Advertisement

Age and comorbidities are crucial predictors of mortality in severe obstructive sleep apnoea syndrome

      Highlights

      • Severe OSAS is associated with increased comorbid burden and all-cause mortality.
      • The prognostic role of comorbidity remains poorly defined.
      • Age and comorbidity are crucial contributors to increased mortality in severe OSAS.
      • Clustering of comorbidities allows identify clinically meaningful phenotypes

      Abstract

      Background

      Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disorder. The prognostic role of comorbidity in patients with OSAS and their role for risk stratification remain poorly defined.

      Methods

      We studied 1,592 patients with severe OSAS diagnosed by polysomnography. The primary outcome was all-cause mortality. The standardized mortality ratio (SMR) was estimated as the ratio of observed deaths to expected number of deaths in the general population. The expected numbers of deaths were derived using mortality rates from the general Apulian population. The association of comorbidities with all-cause mortality was assessed using multivariable Cox regression analysis. Finally, recursive-partitioning analysis was applied to identify the combinations of comorbidities that were most influential for mortality and to cluster the patients into risk groups according to individual comorbidities

      Results

      During 11,721 person-years of follow-up, 390 deaths (3.33 deaths/100 person-years) occurred. The median follow-up was 7 (4–10) years. The SMR was 1.47 (95% confidence intervals 1.33–1.63). Age, sex, obesity, cardiovascular diseases (CVD), moderate-to-severe chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD) and malignancy were independently associated with mortality risk. Recursive-partitioning analysis allowed distinguishing three clinical phenotypes differentially associated with mortality risk. The combination of CKD with CVDs or with moderate-to-severe COPD conferred the highest risk.

      Conclusions

      Severe OSAS is associated with increased risk for all-cause death. Age and comorbidity are crucial predictors of mortality in patients with severe OSAS. Clustering patients according to comorbidities allows identifying clinically meaningful phenotypes.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Jennum P.
        • Riha R.L.
        Epidemiology of sleep apnoea/hypopnoea syndrome and sleep-disordered breathing.
        Eur Respir J. 2009; 33: 907-914
        • Mokhlesi B.
        • Ham S.A.
        • Gozal D.
        The effect of sex and age on the comorbidity burden of OSA: an observational analysis from a large nationwide US health claims database.
        Eur Respir J. 2016; 47: 1162-1169
        • Benjafield A.V.
        • Ayas N.T.
        • Eastwood P.R.
        • Heinzer R.
        • Ip M.S.M.
        • Morrell M.J.
        • et al.
        Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis.
        Lancet Respir Med. 2019; 7: 687-698
      1. Armeni P., Borsoi L., Costa F., Donin G., Gupta A. Cost-of-illness study of Obstructive Sleep Apnea Syndrome (OSAS) in Italy. Università Bocconi. CERGAS-Centro di Ricerche dell'Assistenza Sanitaria e Sociale 2019. Available at: https://www.cergas.unibocconi.eu/wps/wcm/connect/ad0ba356-ea26-455d-b098-b66c60ef5011/Cost-of-illness+study+of+Obstructive+Sleep+Apnea+Syndrome+%28OSAS%29+in+Italy_Report%281%29.pdf?MOD=AJPERES&CVID=mMZQH7r.

        • Kapur V.K.
        • Auckley D.H.
        • Chowdhuri S.
        • Kuhlmann D.C.
        • Mehra R.
        • Ramar K.
        • et al.
        Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American academy of sleep medicine clinical practice guideline.
        J Clin Sleep Med. 2017; 13: 479-504
        • Lévy P.
        • Kohler M.
        • McNicholas W.T.
        • Barbé F.
        • McEvoy R.D.
        • Somers V.K.
        • et al.
        Obstructive sleep apnoea syndrome.
        Nat Rev Dis Primers. 2015; 1: 15015https://doi.org/10.1038/nrdp.2015.15
        • Patil S.P.
        • Ayappa I.A.
        • Caples S.M.
        • Kimoff R.J.
        • Patel S.R.
        • Harrod C.G.
        Treatment of adult obstructive sleep apnea with positive airway pressure: an American academy of sleep medicine systematic review, meta-analysis, and GRADE assessment.
        J Clin Sleep Med. 2019; 15: 301-334
        • Xie C.
        • Zhu R.
        • Tian Y.
        • Wang K.
        Association of obstructive sleep apnoea with the risk of vascular outcomes and all-cause mortality: a meta-analysis.
        BMJ Open. 2017; 7e013983https://doi.org/10.1136/bmjopen-2016-013983
        • Ge X.
        • Han F.
        • Huang Y.
        • Zhang Y.
        • Yang T.
        • Bai C.
        • et al.
        Is obstructive sleep apnea associated with cardiovascular and all-cause mortality?.
        PLoS One. 2013; 8: e69432https://doi.org/10.1371/journal.pone.0069432
        • Bonsignore M.R.
        • Baiamonte P.
        • Mazzuca E.
        • Castrogiovanni A.
        • Marrone O.
        Obstructive sleep apnea and comorbidities: a dangerous liaison.
        Multidiscip Respir Med. 2019; 14: 8https://doi.org/10.1186/s40248-019-0172-9
        • Appleton S.L.
        • Gill T.K.
        • Lang C.J.
        • Taylor A.W.
        • McEvoy R.D.
        • Stocks N.P.
        • et al.
        Prevalence and comorbidity of sleep conditions in Australian adults: 2016 Sleep Health Foundation national survey.
        Sleep Health. 2018; 4: 13-19
        • Chiang C.L.
        • Chen Y.T.
        • Wang K.L.
        • Su V.Y.
        • Wu L.A.
        • Perng D.W.
        • et al.
        Comorbidities and risk of mortality in patients with sleep apnea.
        Ann Med. 2017; 49: 377-383
        • Marin-Oto M.
        • Vicente E.E.
        • Marin J.M.
        Long term management of obstructive sleep apnea and its comorbidities.
        Multidiscip Respir Med. 2019; 14: 21https://doi.org/10.1186/s40248-019-0186-3
        • American Diabetes Association
        Classification and diagnosis of diabetes: standards of medical care in diabetes—2019.
        Diabetes Care. 2019; 42: S13-S28
      2. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2020 Report). Available at https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.0wms.pdf.

