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睡眠時無呼吸と心血管疾患

非常に多くの研究が睡眠時無呼吸と心血管疾患の関係に着目してきました。 それらの研究の結果、主に以下がわかりました。

  • 低酸素症の原因となり、無呼吸時の呼吸努力により胸腔内圧変動を増大させ、交感神経系を活性化させて、心血管系に様々なダメージを引き起こします。1-4
  • リスク要因に関わりなく、高血圧症との強い関連が指摘されています。5-8
  • 30%を超える高血圧症の患者さんに見られます。9
  • 薬剤抵抗性の高血圧症の患者さんの80%に見られます。10
  • CPAP療法により血圧が臨床上有意に低下することがあります。 この低下により冠動脈性心疾患イベントのリスクが37%、脳梗塞のリスクが56%低減されます。11,12,13
  • 患者さんは他の既知のリスク要因に関わりなく、心不全のリスクが2.4倍増加します。14
  • 心不全を併発している患者さんにCPAP療法を実施した場合、左室機能が改善されます。15
  • 心血管疾患の患者さんによく見られ、心房細動のある方の50%に見られます。16
  • アテローム発生に関連する炎症・酸化・血管内皮作用各マーカーの上昇が見られます。 これらのマーカーはCPAP療法による睡眠時無呼吸の治療により改善されます。17-20
  • 重症の場合、心血管疾患イベントのリスクを有意に増大させます。 このリスクはCPAP療法による治療により低減します。21,22

心不全は患者さんの睡眠を寸断し生存率を低下させるチェーン・ストークス呼吸 (CSR) を伴う例が多く見られます。

参考資料

  1. Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease.  JAMA 2003;290:1906-14.
  2. Lattimore JD, Celermajer DS, Wilcox I.  Obstructive sleep apnea and cardiovascular disease.  J Am Coll Cardiol 2003;41:1429-37.
  3. Bradley TD, Floras JS. Sleep apnea and heart failure: Part I: obstructive sleep apnea.  Circulation 2003;107:1671-8.
  4. Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J.   Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up.  Am J Respir Crit Care Med 2002;166:159-165.
  5. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension.  N Engl J Med 2000;342:1378-1384.
  6. Lavie P, Herer P, Hoffstein V.  Obstructive sleep apnea syndrome as a risk factor for hypertension: population study.  BMJ 2000;320:479-82.
  7. Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, D'Agostino RB, Newman AB, Lebowitz MD, Pickering TG. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study.  JAMA 2000;283:1829-1836.
  8. Bixler EO, Vgontzas AN, Lin HM, Ten Have T, Leiby BE, Vela-Bueno A, Kales A. Association of hypertension and sleep-disordered breathing.  Arch Intern Med 2000;160:2289-95.  
  9. Sjostrom C, Lindberg E, Elmasry A, Hagg A, Svardsudd K, Janson C. Prevalence of sleep apnoea and snoring in hypertensive men: a population based study.  Thorax 2002;57:602-7.
  10. 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 J Hypertens 2001;19:2271-7.
  11. Logan AG, Tkacova R, Perlikowski SM, Leung RS, Tisler A, Floras JS, Bradley TD. Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.  Eur Respir J 2003;21:241-7.
  12. Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH.  Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea.  Circulation 2003;107:68-73.
  13. Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, Davies RJ.  Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial.  Lancet 2002;359:204-10.
  14. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, O'Connor GT, Boland LL, Schwartz JE, Samet JM. 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.
  15. Kaneko Y, Floras JS, Usui K, Plante J, Tkacova R, Kubo T, Ando S, Bradley TD. Cardiovascular effects of continuous positive airway pressure in patients with heart hailure and obstructive sleep apnea.  N Engl J Med 2003;348:1233-1241.
  16. Lanfranchi PA, Braghiroli A, Bosimini E, Mazzuero G, Colombo R, Donner CF, Giannuzzi P.  Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure.  Circulation 1999;99:1435-40.
  17. Teschler H, Dohring J, Wang YM, Berthon-Jones M.  Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure.  Am J Respir Crit Care Med 2001;164:614-9.
  18. Pepperell JC, Maskell NA, Jones DR, Langford-Wiley BA, Crosthwaite N, Stradling JR, Davies RJ. A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure.  J Respir Crit Care Med 2003;168:1109-14.
  19. Topfer V, El-Sebai M, Wessendorf TE, Moraidis I, Teschler H.[   Adaptive servoventilation: effect on Cheyne-Stokes-Respiration and on quality of life  ]Pneumologie 2004;58:28-32.
  20. Schadlich S, Konigs I, Kalbitz F, Blankenburg T, Busse HJ, Schutte W.[ Cardiac efficiency in patients with Cheyne-Stokes respiration as a result of heart insufficiency during long-term nasal respiratory treatment with adaptive servo ventilation (AutoSet CS)  ]Z Kardiol 2004;93:454-62.
  21. Philippe C; Stoica-Herman M; Drouot X; Raffestin B; Escourrou P; Hittinger L; Michel P-L; Rouault S; d'Ortho M-P. Compliance with and effectiveness of adaptive servoventilation versus continuous positive airway pressure in the treatment of Cheyne-Stokes respiration in heart failure over a six month period.  Heart 2006;92(3):337-42.
  22. Gami AS, Pressman G, Caples SM, Kanagala R, Gard JJ, Davison DE, Malouf J, Ammash N, Friedman P, Somers VK. Association of atrial fibrillation and obstructive sleep apnea.  Circulation 2004;110(4):364-7.
  23. Ip MS, Tse HF, Lam B, Tsang KW, Lam WK. Endothelial function in obstructive sleep apnea and response to treatment.  Am J Respir Crit Care Med 2004;169:348-53.
  24. Ip MSM, Lam B, Chan LY, Zheng L, Tsang KWT, Fung PCW, Lam WK.  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.
  25. Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, Somers VK.  Elevated C-reactive protein in patients with obstructive sleep apnea.  Circulation 2002;105:2462-4.
  26. 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;165:934-9.
  27. Marin JM, Carrizo SJ, Vicente E, Agusti AG.  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(9464):1046-53.
  28. Doherty LS, Kiely JL, Swan V, McNicholas WT.  Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome.  Chest 2005;127(6):2076-84.