Advertisement

Current Sleep Medicine Reports

, Volume 5, Issue 4, pp 225–233 | Cite as

Mild Sleep-Disordered Breathing and Cardiovascular Disease Risk

  • Salam Zeineddine
  • Jennifer L. Martin
  • M. Safwan BadrEmail author
Heart Disease and Sleep Disturbances (R Khayat, Section Editor)
  • 7 Downloads
Part of the following topical collections:
  1. Topical Collection on Heart Disease and Sleep Disturbances

Abstract

Purpose of Review

Sleep-disordered breathing, particularly obstructive sleep apnea (OSA), was identified to impact several health outcomes and physiopathological processes, most notably cardiovascular disease (CVD). However, much less research had addressed the impact of mild OSA as a risk factor for symptomatic CVD. The purpose of this review is to assess the evidence regarding mild OSA and its association with CVD and whether treatment of mild OSA is effective at preventing adverse cardiovascular outcomes.

Recent Findings

There is absence of recent large-scale randomized clinical trials that address the impact of mild OSA and its therapy on the risk of CVD. Findings from recent studies are inconsistent and do not support the use of continuous positive airway pressure therapy for the sole purpose of preventing adverse cardiovascular outcomes in patients with mild OSA.

Summary

There is limited or uncertain evidence pertaining to the impact of mild OSA and its therapy on CVD. Future research is mandated to further elucidate this critical topic.

Keywords

Sleep-disordered breathing Mild obstructive sleep apnea Cardiovascular disease 

Notes

Funding Information

Dr. Badr is supported by the Department of Veterans Affairs (VA RR&D 1I01RX002116-01) and NHLBI (R01HL130552). Dr. Martin is supported by the VA Greater Los Angeles Healthcare System, Geriatric Research, Education, and Clinical Center (GRECC); National Heart Lung and Blood Institute (Martin K24HL143055) of the National Institutes of Health.

Compliance with Ethical Standards

Disclaimer

The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, National Institutes of Health, or the U.S. Government.

Conflict of Interest

Salam Zeineddine and M. Safwan Badr each declare no conflicts of interest.

Jennifer Martin reports a grant from NIH/NHLBI during the conduct of the study and membership of the Board of Directors of the American Academy of Sleep Medicine.

