PDF herunterladen
Semin Respir Crit Care Med
DOI: 10.1055/a-2517-7880
Review Article

Pulmonary Embolism and Obstructive Sleep Apnea

Alberto García-Ortega
1   Respiratory Department, Doctor Peset University Hospital, Valencia, Spain
2   Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
,
Ana Pedro-Tudela
1   Respiratory Department, Doctor Peset University Hospital, Valencia, Spain
2   Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
,
Laura Taberner-Lino
1   Respiratory Department, Doctor Peset University Hospital, Valencia, Spain
2   Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
,
Esther Barreiro
3   Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
4   Pulmonology Department, Hospital del Mar, Barcelona, Spain
5   Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain
6   Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
,
Miguel Ángel Martínez-García
6   Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
7   Respiratory Department, La Fe University and Polytechnic Hospital, Valencia, Spain
,
Grace Oscullo
7   Respiratory Department, La Fe University and Polytechnic Hospital, Valencia, Spain
8   The Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
› Institutsangaben Funding None.
› Weitere Informationen
    Lizenzen und Reprints

Abstract

Pulmonary embolism (PE) and obstructive sleep apnea (OSA) remain a major health issue worldwide with potential overlapping pathophysiological mechanisms. PE, the most severe form of venous thromboembolism, is associated with high morbidity and mortality, presenting challenges in management and prevention, especially in high-risk populations. OSA is a prevalent condition characterized by repeated episodes of upper airway closure resulting in intermittent hypoxia and sleep fragmentation. Although the understanding of epidemiological and pathogenic relationships between OSA and PE is still limited, current data suggest that interactions between these two conditions appear to be relevant. OSA is emerging as a novel risk factor for PE, potentially affecting all components of Virchow's triad: hypercoagulability, endothelial dysfunction, and venous stasis. Epidemiological studies indicate a high prevalence of undiagnosed OSA in acute PE patients. Moderate-to-severe OSA has been linked to worse clinical presentations and outcomes. Furthermore, OSA has been associated with increased risks of PE recurrence and mortality. Future research directions should include clarifying the bidirectional relationship between these conditions and evaluating the effectiveness and safety of continuous positive airway pressure therapy in improving outcomes in patients with concurrent acute PE and OSA.

Keywords

pulmonary embolism - sleep apnea - coagulation - inflammation - sleep-disordered breathing - venous thromboembolism


Publikationsverlauf

Accepted Manuscript online:
22. Januar 2025

Artikel online veröffentlicht:
18. Februar 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Bikdeli B, Monreal M, Jiménez D. Pulmonary embolism in Europe remains a cause of concern despite declining deaths. Lancet Respir Med 2020; 8 (03) 222-224
    CrossrefPubMedSuche in Google Scholar
  • 2 Leidi A, Bex S, Righini M, Berner A, Grosgurin O, Marti C. Risk stratification in patients with acute pulmonary embolism: current evidence and perspectives. J Clin Med 2022; 11 (09) 2533
    CrossrefPubMedSuche in Google Scholar
  • 3 Ramírez P, Otero R, Barberà JA. Pulmonary chronic thromboembolic disease. Arch Bronconeumol 2020; 56 (05) 314-321
    CrossrefPubMedSuche in Google Scholar
  • 4 Alikhan R, Peters F, Wilmott R, Cohen AT. Fatal pulmonary embolism in hospitalised patients: a necropsy review. J Clin Pathol 2004; 57 (12) 1254-1257
    CrossrefPubMedSuche in Google Scholar
  • 5 Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009; 373 (9657) 82-93
    CrossrefPubMedSuche in Google Scholar
  • 6 Sánchez-de-la-Torre M, Campos-Rodriguez F, Barbé F. Obstructive sleep apnoea and cardiovascular disease. Lancet Respir Med 2013; 1 (01) 61-72
    CrossrefPubMedSuche in Google Scholar
  • 7 Martinez-Garcia MA, Campos-Rodriguez F, Gozal D. Obstructive sleep apnoea in acute coronary syndrome. Lancet Respir Med 2020; 8 (04) e15
    CrossrefPubMedSuche in Google Scholar
  • 8 Gabryelska A, Łukasik ZM, Makowska JS, Białasiewicz P. Obstructive sleep apnea: From intermittent hypoxia to cardiovascular complications via blood platelets. Front Neurol 2018; 9: 635
    CrossrefPubMedSuche in Google Scholar
  • 9 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
    CrossrefPubMedSuche in Google Scholar
  • 10 Liak C, Fitzpatrick M. Coagulability in obstructive sleep apnea. Can Respir J 2011; 18 (06) 338-348
    CrossrefPubMedSuche in Google Scholar
  • 11 Krieger AC, Anand R, Hernandez-Rosa E. et al. Increased platelet activation in sleep apnea subjects with intermittent hypoxemia. Sleep Breath 2020; 24 (04) 1537-1547
    CrossrefPubMedSuche in Google Scholar
  • 12 García-Ortega A, Mañas E, López-Reyes R. et al. Obstructive sleep apnoea and venous thromboembolism: pathophysiological links and clinical implications. Eur Respir J 2019; 53 (02) 1800893
    CrossrefPubMedSuche in Google Scholar
  • 13 Toukh M, Pereira EJ, Falcon BJ. et al. CPAP reduces hypercoagulability, as assessed by thromboelastography, in severe obstructive sleep apnoea. Respir Physiol Neurobiol 2012; 183 (03) 218-223
    CrossrefPubMedSuche in Google Scholar
  • 14 Robinson GV, Pepperell JCT, Segal HC, Davies RJO, Stradling JR. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 2004; 59 (09) 777-782
    CrossrefPubMedSuche in Google Scholar
  • 15 von Känel R, Loredo JS, Ancoli-Israel S, Mills PJ, Natarajan L, Dimsdale JE. Association between polysomnographic measures of disrupted sleep and prothrombotic factors. Chest 2007; 131 (03) 733-739
    CrossrefPubMedSuche in Google Scholar
  • 16 Phillips CL, McEwen BJ, Morel-Kopp MC. et al. Effects of continuous positive airway pressure on coagulability in obstructive sleep apnoea: a randomised, placebo-controlled crossover study. Thorax 2012; 67 (07) 639-644
    CrossrefPubMedSuche in Google Scholar
  • 17 Haus E. Chronobiology of hemostasis and inferences for the chronotherapy of coagulation disorders and thrombosis prevention. Adv Drug Deliv Rev 2007; 59 (9-10): 966-984
    CrossrefPubMedSuche in Google Scholar
  • 18 Wang J, Yu W, Gao M. et al. Impact of obstructive sleep apnea syndrome on endothelial function, arterial stiffening, and serum inflammatory markers: an updated meta-analysis and metaregression of 18 studies. J Am Heart Assoc 2015; 4 (11) e002454
    CrossrefPubMedSuche in Google Scholar
  • 19 Schwarz EI, Puhan MA, Schlatzer C, Stradling JR, Kohler M. Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: a systematic review and meta-analysis. Respirology 2015; 20 (06) 889-895
    CrossrefPubMedSuche in Google Scholar