        • Kidney Disease: Improving Global Outcomes (KDIGO)
        KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.
        Kidney Int Suppl. 2013; 3: 1-150
        • Finkelstein D.R.
        • Muzykansky A.
        • Schoenfeld D.A.
        Comparing survival of a sample to that of a standard population.
        J Natl Cancer Inst. 2003; 95: 1434-1439
        • Lavie P.
        • Lavie L.
        • Herer P.
        All-cause mortality in males with sleep apnoea syndrome: declining mortality rates with age.
        Eur Respir J. 2005; 25: 514-520
        • Punjabi N.M.
        • Caffo B.S.
        • Goodwin J.L.
        • Gottlieb D.J.
        • Newman A.B.
        • O'Connor G.T.
        • et al.
        Sleep-disordered breathing and mortality: a prospective cohort study.
        PLoS Med. 2009; 6e1000132https://doi.org/10.1371/journal.pmed.1000132
        • Austad S.N.
        • Fischer K.E.
        Sex differences in lifespan.
        Cell Metab. 2016; 23: 1022-1033
        • Hainer V.
        • Aldhoon-Hainerová I.
        Obesity paradox does exist.
        Diabetes Care. 2013; 36: S276-5281
        • Chrysant S.G.
        • Chrysant G.S.
        The single use of body mass index for the obesity paradox is misleading and should be used in conjunction with other obesity indices.
        Postgrad Med. 2019; 131 (Mar): 96-102
        • Donini L.M.
        • Pinto A.
        • Giusti A.M.
        • Lenzi A.
        • Poggiogalle E.
        Obesity or BMI paradox? beneath the tip of the iceberg.
        Front Nutr. 2020; (May 7;7): 53https://doi.org/10.3389/fnut.2020.00053
        • GBD
        Causes of death collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the global burden of disease study 2016.
        Lancet. 2016; 2017: 1151-1210
        • GBD
        Chronic kidney disease collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the global burden of disease study 2017.
        Lancet. 2020; 395: 709-733
        • Shamsuzzaman A.S.
        • Gersh B.J.
        • Somers V.K.
        Obstructive sleep apnea: implications for cardiac and vascular disease.
        JAMA. 2003; 290: 1906-1914
        • Schlaich M.P.
        • Socratous F.
        • Hennebry S.
        • Eikelis N.
        • Lambert E.A.
        • Straznicky N.
        • et al.
        Sympathetic activation in chronic renal failure.
        J Am Soc Nephrol. 2009; 20: 933-939
        • Drager L.F.
        • McEvoy R.D.
        • Barbe F.
        • Lorenzi-Filho G.
        • Redline S.
        INCOSACT initiative (international collaboration of sleep apnea cardiovascular trialists). sleep apnea and cardiovascular disease: lessons from recent trials and need for team science.
        Circulation. 2017; 136: 1840-1850
        • Wang Y.
        • Hu K.
        • Liu K.
        • Li Z.
        • Yang J.
        • Dong Y.
        • et al.
        Obstructive sleep apnea exacerbates airway inflammation in patients with chronic obstructive pulmonary disease.
        Sleep Med. 2015; 16: 1123-1130
        • Narkiewicz K.
        • Kato M.
        • Phillips B.G.
        • Pesek C.A.
        • Davison D.E.
        • Somers V.K.
        Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea.
        Circulation. 1999; 100: 2332-2335
        • Kasai T.
        • Floras J.S.
        • Bradley T.D.
        Sleep apnea and cardiovascular disease: a bidirectional relationship.
        Circulation. 2012; 126: 1495-1510
        • Javaheri S.
        • Barbe F.
        • Campos-Rodriguez F.
        • Dempsey J.A.
        • Khayat R.
        • Javaheri S.
        • et al.
        Sleep apnea: types, mechanisms, and clinical cardiovascular consequences.
        J Am Coll Cardiol. 2017; 69: 841-858
        • Labarca G.
        • Dreyse J.
        • Drake L.
        • Jorquera J.
        • Barbe F.
        Efficacy of continuous positive airway pressure (CPAP) in the prevention of cardiovascular events in patients with obstructive sleep apnea: Systematic review and meta-analysis.
        Sleep Med Rev. 2020; 52101312https://doi.org/10.1016/j.smrv.2020.101312
        • Sánchez-de-la-Torre M.
        • Sánchez-de-la-Torre A.
        • Bertran S.
        • Abad J.
        • Duran-Cantolla J.
        • Cabriada V.
        • et al.
        Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.
        Lancet Respir Med. 2020; 8: 359-367
        • McEvoy R.D.
        • Antic N.A.
        • Heeley E.
        • Luo Y.
        • Ou Q.
        • Zhang X.
        • et al.
        CPAP for prevention of cardiovascular events in obstructive sleep apnea.
        N Engl J Med. 2016; 375: 919-931
        • Khan S.U.
        • Duran C.A.
        • Rahman H.
        • Lekkala M.
        • Saleem M.A.
        • Kaluski E.
        A meta-analysis of continuous positive airway pressure therapy in prevention of cardiovascular events in patients with obstructive sleep apnoea.
        Eur Heart J. 2018; 39: 2291-2297
        • Peker Y.
        • Glantz H.
        • Eulenburg C.
        • Wegscheider K.
        • Herlitz J.
        • Thunström E.
        Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled trial.
        Am J Respir Crit Care Med. 2016; 194: 613-620
        • Cowie M.R.
        • Woehrle H.
        • Wegscheider K.
        • Angermann C.
        • d'Ortho M.P.
        • Erdmann E.
        • et al.
        Adaptive servo-ventilation for central sleep apnea in systolic heart failure.
        N Engl J Med. 2015; 373: 1095-1110
        • Iseki K.
        • Tohyama K.
        • Matsumoto T.
        • Nakamura H.
        High Prevalence of chronic kidney disease among patients with sleep related breathing disorder (SRBD).
        Hypertens Res. 2008; 31: 249-255
        • Kim J.W.
        • Won T.B.
        • Rhee C.S.
        • Park Y.M.
        • Yoon I.Y.
        • Cho S.W.
        Polysomnographic phenotyping of obstructive sleep apnea and its implications in mortality in.
        Korea. Sci Rep. 2020; 10: 13207https://doi.org/10.1038/s41598-020-70039-5
        • Quan W.
        • Zheng D.
        • Douglas McEvoy R.
        • Barbe F.
        • Chen R.
        • Liu Z.
        • et al.
        High risk characteristics for recurrent cardiovascular events among patients with obstructive sleep apnoea in the SAVE study.
        EClinicalMedicine. 2018; 2-3: 59-65https://doi.org/10.1016/j.eclinm.2018.09.002
        • Williamson L.
        Obstructive sleep apnoea: latest surgical advances and considerations during the COVID-19 pandemic.
        Lancet Respir Med. 2020; 8: e98https://doi.org/10.1016/S2213-2600(20)30464-1
        • Batool-Anwar S.
        • Omobomi O.S.
        • Quan S.F.
        Impact of the novel coronavirus disease on treatment adherence and sleep duration in patients with obstructive sleep apnea treated with positive airway pressure.
        J Clin Sleep Med. 2020; 16: 1917-1920
        • Maas M.B.
        • Kim M.
        • Malkani R.G.
        • Abbott S.M.
        • Zee P.C.
        Obstructive sleep apnea and risk of COVID-19 infection, hospitalization and respiratory failure.
        Sleep Breath. 2020; : 1-3https://doi.org/10.1007/s11325-020-02203-0
        • Peker Y.
        • Celik Y.
        • Arbatli S.
        • Isik S.R.
        • Balcan B.
        • Karataş F.
        Effect of high-risk obstructive sleep apnea on clinical outcomes in adults with coronavirus disease 2019: a multicenter, prospective, observational cohort study.
        Ann Am Thorac Soc. 2021; https://doi.org/10.1513/AnnalsATS.202011-1409OC
        • Dodds S.
        • Williams L.J.
        • Roguski A.
        • Vennelle M.
        • Douglas N.J.
        • Kotoulas S.C.
        • et al.
        Mortality and morbidity in obstructive sleep apnoea-hypopnoea syndrome: results from a 30-year prospective cohort study.
        ERJ Open Res. 2020; 6 (00057-2020)https://doi.org/10.1183/23120541.00057-2020