Human and Animal Rights Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the sleep heart health study. Am J Respir Crit Care Med. 2001;163(1):19–25.PubMedGoogle Scholar
  2. 2.
    Chowdhuri S, Quan SF, Almeida F, Ayappa I, Batool-Anwar S, Budhiraja R, et al. An official American Thoracic Society research statement: impact of mild obstructive sleep apnea in adults. Am J Respir Crit Care Med. 2016;193(9):e37–54.PubMedGoogle Scholar
  3. 3.
    Medicine, A.A.o.S., International classification of Sleep Disorders, third edition. 2014.Google Scholar
  4. 4.
    Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5(3):263–76.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Patil SP, et al. Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of sleep medicine clinical practice guideline. J Clin Sleep Med. 2019;15(2):335–43.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Alessi C, Martin JL, Fiorentino L, Fung CH, Dzierzewski JM, Rodriguez Tapia JC, et al. Cognitive behavioral therapy for insomnia in older veterans using nonclinician sleep coaches: randomized controlled trial. J Am Geriatr Soc. 2016;64(9):1830–8.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Fung CH, et al. Efficacy of cognitive behavioral therapy for insomnia in older adults with occult sleep-disordered breathing. Psychosom Med. 2016;78(5):629–39.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, et al. Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol. 2017;69(7):841–58.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Ryan S. Mechanisms of cardiovascular disease in obstructive sleep apnoea. J Thorac Dis. 2018;10(Suppl 34):S4201–11.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia--revisited--the bad ugly and good: implications to the heart and brain. Sleep Med Rev. 2015;20:27–45.PubMedGoogle Scholar
  11. 11.
    Drager LF, Bortolotto LA, Lorenzi MC, Figueiredo AC, Krieger EM, Lorenzi-Filho G. Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2005;172(5):613–8.PubMedGoogle Scholar
  12. 12.
    Nanduri J, Nanduri RP. Cellular mechanisms associated with intermittent hypoxia. Essays Biochem. 2007;43:91–104.PubMedGoogle Scholar
  13. 13.
    Adedayo AM, et al. Obstructive sleep apnea and dyslipidemia: evidence and underlying mechanism. Sleep Breath. 2014;18(1):13–8.PubMedGoogle Scholar
  14. 14.
    Ip MS, Lam KS, Ho C, Tsang KW, Lam W. Serum leptin and vascular risk factors in obstructive sleep apnea. Chest. 2000;118(3):580–6.PubMedGoogle Scholar
  15. 15.
    Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation. 2012;126(12):1495–510.PubMedGoogle Scholar
  16. 16.
    Almendros I, Wang Y, Gozal D. The polymorphic and contradictory aspects of intermittent hypoxia. Am J Physiol Lung Cell Mol Physiol. 2014;307(2):L129–40.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association professional education Committee of the Council for high blood pressure research. Circulation. 2008;117(25):e510–26.PubMedGoogle Scholar
  18. 18.
    Hypertension, E.E.T.F.f.t.M.o.A. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC task force for the Management of Arterial Hypertension. J Hypertens. 2013;31(10):1925–38.Google Scholar
  19. 19.
    Peppard PE, et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378–84.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Goncalves SC, et al. Obstructive sleep apnea and resistant hypertension: a case-control study. Chest. 2007;132(6):1858–62.PubMedGoogle Scholar
  21. 21.
    Ohkubo T, et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens. 2002;20(11):2183–9.PubMedGoogle Scholar
  22. 22.
    Hla KM, Young T, Finn L, Peppard PE, Szklo-Coxe M, Stubbs M. Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin sleep cohort study. Sleep. 2008;31(6):795–800.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Ma Y, et al. Ambulatory blood pressure monitoring in Chinese patients with obstructive sleep apnea. J Clin Sleep Med. 2017;13(3):433–9.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhu YQ, Long Q, Wang C, Shuai XJ, Chen B, Kong J, et al. Relationship between sleep architecture and blood pressure dynamic change in patients with sleep apnea syndrome. Zhonghua Yi Xue Za Zhi. 2016;96(28):2220–3.PubMedGoogle Scholar
  25. 25.
    Guimarães TM, et al. Association between nondipping pattern and EndoPAT signal in patients with mild obstructive sleep apnea. Sleep Med. 2018;51:9–14.Google Scholar
  26. 26.
    Cano-Pumarega I, Durán-Cantolla J, Aizpuru F, Miranda-Serrano E, Rubio R, Martínez-Null C, et al. Obstructive sleep apnea and systemic hypertension: longitudinal study in the general population: the Vitoria sleep cohort. Am J Respir Crit Care Med. 2011;184(11):1299–304.PubMedGoogle Scholar
