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Sleep and Breathing

, Volume 21, Issue 1, pp 181–189 | Cite as

Meta-analysis of all-cause and cardiovascular mortality in obstructive sleep apnea with or without continuous positive airway pressure treatment

  • Yiqun Fu
  • Yunyan Xia
  • Hongliang Yi
  • Huajun XuEmail author
  • Jian GuanEmail author
  • Shankai Yin
ENT • Original Article

Abstract

Purpose

The associations between obstructive sleep apnea (OSA) and all-cause and cardiovascular mortality are well established but are not entirely consistent. To accurately evaluate these associations as well as the therapeutic effects of continuous positive airway pressure (CPAP), we conducted a comprehensive meta-analysis of all eligible cohort studies.

Methods

Electronic literature databases (i.e., PubMed and Embase) were searched for relevant studies published before January 2016 that evaluated the associations between OSA and all-cause or cardiovascular mortality. Random-effect models were used to calculate the pooled hazard ratio (HR) and corresponding 95 % confidence intervals (CIs) for categorical risk estimates. The therapeutic effects of CPAP treatment for all-cause and cardiovascular mortality in OSA were examined through the meta-analysis.

Results

The 27 cohort studies included in the meta-analysis included 3,162,083 participants. Compared to the control group, the pooled HR of all-cause mortality was 1.19 (95 % CI, 0.86–1.65) for mild OSA, 1.28 (0.96–1.69) for moderate OSA, and 2.13 (1.68–2.68) for severe OSA. The pooled HR of cardiovascular mortality was 1.24 (0.53–2.55) for mild OSA, 2.05 (0.57–5.47) for moderate OSA, and 2.73 (1.94–3.85) for severe OSA. All-cause mortality (HR 0.66; 0.59–0.73) and cardiovascular mortality (HR 0.37; 0.16–0.54) were significantly lower in CPAP-treated than in untreated patients. There were no differences in cardiovascular mortality in CPAP-treated OSA patients vs. normal control subjects (HR 0.82; 0.52–1.29).

Conclusions

Greater attention should be paid to severe OSA, as it is an independent predictor for risk for all-cause and cardiovascular mortality. CPAP is an effective treatment that reduces risk of mortality.

Keywords

Obstructive sleep apnea All-cause mortality Cardiovascular mortality Meta-analysis 

Notes

Compliance with ethical standards

Funding

This study was supported by grants-in-aid from multi-center clinical research project from school of medicine, Shanghai Jiao Tong University (DLY201502), and Shanghai Shen-Kang Hospital Management Center Project of Shanghai (SHDC12015101).

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

Ethical approval was not necessary for this meta-analysis, as only identified pooled data from previously approved individual studies were used.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11325_2016_1393_MOESM1_ESM.pdf (947 kb)
ESM 1 (PDF 947 kb)

