100. Lembo, G. et al. Systemic hypertension and coronary artery disease: the link. Am. J. Cardiol. 82, 2H–7H (1998).

    CAS  PubMed  Google Scholar 

  101. Vgontzas, A. N. et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J. Clin. Endocrinol. Metab. 85, 1151–1158 (2000).

    CAS  PubMed  Google Scholar 

  102. Hou, N. et al. Leptin induces hypertrophy through activating the peroxisome proliferator-activated receptor α pathway in cultured neonatal rat cardiomyocytes. Clin. Exp. Pharmacol. Physiol. 37, 1087–1095 (2010).

    CAS  PubMed  Google Scholar 

  103. Devereux, R. B. & Roman, M. J. in Hypertension: pathophysiology, diagnosis and management. Hypertensive cardiac hypertrophy: pathophysiologic and clinical characteristics (eds Laragh, J. H. & Brenner, B. M.) 409–432 (Raven Press Ltd, New York, 1995).

    Google Scholar 

  104. Schwartzkopff, B. et al. Structural and functional alterations of the intramyocardial coronary arterioles in patients with arterial hypertension. Circulation 88, 993–1003 (1993).

    CAS  PubMed  Google Scholar 

  105. Belaidi, E. et al. Role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea. J. Am. Coll. Cardiol. 53, 1309–1317 (2009).

    CAS  PubMed  Google Scholar 

  106. Park, A. M. & Suzuki, Y. J. Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice. J. Appl. Physiol. 102, 1806–1814 (2007).

    CAS  PubMed  Google Scholar 

  107. Park, A. M., Nagase, H., Kumar, S. V. & Suzuki, Y. J. Effects of intermittent hypoxia on the heart. Antioxid. Redox Signal. 9, 723–729 (2007).

    CAS  PubMed  Google Scholar 

  108. Joyeux-Faure, M. et al. Chronic intermittent hypoxia increases infarction in the isolated rat heart. J. Appl. Physiol. 98, 1691–1696 (2005).

    CAS  PubMed  Google Scholar 

  109. Ramond, A. et al. Oxidative stress mediates cardiac infarction aggravation induced by intermittent hypoxia. Fundam. Clin. Pharmacol. http://dx.doi.org/10.1111/j.1472-8206.2011.01015.x.

  110. Young, T., Peppard, P. E. & Taheri, S. Excess weight and sleep-disordered breathing. J. Appl. Physiol. 99, 1592–1599 (2005).

    PubMed  Google Scholar 

  111. Coughlin, S. R., Mawdsley, L., Mugarza, J. A., Calverley, P. M. & Wilding, J. P. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur. Heart J. 25, 735–741 (2004).

    PubMed  Google Scholar 

  112. Lee, S. D. et al. The coexistence of nocturnal sustained hypoxia and obesity additively increases cardiac apoptosis. J. Appl. Physiol. 104, 1144–1153 (2008).

    CAS  PubMed  Google Scholar 

  113. Dela-Cruz, C. S. & Matthay, R. A. Role of obesity in cardiomyopathy and pulmonary hypertension. Clin. Chest Med. 30, 509–523 (2009).

    PubMed  Google Scholar 

  114. Alpert, M. A. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am. J. Med. Sci. 321, 225–236 (2001).

    CAS  PubMed  Google Scholar 

  115. Leopoldo, A. S. et al. Involvement of L-type calcium channel and SERCA2a in myocardial dysfunction induced by obesity. J. Cell. Physiol. 226, 2934–2942 (2011).

    CAS  PubMed  Google Scholar 

  116. Foster, G. D. et al. Sleep AHEAD Research Group. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care 32, 1017–1019 (2009).

    PubMed  PubMed Central  Google Scholar 

  117. Borel, A. L. et al. High prevalence of obstructive sleep apnoea syndrome in a type 1 diabetic adult population: a pilot study. Diabet. Med. 27, 1328–1329 (2010).

    PubMed  Google Scholar 

  118. Tahrani, A. A. et al. Obstructive sleep apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes. Am. J. Respir. Crit. Care Med. 186, 434–441 (2012).

    PubMed  PubMed Central  Google Scholar 

  119. Poornima, I. G., Parikh, P. & Shannon, R. P. Diabetic cardiomyopathy: the search for a unifying hypothesis. Circ. Res. 98, 596–605 (2006).

    CAS  PubMed  Google Scholar 

  120. Mizushige, K. et al. Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation 101, 899–907 (2000).

    CAS  PubMed  Google Scholar 

  121. Ilercil, A. et al. Associations of insulin levels with left ventricular structure and function in American Indians: the strong heart study. Diabetes 51, 1543–1547 (2002).