  27. 27.
    Marin JM, Agusti A, Villar I, Forner M, Nieto D, Carrizo SJ, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307(20):2169–76.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Fava C, Dorigoni S, Dalle Vedove F, Danese E, Montagnana M, Guidi GC, et al. Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic review and meta-analysis. Chest. 2014;145(4):762–71.PubMedGoogle Scholar
  29. 29.
    Pepin JL, et al. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010;182(7):954–60.PubMedGoogle Scholar
  30. 30.
    Javaheri S, et al. Sleep-disordered breathing and incident heart failure in older men. Am J Respir Crit Care Med. 2016;193(5):561–8.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Hla KM, Young T, Hagen EW, Stein JH, Finn LA, Nieto FJ, et al. Coronary heart disease incidence in sleep disordered breathing: the Wisconsin sleep cohort study. Sleep. 2015;38(5):677–84.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Gottlieb DJ, Yenokyan G, Newman AB, O'Connor GT, Punjabi NM, Quan SF, et al. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation. 2010;122(4):352–60.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Shah N, Redline S, Yaggi HK, Wu R, Zhao CG, Ostfeld R, et al. Obstructive sleep apnea and acute myocardial infarction severity: ischemic preconditioning? Sleep Breath. 2013;17(2):819–26.PubMedGoogle Scholar
  34. 34.
    Ludka O, Stepanova R, Sert-Kuniyoshi F, Spinar J, Somers VK, Kara T. Differential likelihood of NSTEMI vs STEMI in patients with sleep apnea. Int J Cardiol. 2017;248:64–8.PubMedGoogle Scholar
  35. 35.
    • Kendzerska T, et al. Sleep Apnea Increases the Risk of New Hospitalized Atrial Fibrillation: A Historical Cohort Study. Chest. 2018;154(6):1330–9 This study examined the relationship between newly diagnosed OSA and incident hospitalized atrial fibrillation (AF) over the subsequent 10 years in a large arrhythmia-free cohort.PubMedGoogle Scholar
  36. 36.
    Tung, P., et al., Obstructive and Central Sleep Apnea and the Risk of Incident Atrial Fibrillation in a Community Cohort of Men and Women. J Am Heart Assoc, 2017. 6(7).Google Scholar
  37. 37.
    Szymanski FM, Filipiak KJ, Platek AE, Hrynkiewicz-Szymanska A, Kotkowski M, Kozluk E, et al. Presence and severity of obstructive sleep apnea and remote outcomes of atrial fibrillation ablations - a long-term prospective, cross-sectional cohort study. Sleep Breath. 2015;19(3):849–56.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Lee CJ, Kim TH, Park S, Pak HN. Obstructive sleep apnea is closely related to cardiovascular risk factors, but not to clinical recurrence of atrial fibrillation after catheter ablation: an analysis of atrial fibrillation patients. Pulse (Basel). 2018;6(1–2):103–11.Google Scholar
  39. 39.
    Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O'Connor GT, Resnick HE, et al. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med. 2010;182(2):269–77.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Fu Y, Xia Y, Yi H, Xu H, Guan J, Yin S. Meta-analysis of all-cause and cardiovascular mortality in obstructive sleep apnea with or without continuous positive airway pressure treatment. Sleep Breath. 2017;21(1):181–9.PubMedGoogle Scholar
  41. 41.
    • Aurora RN, et al. Obstructive Sleep Apnea during REM Sleep and Cardiovascular Disease. Am J Respir Crit Care Med. 2018;197(5):653–60 This study examined the association between OSA during REM sleep and a composite cardiovascular endpoint in a large sample from the Sleep Heart Health Study, with and without prevalent cardiovascular disease.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Marshall NS, Wong KK, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton health study cohort. J Clin Sleep Med. 2014;10(4):355–62.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Korostovtseva LS, Sviryaev YV, Zvartau NE, Konradi AO, Kalinkin AL. Prognosis and cardiovascular morbidity and mortality in prospective study of hypertensive patients with obstructive sleep apnea syndrome in St Petersburg. Russia Med Sci Monit. 2011;17(3):CR146–53.PubMedGoogle Scholar
  44. 44.
    Schipper MH, Jellema K, Thomassen BJW, Alvarez-Estevez D, Verbraecken J, Rijsman RM. Stroke and other cardiovascular events in patients with obstructive sleep apnea and the effect of continuous positive airway pressure. J Neurol. 2017;264(6):1247–53.PubMedGoogle Scholar
  45. 45.