References

  1. 1.
    Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T (2008) 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 in collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 118(10):1080–1111. doi: 10.1161/circulationaha.107.189420 CrossRefPubMedGoogle Scholar
  2. 2.
    Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328(17):1230–1235. doi: 10.1056/NEJM199304293281704 CrossRefPubMedGoogle Scholar
  3. 3.
    Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177(9):1006–1014. doi: 10.1093/aje/kws342 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pan L, Xie X, Liu D, Ren D, Guo Y (2016) Obstructive sleep apnoea and risks of all-cause mortality: preliminary evidence from prospective cohort studies. Sleep & breathing = Schlaf & Atmung 20(1):345–353. doi: 10.1007/s11325-015-1295-7 CrossRefGoogle Scholar
  5. 5.
    Ge X, Han F, Huang Y, Zhang Y, Yang T, Bai C, Guo X (2013) Is obstructive sleep apnea associated with cardiovascular and all-cause mortality? PLoS One 8(7):e69432. doi: 10.1371/journal.pone.0069432 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wang X, Ouyang Y, Wang Z, Zhao G, Liu L, Bi Y (2013) Obstructive sleep apnea and risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Int J Cardiol 169(3):207–214. doi: 10.1016/j.ijcard.2013.08.088 CrossRefPubMedGoogle Scholar
  7. 7.
    Gooneratne NS, Richards KC, Joffe M, Lam RW, Pack F, Staley B, Dinges DF, Pack AI (2011) Sleep disordered breathing with excessive daytime sleepiness is a risk factor for mortality in older adults. Sleep 34(4):435–442PubMedPubMedCentralGoogle Scholar
  8. 8.
    Yeboah J, Redline S, Johnson C, Tracy R, Ouyang P, Blumenthal RS, Burke GL, Herrington DM (2011) Association between sleep apnea, snoring, incident cardiovascular events and all-cause mortality in an adult population: MESA. Atherosclerosis 219(2):963–968. doi: 10.1016/j.atherosclerosis.2011.08.021 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Xu H, Yi H, Guan J, Yin S (2014) Effect of continuous positive airway pressure on lipid profile in patients with obstructive sleep apnea syndrome: a meta-analysis of randomized controlled trials. Atherosclerosis 234(2):446–453. doi: 10.1016/j.atherosclerosis.2014.03.034 CrossRefPubMedGoogle Scholar
  10. 10.
    Xu H, Wang Y, Guan J, Yi H, Yin S (2015) Effect of CPAP on endothelial function in subjects with obstructive sleep apnea: a meta-analysis. Respir Care 60(5):749–755. doi: 10.4187/respcare.03739 CrossRefPubMedGoogle Scholar
  11. 11.
    Bazzano LA, Khan Z, Reynolds K, He J (2007) Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 50(2):417–423. doi: 10.1161/HYPERTENSIONAHA.106.085175 CrossRefPubMedGoogle Scholar
  12. 12.
    Montesi SB, Edwards BA, Malhotra A, Bakker JP (2012) The effect of continuous positive airway pressure treatment on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med 8(5):587–596. doi: 10.5664/jcsm.2170 PubMedPubMedCentralGoogle Scholar
  13. 13.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010 8(5):336–341. doi: 10.1016/j.ijsu.2010.02.007 Google Scholar
  14. 14.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi: 10.1136/bmj.327.7414.557 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRefPubMedGoogle Scholar
  16. 16.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    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(19):2034–2041. doi: 10.1056/NEJMoa043104 CrossRefPubMedGoogle Scholar
  18. 18.
    Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, Stubbs R, Hla KM (2008) Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 31(8):1071–1078PubMedPubMedCentralGoogle Scholar
  19. 19.
    Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O’Connor GT, Rapoport DM, Redline S, Resnick HE, Robbins JA, Shahar E, Unruh ML, Samet JM (2009) Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 6(8):e1000132. doi: 10.1371/journal.pmed.1000132 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Shah NA, Yaggi HK, Concato J, Mohsenin V (2010) Obstructive sleep apnea as a risk factor for coronary events or cardiovascular death. Sleep & breathing = Schlaf & Atmung 14(2):131–136. doi: 10.1007/s11325-009-0298-7 CrossRefGoogle Scholar
  21. 21.
    Anandam A, Patil M, Akinnusi M, Jaoude P, El-Solh AA (2013) Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: an observational study. Respirology 18(8):1184–1190. doi: 10.1111/resp.12140 CrossRefPubMedGoogle Scholar
  22. 22.
    Gami AS, Olson EJ, Shen WK, Wright RS, Ballman KV, Hodge DO, Herges RM, Howard DE, Somers VK (2013) Obstructive sleep apnea and the risk of sudden cardiac death: a longitudinal study of 10,701 adults. J Am Coll Cardiol 62(7):610–616. doi: 10.1016/j.jacc.2013.04.080 CrossRefPubMedGoogle Scholar
  23. 23.
    Kendzerska T, Gershon AS, Hawker G, Leung RS, Tomlinson G (2014) Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: a decade-long historical cohort study. PLoS Med 11(2):e1001599. doi: 10.1371/journal.pmed.1001599 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Molnar MZ, Mucsi I, Novak M, Szabo Z, Freire AX, Huch KM, Arah OA, Ma JZ, Lu JL, Sim JJ, Streja E, Kalantar-Zadeh K, Kovesdy CP (2015) Association of incident obstructive sleep apnoea with outcomes in a large cohort of US veterans. Thorax 70(9):888–895. doi: 10.1136/thoraxjnl-2015-206970 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Marin JM, Carrizo SJ, Vicente E, Agusti AGN (2005) 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(9464):1046–1053. doi: 10.1016/s0140-6736(05)74229-x CrossRefPubMedGoogle Scholar
  26. 26.
    Doherty LS, Kiely JL, Swan V, McNicholas WT (2005) Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest 127(6):2076–2084. doi: 10.1378/chest.127.6.2076 CrossRefPubMedGoogle Scholar
  27. 27.
    Munoz R, Duran-Cantolla J, Martinez-Vila E, Gallego J, Rubio R, Aizpuru F, De La Torre G (2006) Severe sleep apnea and risk of ischemic stroke in the elderly. Stroke; a journal of cerebral circulation 37(9):2317–2321. doi: 10.1161/01.STR.0000236560.15735.0f CrossRefGoogle Scholar
  28. 28.
    Hader C, Hinz M, Welz-Barth A, Rasche K (2006) Sleep disordered breathing in the elderly: a three year longitudinal cohort study. J Physiol Pharmacol 57(Supp 4):119–129PubMedGoogle Scholar
  29. 29.
    Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J (2002) Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med 166(2):159–165. doi: 10.1164/rccm.2105124 CrossRefPubMedGoogle Scholar
  30. 30.
    Peker Y, Carlson J, Hedner J (2006) Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. The European respiratory journal 28(3):596–602. doi: 10.1183/09031936.06.00107805 CrossRefPubMedGoogle Scholar
  31. 31.
    Buchner NJ, Sanner BM, Borgel J, Rump LC (2007) Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. Am J Respir Crit Care Med 176(12):1274–1280. doi: 10.1164/rccm.200611-1588OC CrossRefPubMedGoogle Scholar
  32. 32.
    Johansson P, Alehagen U, Ulander M, Svanborg E, Dahlstrom U, Brostrom A (2011) Sleep disordered breathing in community dwelling elderly: associations with cardiovascular disease, impaired systolic function, and mortality after a six-year follow-up. Sleep Med 12(8):748–753. doi: 10.1016/j.sleep.2011.03.012 CrossRefPubMedGoogle Scholar
  33. 33.
    Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM (2012) Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study. Ann Intern Med 156(2):115–122. doi: 10.7326/0003-4819-156-2-201201170-00006 CrossRefPubMedGoogle Scholar
  34. 34.
    Martinez-Garcia MA, Campos-Rodriguez F, Catalan-Serra P, Soler-Cataluna JJ, Almeida-Gonzalez C, De la Cruz MI, Duran-Cantolla J, Montserrat JM (2012) Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long-term continuous positive airway pressure treatment: a prospective observational study. Am J Respir Crit Care Med 186(9):909–916. doi: 10.1164/rccm.201203-0448OC CrossRefPubMedGoogle Scholar
  35. 35.
    Muraja-Murro A, Eskola K, Kolari T, Tiihonen P, Hukkanen T, Tuomilehto H, Peltonen M, Mervaala E, Toyras J (2013) Mortality in middle-aged men with obstructive sleep apnea in Finland. Sleep & breathing = Schlaf & Atmung 17(3):1047–1053. doi: 10.1007/s11325-012-0798-8 CrossRefGoogle Scholar
  36. 36.
    Marrone O, Lo Bue A, Salvaggio A, Dardanoni G, Insalaco G (2013) Comorbidities and survival in obstructive sleep apnoea beyond the age of 50. Eur J Clin Investig 43(1):27–33. doi: 10.1111/eci.12011 CrossRefGoogle Scholar
  37. 37.
    Jennum P, Tonnesen P, Ibsen R, Kjellberg J (2015) All-cause mortality from obstructive sleep apnea in male and female patients with and without continuous positive airway pressure treatment: a registry study with 10 years of follow-up. Nat Sci Sleep 7:43–50. doi: 10.2147/NSS.S75166 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Yuan X, Fang J, Wang L, Yao L, Li L, Zhan X, Wu H, Pinto JM, Wei Y (2015) Adequate continuous positive airway pressure therapy reduces mortality in Chinese patients with obstructive sleep apnea. Sleep & breathing = Schlaf & Atmung 19(3):911–920. doi: 10.1007/s11325-014-1091-9 CrossRefGoogle Scholar
  39. 39.
    Ou Q, Chen YC, Zhuo SQ, Tian XT, He CH, Lu XL, Gao XL (2015) Continuous positive airway pressure treatment reduces mortality in elderly patients with moderate to severe obstructive severe sleep apnea: a cohort study. PLoS One 10(6):e0127775. doi: 10.1371/journal.pone.0127775 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Lavie P, Lavie L, Herer P (2005) All-cause mortality in males with sleep apnoea syndrome: declining mortality rates with age. The European respiratory journal 25(3):514–520. doi: 10.1183/09031936.05.00051504 CrossRefPubMedGoogle Scholar
  41. 41.
    Morimoto S, Takahashi T, Okaishi K, Okuro M, Nakahashi T, Sakamoto D, Mizuno T, Kanda T, Takahashi M, Toga H (2012) Sleep apnoea syndrome as a risk for mortality in elderly inpatients. J Int Med Res 40(2):601–611. doi: 10.1177/147323001204000222 CrossRefPubMedGoogle Scholar
  42. 42.
    Lee JE, Lee CH, Lee SJ, Ryu Y, Lee WH, Yoon IY, Rhee CS, Kim JW (2013) Mortality of patients with obstructive sleep apnea in Korea. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 9(10):997–1002. doi: 10.5664/jcsm.3068 Google Scholar
  43. 43.
    Marshall NS, Wong KK, Cullen SR, Knuiman MW, Grunstein RR (2014) Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Study cohort. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 10(4):355–362. doi: 10.5664/jcsm.3600 Google Scholar
  44. 44.
    Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, Colombo PC, Basner RC, Factor P, LeJemtel TH (2008) Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation 117(17):2270–2278. doi: 10.1161/CIRCULATIONAHA.107.741512 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Bradley TD, Floras JS (2009) Obstructive sleep apnoea and its cardiovascular consequences. Lancet 373:82–93. doi: 10.1016/S0140-6736(08)61622-0 CrossRefPubMedGoogle Scholar
  46. 46.
    Fleetham J, Ayas N, Bradley D, Ferguson K, Fitzpatrick M, George C, Hanly P, Hill F, Kimoff J, Kryger M, Morrison D, Series F, Tsai W (2006) Canadian Thoracic Society guidelines: diagnosis and treatment of sleep disordered breathing in adults. Can Respir J 13(7):387–392CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lin MT, Lin HH, Lee PL, Weng PH, Lee CC, Lai TC, Liu W, Chen CL (2015) Beneficial effect of continuous positive airway pressure on lipid profiles in obstructive sleep apnea: a meta-analysis. Sleep & breathing = Schlaf & Atmung 19(3):809–817. doi: 10.1007/s11325-014-1082-x CrossRefGoogle Scholar
  48. 48.
    Buchner NJ, Quack I, Woznowski M, Stahle C, Wenzel U, Rump LC (2011) Microvascular endothelial dysfunction in obstructive sleep apnea is caused by oxidative stress and improved by continuous positive airway pressure therapy. Respiration 82(5):409–417. doi: 10.1159/000323266 CrossRefPubMedGoogle Scholar
  49. 49.
    Ciccone MM, Favale S, Scicchitano P, Mangini F, Mitacchione G, Gadaleta F, Longo D, Iacoviello M, Forleo C, Quistelli G, Taddei S, Resta O, Carratu P (2012) Reversibility of the endothelial dysfunction after CPAP therapy in OSAS patients. Int J Cardiol 158(3):383–386. doi: 10.1016/j.ijcard.2011.01.065 CrossRefPubMedGoogle Scholar
  50. 50.
    Oyama J, Yamamoto H, Maeda T, Ito A, Node K, Makino N (2012) Continuous positive airway pressure therapy improves vascular dysfunction and decreases oxidative stress in patients with the metabolic syndrome and obstructive sleep apnea syndrome. Clin Cardiol 35(4):231–236. doi: 10.1002/clc.21010 CrossRefPubMedGoogle Scholar
  51. 51.
    Christou K, Kostikas K, Pastaka C, Tanou K, Antoniadou I, Gourgoulianis KI (2009) Nasal continuous positive airway pressure treatment reduces systemic oxidative stress in patients with severe obstructive sleep apnea syndrome. Sleep Med 10(1):87–94. doi: 10.1016/j.sleep.2007.10.011 CrossRefPubMedGoogle Scholar
  52. 52.
    Vitarelli A, Terzano C, Saponara M, Gaudio C, Mangieri E, Capotosto L, Pergolini M, D’Orazio S, Continanza G, Cimino E (2015) Assessment of right ventricular function in obstructive sleep apnea syndrome and effects of continuous positive airway pressure therapy: a pilot study. Can J Cardiol 31(7):823–831. doi: 10.1016/j.cjca.2015.01.029 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Otolaryngology Head and Neck Surgery & Center of Sleep MedicineShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina
  2. 2.Otolaryngological Institute of Shanghai Jiao Tong UniversityShanghaiChina
  3. 3.Clinical Research CenterShanghai Jiao Tong University School of MedicineShanghaiChina

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