Meta-analysis of all-cause and cardiovascular mortality in obstructive sleep apnea with or without continuous positive airway pressure treatment
- 1.4k Downloads
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.
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.
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).
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.
KeywordsObstructive sleep apnea All-cause mortality Cardiovascular mortality Meta-analysis
Compliance with ethical standards
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 was not necessary for this meta-analysis, as only identified pooled data from previously approved individual studies were used.
Informed consent was obtained from all individual participants included in the study.
- 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
- 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
- 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
- 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.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
- 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.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.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
- 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
- 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
- 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.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
- 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
- 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.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.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.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.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