    Kendzerska T, Gershon AS, Hawker G, Leung RS, Tomlinson G. Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: a decade-long historical cohort study. PLoS Med. 2014;11(2):e1001599.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31(8):1071–8.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O'Connor GT, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med. 2009;6(8):e1000132.PubMedPubMedCentralGoogle Scholar
  48. 48.
    • Haarmann H, et al. Morbidity and mortality in patients with cardiovascular risk factors and obstructive sleep apnoea: results from the DIAST-CHF cohort. Respir Med. 2019;154:127–32 This large prospective study investigated the association between OSA and cardiovascular morbidity and mortality in a cohort of patients with cardiovascular risk factors. All severities of OSA were analyzed.PubMedGoogle Scholar
  49. 49.
    Pan L, Xie X, Liu D, Ren D, Guo Y. Obstructive sleep apnoea and risks of all-cause mortality: preliminary evidence from prospective cohort studies. Sleep Breath. 2016;20(1):345–53.PubMedGoogle Scholar
  50. 50.
    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;7(12):e013983.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Lei Q, Lv Y, Li K, Ma L, du G, Xiang Y, et al. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a systematic review and meta-analysis of six randomized controlled trials. J Bras Pneumol. 2017;43(5):373–9.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Yu J, Zhou Z, McEvoy R, Anderson CS, Rodgers A, Perkovic V, et al. Association of Positive Airway Pressure with Cardiovascular Events and Death in adults with sleep apnea: A systematic review and meta-analysis. JAMA. 2017;318(2):156–66.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Abuzaid AS, al Ashry HS, Elbadawi A, Ld H, Saad M, Elgendy IY, et al. Meta-analysis of cardiovascular outcomes with continuous positive airway pressure therapy in patients with obstructive sleep apnea. Am J Cardiol. 2017;120(4):693–9.PubMedGoogle Scholar
  54. 54.
    da Silva Paulitsch, F. And L. Zhang, Continuous positive airway pressure for adults with obstructive sleep apnea and cardiovascular disease: a meta-analysis of randomized trials. Sleep Med, 2019. 54: p. 28–34.PubMedGoogle Scholar
  55. 55.
    Wang X, Zhang Y, Dong Z, Fan J, Nie S, Wei Y. Effect of continuous positive airway pressure on long-term cardiovascular outcomes in patients with coronary artery disease and obstructive sleep apnea: a systematic review and meta-analysis. Respir Res. 2018;19(1):61.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Liu L, et al. Continuous positive airway pressure in patients with obstructive sleep apnea and resistant Hypertension: A meta-analysis of randomized controlled trials. J Clin Hypertens (Greenwich). 2016;18(2):153–8.Google Scholar
  57. 57.
    Tuomilehto HP, Seppä JM, Partinen MM, Peltonen M, Gylling H, Tuomilehto JO, et al. Lifestyle intervention with weight reduction: first-line treatment in mild obstructive sleep apnea. Am J Respir Crit Care Med. 2009;179(4):320–7.PubMedGoogle Scholar
  58. 58.
    •• McEvoy RD, et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016;375(10):919–31 This study represents the most important investigation into SDB in recent times given its comprehensive methodology and statistical power. Its objective was to analyze whether treatment with CPAP can prevent major cardiovascular events.PubMedGoogle Scholar
  59. 59.
    10/29/2018 8/16/2019]; Available from: https://clinicaltrials.gov/ct2/show/study/NCT01335087.
  60. 60.
    Buchner NJ, Sanner BM, Borgel J, Rump LC. Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. Am J Respir Crit Care Med. 2007;176(12):1274–80.PubMedGoogle Scholar
  61. 61.
    Wu X, et al. Screening and managing obstructive sleep apnoea in nocturnal heart block patients: an observational study. Respir Res. 2016;17:16.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Kawano Y, Tamura A, Ono K, Kadota J. Association between obstructive sleep apnea and premature supraventricular contractions. J Cardiol. 2014;63(1):69–72.PubMedGoogle Scholar
  63. 63.
    Vrijens B, et al. Current situation of medication adherence in Hypertension. Front Pharmacol. 2017;8:100.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Salam Zeineddine
    • 1
  • Jennifer L. Martin
    • 2
  • M. Safwan Badr
    • 3
    Email author
  1. 1.Department of Pulmonary, Critical Care and Sleep Medicine, John D. Dingell Veterans Affairs Medical CenterWayne State University School of MedicineDetroitUSA
  2. 2.VA Greater Los Angeles Healthcare SystemUniversity of CaliforniaLos AngelesUSA
  3. 3.Chair, Department of Internal Medicine, University Health CenterWayne State University School of MedicineDetroitUSA

Personalised recommendations