  • 20 Xie J, Wei YX, Liu S, Zhang W, Zhang XF, Li J. obstructive sleep apnea hypopnea syndrome as a reason for active management of pulmonary embolism. Chin Med J (Engl) 2015; 128 (16) 2147-2153
    CrossrefPubMedSuche in Google Scholar
  • 21 Raj R, Paturi A, Ahmed MA, Thomas SE, Gorantla VR. Obstructive sleep apnea as a risk factor for venous thromboembolism: a systematic review. Cureus 2022; 14 (02) e22729
    PubMedSuche in Google Scholar
  • 22 Alonso-Fernández A, de la Peña M, Romero D. et al. Association between obstructive sleep apnea and pulmonary embolism. Mayo Clin Proc 2013; 88 (06) 579-587
    CrossrefPubMedSuche in Google Scholar
  • 23 Barbero E, Mañas E, Bikdeli B. et al. Untreated obstructive sleep apnea and cardiovascular outcomes in patients with acute symptomatic pulmonary embolism. Thromb Res 2022; 214: 87-92
    CrossrefPubMedSuche in Google Scholar
  • 24 Arnulf I, Merino-Andreu M, Perrier A, Birolleau S, Similowski T, Derenne JP. Obstructive sleep apnea and venous thromboembolism. JAMA 2002; 287 (20) 2655-2656
    CrossrefPubMedSuche in Google Scholar
  • 25 Kezban OS, Ali NA, Umran T. et al. Is obstructive sleep apnea syndrome a risk factor for pulmonary thromboembolism?. Chin Med J (Engl) 2012; 125 (20) 3712-3718
    PubMedSuche in Google Scholar
  • 26 Kosovalı D, Uyar M, Elbek O. et al. Obstructive sleep apnea is prevalent in patients with pulmonary embolism. Clin Invest Med 2013; 36 (06) E277-E281
    CrossrefPubMedSuche in Google Scholar
  • 27 Berghaus TM, Faul C, Unterer F, Thilo C, von Scheidt W, Schwaiblmair M. Acute pulmonary embolism in patients with obstructive sleep apnoea: does it affect the severity of sleep-disordered breathing?. Sleep Breath 2012; 16 (04) 1267-1269
    CrossrefPubMedSuche in Google Scholar
  • 28 Konnerth D, Schwarz F, Probst M. et al. Is acute pulmonary embolism more severe in the presence of obstructive sleep apnea? Results from an observational cohort study. J Thromb Thrombolysis 2018; 46 (02) 253-259
    CrossrefPubMedSuche in Google Scholar
  • 29 Arzt M, Luigart R, Schum C. et al; “Circulation and Sleep” working group of the German Society of Sleep Research and Sleep Medicine (DGSM). Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism. Eur Respir J 2012; 40 (04) 919-924
    CrossrefPubMedSuche in Google Scholar
  • 30 García-Ortega A, Oscullo G, Mañas-Baena E. et al; ESAET investigators. Changes in sleep-disordered breathing from the acute to the stable phase of pulmonary embolism: The ESAET study. Sleep Med 2023; 112: 88-95
    CrossrefPubMedSuche in Google Scholar
  • 31 Chou KT, Huang CC, Chen YM. et al. Sleep apnea and risk of deep vein thrombosis: a non-randomized, pair-matched cohort study. Am J Med 2012; 125 (04) 374-380
    CrossrefPubMedSuche in Google Scholar
  • 32 Lin CC, Keller JJ, Kang JH, Hsu TC, Lin HC. Obstructive sleep apnea is associated with an increased risk of venous thromboembolism. J Vasc Surg Venous Lymphat Disord 2013; 1 (02) 139-145
    CrossrefPubMedSuche in Google Scholar
  • 33 García-Ortega A, Mañas E, Oscullo G. Tromboembolia de pulmón y apnea obstructiva del sueño: una relación bidireccional. Arch Bronconeumol (Engl Ed) 2019; 55 (08) 399-400
    CrossrefPubMedSuche in Google Scholar
  • 34 Genuardi MV, Rathore A, Ogilvie RP. et al. Incidence of VTE in patients with OSA: a cohort study. Chest 2022; 161 (04) 1073-1082
    CrossrefPubMedSuche in Google Scholar
  • 35 Huang Z, Zheng Z, Pang L. et al. The association between obstructive sleep apnea and venous thromboembolism: a bidirectional two-sample mendelian randomization study. Thromb Haemost 2024; 124 (11) 1061-1074
    Thieme ConnectPubMedSuche in Google Scholar
  • 36 García-Ortega A, Mora VM, Lobo JL. Respiratory comorbidity and pulmonary embolism. Arch Bronconeumol 2023; 59 (03) 131-133
    CrossrefPubMedSuche in Google Scholar
  • 37 Jiménez D, Aujesky D, Moores L. et al; RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170 (15) 1383-1389
    CrossrefPubMedSuche in Google Scholar
  • 38 Alonso-Fernández A, Toledo-Pons N, García-Río F. Obstructive sleep apnea and venous thromboembolism: overview of an emerging relationship. Sleep Med Rev 2020; 50: 101233
    CrossrefPubMedSuche in Google Scholar
  • 39 Zhang W, Ding Y. Impact of obstructive sleep apnea on outcomes of pulmonary embolism: a systematic review and meta–analysis. Exp Ther Med 2023; 25 (03) 120
    CrossrefPubMedSuche in Google Scholar
  • 40 Geissenberger F, Schwarz F, Probst M. et al. Obstructive sleep apnea is associated with pulmonary artery thrombus load, disease severity, and survival in acute pulmonary embolism. Clin Res Cardiol 2020; 109 (01) 13-21
    CrossrefPubMedSuche in Google Scholar
  • 41 Toledo-Pons N, Alonso-Fernández A, de la Peña M. et al. Obstructive sleep apnea is associated with worse clinical-radiological risk scores of pulmonary embolism. J Sleep Res 2020; 29 (02) e12871
    CrossrefPubMedSuche in Google Scholar
  • 42 Chen J, Cao Y, Li Z, Dong L. Association between the severity of obstructive sleep apnea and the risk stratification of acute pulmonary embolism. Clin Appl Thromb Hemost 2023; 29: 10 760296231175654
    CrossrefPubMedSuche in Google Scholar
  • 43 Xu J, Wang X, Meng F. et al. The role of obstructive sleep apnea on the prognosis of pulmonary embolism: a systemic review and meta-analysis. Sleep Breath 2021; 25 (03) 1419-1426
    CrossrefPubMedSuche in Google Scholar
  • 44 Huang Z, Duan A, Zhao Z. et al. Impact of obstructive sleep apnea on disease severity and adverse outcomes in patients with acute pulmonary embolism. Nat Sci Sleep 2023; 15: 705-717
    CrossrefPubMedSuche in Google Scholar
  • 45 Seckin ZI, Helmi H, Weister TJ, Lee A, Festic E. Acute pulmonary embolism in patients with obstructive sleep apnea: frequency, hospital outcomes, and recurrence. J Clin Sleep Med 2020; 16 (07) 1029-1036
    CrossrefPubMedSuche in Google Scholar
  • 46 Le Mao R, Jiménez D, Bikdeli B. et al. Prognostic impact of obstructive sleep apnea in patients presenting with acute symptomatic pulmonary embolism. Thromb Haemost 2020; 121: 808-815
    PubMedSuche in Google Scholar
  • 47 García Suquia A, Alonso-Fernández A, de la Peña M. et al. High D-dimer levels after stopping anticoagulants in pulmonary embolism with sleep apnoea. Eur Respir J 2015; 46 (06) 1691-1700
    CrossrefPubMedSuche in Google Scholar
  • 48 Alonso-Fernández A, Suquia AG, de la Peña M. et al. OSA is a risk factor for recurrent VTE. Chest 2016; 150 (06) 1291-1301
    CrossrefPubMedSuche in Google Scholar
  • 49 Jiang X, Yongxiang W, Wei Z. et al. Higher dose of warfarin for patients with pulmonary embolism complicated by obstructive sleep apnea hypopnea syndrome. Heart Lung 2014; 43 (04) 358-362
    CrossrefPubMedSuche in Google Scholar
  • 50 Al Mukdad M, Al-Badriyeh D, Elewa HF. Cost-effectiveness evaluations among the direct oral anticoagulants for the prevention and treatment of venous thromboembolism: systematic review. Clin Appl Thromb Hemost 2019; 25: 10 76029619849103
    CrossrefPubMedSuche in Google Scholar
  • 51 Kim NH, D'Armini AM, Delcroix M. et al. Chronic thromboembolic pulmonary disease. Eur Respir J 2024; 64 (04) 2401294
    CrossrefPubMedSuche in Google Scholar
  • 52 von Känel R, Natarajan L, Ancoli-Israel S. et al. Effect of continuous positive airway pressure on day/night rhythm of prothrombotic markers in obstructive sleep apnea. Sleep Med 2013; 14 (01) 58-65
    CrossrefPubMedSuche in Google Scholar
  • 53 Javaheri S, Javaheri S, Gozal D. et al. Treatment of OSA and its impact on cardiovascular disease, part 2: JACC state-of-the-art review. J Am Coll Cardiol 2024; 84 (13) 1224-1240
    CrossrefPubMedSuche in Google Scholar
  • 54 Mañas E, Barbero E, Chiluiza D. et al; POPE Investigators. Impact of obstructive sleep apnea on cardiovascular outcomes in patients with acute symptomatic pulmonary embolism: rationale and methodology for the POPE study. Clin Cardiol 2017; 40 (12) 1182-1188
    CrossrefPubMedSuche in Google Scholar
  • 55 Berghaus TM, Witkowska A, Wagner T, Faul C, Schwaiblmair M, von Scheidt W. Obstructive sleep apnea might trigger acute pulmonary embolism: results from a cohort study. Clin Res Cardiol 2016; 105 (11) 938-943
    CrossrefPubMedSuche in Google Scholar