    CAS  PubMed  Google Scholar 

  122. Iacobellis, G. et al. Relationship of insulin sensitivity and left ventricular mass in uncomplicated obesity. Obes. Res. 11, 518–524 (2003).

    PubMed  Google Scholar 

  123. Du, X. et al. Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J. Clin. Invest. 112, 1049–1057 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Sowers, J. R., Epstein, M. & Frohlich, E. D. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension 37, 1053–1059 (2001).

    CAS  PubMed  Google Scholar 

  125. Drager, L. F., Bortolotto, L. A., Pedrosa, R. P., Krieger, E. M. & Lorenzi-Filho, G. Left atrial diameter is independently associated with arterial stiffness in patients with obstructive sleep apnea: potential implications for atrial fibrillation. Int. J. Cardiol. 144, 257–259 (2010).

    PubMed  Google Scholar 

  126. Shinbane, J. S. et al. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J. Am. Coll. Cardiol. 29, 709–715 (1997).

    CAS  PubMed  Google Scholar 

  127. Burchell, S. A., Spinale, F. G., Crawford, F. A., Tanaka, R. & Zile, M. R. Effects of chronic tachycardia-induced cardiomyopathy on the β-adrenergic receptor system. J. Thorac. Cardiovasc. Surg. 104, 1006–1012 (1992).

    CAS  PubMed  Google Scholar 

  128. Spinale, F. G. et al. Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia. Am. J. Physiol. 261, H308–H318 (1991).

    CAS  PubMed  Google Scholar 

  129. Sin, D. D. et al. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am. J. Respir. Crit. Care Med. 160, 1101–1106 (1999).

    CAS  PubMed  Google Scholar 

  130. Shahar, E. et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am. J. Respir. Crit. Care Med. 163, 19–25 (2001).

    CAS  PubMed  Google Scholar 

  131. Hogg, K., Swedberg, K. & McMurray, J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J. Am. Coll. Cardiol. 43, 317–327 (2004).

    PubMed  Google Scholar 

  132. Arias, M. A. et al. Obstructive sleep apnea syndrome affects left ventricular diastolic function. Effects of nasal continuous positive airway pressure. Circulation 112, 375–383 (2005).

    PubMed  Google Scholar 

  133. Niroumand, M., Kuperstein, R., Sasson, Z. & Hanly, P. J. Impact of obstructive sleep apnea on left ventricular mass and diastolic function. Am. J. Respir. Crit. Care Med. 163, 1632–1636 (2001).

    CAS  PubMed  Google Scholar 

  134. Bradley, T. D., Hall, M. J., Ando, S. & Floras, J. S. Hemodynamic effects of simulated obstructive apneas in humans with and without heart failure. Chest 119, 1827–1835 (2001).

    CAS  PubMed  Google Scholar 

  135. Lorell, B. H. & Carabello, B. A. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 102, 470–479 (2000).

    CAS  PubMed  Google Scholar 

  136. Virolainen, J., Ventilä, M., Turto, H. & Kupari, M. Effect of negative intrathoracic pressure on left ventricular pressure dynamics and relaxation. J. Appl. Physiol. 79, 455–460 (1995).

    CAS  PubMed  Google Scholar 

  137. Tavil, Y. et al. Comparison of right ventricular functions by tissue doppler imaging in patients with obstructive sleep apnea syndrome with or without hypertension. Int. J. Cardiovasc. Imaging 23, 469–477 (2007).

    PubMed  Google Scholar 

  138. Brinker, J. A. et al. Leftward septal displacement during right ventricular loading in man. Circulation 61, 626–633 (1980).

    CAS  PubMed  Google Scholar 

  139. Drager, L. F. et al. Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodelling. Chest 131, 1379–1386 (2007).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Grenoble University Hospital, BP 217, Grenoble, 38043, France

    Jean-Philippe Baguet & Gilles Barone-Rochette

  2. HP2 Laboratory (Hypoxia: Pathophysiology), INSERM U1042, Joseph Fourier University, Grenoble Cedex 9, 38043, France

    Renaud Tamisier, Patrick Levy & Jean-Louis Pépin

Authors
  1. Jean-Philippe Baguet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gilles Barone-Rochette
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renaud Tamisier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrick Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Louis Pépin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.-P. Baguet researched data for the article, provided a substantial contribution to discussions of the content, and wrote the article. G. Barone-Rochette researched data for the article. R. Tamisier and P. Levy provided a substantial contribution to discussions of the content. J.-L. Pépin provided a substantial contribution to discussions of the content and wrote the article. All the authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Jean-Philippe Baguet.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baguet, JP., Barone-Rochette, G., Tamisier, R. et al. Mechanisms of cardiac dysfunction in obstructive sleep apnea. Nat Rev Cardiol 9, 679–688 (2012). https://doi.org/10.1038/nrcardio.2012.141

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2012.141

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing