Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions

Moderate sleep apnoea: a “silent” disorder, or not a disorder at all?

Edward O. Bixler, Alexandros N. Vgontzas, Jordan Gaines, Julio Fernandez-Mendoza, Susan L. Calhoun, Duanping Liao
European Respiratory Journal 2016 47: 23-26; DOI: 10.1183/13993003.01955-2015
Edward O. Bixler
1Sleep Research and Treatment Center, Dept of Psychiatry, Penn State University College of Medicine, Hershey, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ebixler@hmc.psu.edu
Alexandros N. Vgontzas
1Sleep Research and Treatment Center, Dept of Psychiatry, Penn State University College of Medicine, Hershey, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jordan Gaines
1Sleep Research and Treatment Center, Dept of Psychiatry, Penn State University College of Medicine, Hershey, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julio Fernandez-Mendoza
1Sleep Research and Treatment Center, Dept of Psychiatry, Penn State University College of Medicine, Hershey, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan L. Calhoun
1Sleep Research and Treatment Center, Dept of Psychiatry, Penn State University College of Medicine, Hershey, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Duanping Liao
2Dept of Public Health Sciences, Penn State University College of Medicine, Hershey, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

New ERJ study adds to the evidence casting doubt on the utility of recommended cut-offs for sleep apnoea treatment http://ow.ly/VgjBL

Most sleep clinicians and scientists will agree that if a patient with sleep apnoea is symptomatic and has an apnoea/hypopnea index (AHI) of more than 15 events per hour, he or she deserves treatment. However, there is a large group of patients with mild and moderate sleep apnoea who are asymptomatic. For these individuals, the decision of when to treat is a grey area, and current guidelines leave clinicians wondering what to do.

Arnardottir et al. [1] from the University Hospital of Iceland studied a large general population sample of middle-aged individuals using polysomnographic sleep recordings, questionnaires and the psychomotor vigilance test (PVT). Of the 415 subjects, 12.5% had moderate obstructive sleep apnoea (OSA; AHI between 15 and 30), 2.9% had severe OSA (AHI ≥30), and 3.6% were already diagnosed and treated for OSA. Interestingly, no relationship was found between AHI and subjective sleepiness or clinical symptoms, whereas a relationship with objective vigilance, as measured by the PVT, was found only with those with AHI  ≥30. Furthermore, subjects with moderate or severe OSA were not more likely to have cardiometabolic disease than subjects with no or mild OSA. These results raise the question of whether the current cut-off of AHI ≥15 as a sole criterion is appropriate for diagnosis and treatment of OSA.

In 1998, we first reported, using the Penn State Adult Cohort, a different frequency and pattern of prevalence of OSA based on AHI solely versus based on a combination of AHI and presence of clinical symptoms (i.e. sleepiness and/or cardiometabolic disorders) [2]. The prevalence of OSA based on AHI alone was two to three times the prevalence of OSA based on laboratory and clinical criteria. Furthermore, based on AHI alone, the prevalence of OSA increased linearly, reaching its peak at very old age, whereas the prevalence based on combined criteria peaked at the age of 55 years for men and 65 years for women, then declined steeply (figure 1) [2, 3]. In addition, oxygen desaturation in older individuals was significantly less compared to that in younger individuals, suggesting the possibility that OSA in the elderly is less severe. Together, these findings suggested that the sleep field should re-evaluate the current criteria for diagnosis and treatment in this age group.

FIGURE 1
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 1

Age distribution of prevalence of obstructive sleep apnoea (OSA) by decade (apnoea/hypopnoea index ≥15 and presence of daytime symptoms). Prevalence peaks at age 55 years for men and 65 years for women. Data adapted from Bixler et al. [2] and Bixler et al. [3].

These early observations were further strengthened by another report in the same large cohort on the association of hypertension and OSA. We reported that AHI, controlled for relevant confounding variables, was independently associated with hypertension [4]. In addition, this study confirmed that the strength of the association between AHI and blood pressure was strongest in the youngest (figure 2). These findings further supported the implication that OSA in older individuals is not an independent risk factor for hypertension.

FIGURE 2
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 2

Age distribution of the odds of hypertension by decade with the presence of apnoea/hypopnoea index ≥15, adjusting for age, body mass index, gender, menopause and/or hormone replacement therapy. Data adapted from Bixler et al. [4].

The findings from prospective studies are equally interesting and surprising, particularly in terms of mortality risk. In an 18-year follow-up of the Wisconsin Sleep Cohort [5], an increased hazard ratio was reported only for severe OSA (AHI  ≥30), whereas the hazard ratio for mortality associated with moderate OSA (AHI  ≥15 but <30), was negligible. Similar findings were reported in an 8-year follow-up of the Sleep Heart Health Study [6]. Furthermore, in an elderly cohort (≥65 years), Lavie and Lavie [7] reported that mortality was not increased, even in those with respiratory disturbance index (RDI) >40 events per hour, whereas moderate OSA (RDI  ≥20 but <40) was even associated with an “unexpected survival advantage.” In another clinical cohort of men with OSA that were followed for 10 years, no association was found between mild/moderate OSA (AHI  ≥5 but <30) and mortality [8]. Combined, these results suggest that untreated moderate OSA is not associated with mortality, even after a long follow-up period (up to 20 years); in fact, in the elderly, moderate OSA might even have a protective effect [7].

The findings of prospective studies on the association of moderate OSA with cardiometabolic disorders are inconsistent and of rather modest impact. In the Sleep Heart Health Study, OSA was significantly associated with incident stroke only in men whose AHI was >20, but not in women in that apnoea range [9]. In the Wisconsin Sleep Cohort, the incidence of stroke was not associated with an AHI of <20, whereas it was significantly elevated in those subjects with AHI  ≥20 [10]. In terms of cardiovascular problems, the Sleep Heart Health Study reported that incident coronary heart disease and heart failure were not significantly associated with moderate OSA (AHI  ≥15 but <30), though there was a significant association with AHI ≥30 in men ≤70 years old; however, the risk of these cardiac problems was not increased for older men or women, even with an AHI  ≥30 [11]. In the Wisconsin Sleep Cohort, an AHI ≥15 was not associated with a significant risk for diabetes 4 years after the baseline measure [12]. In contrast with these findings, mild-to-moderate OSA was associated with a significant risk for development of hypertension in this cohort [13]; however, the potential confounding effects of age, gender and obesity were not examined. Also from the Wisconsin Sleep Cohort, minimum (but not mean) arterial oxygen saturation measured by pulse oximetry (SpO2) was associated with future carotid plaques. Interestingly, in this study, the use of continuous positive airway pressure (CPAP) did not change the association between minimum SpO2 and carotid atherosclerosis [14]. We should note that treatment of OSA with CPAP does not improve inflammation in these patients [15–17], which suggests that the association between OSA and hypertension or carotid atherosclerosis may be mediated by inflammation itself and not apnoeas/hypopneas. There is currently a gap in the literature, with a lack of studies on the association of moderate OSA in the presence of comorbid cardiometabolic disorders, as well as future fatal and non-fatal health sequelae.

Another concern is the association of sleepiness and impaired performance with OSA. In the present study by Arnardottir et al. [1], no association was found between sleepiness and OSA, whereas an effect on performance was found only in those with an AHI  ≥30. This is consistent with other population samples that have reported that only one out of five people with OSA complain of sleepiness [18–20]. Nevertheless, sleepiness is a more frequent symptom in clinical samples and of concern to patients, clinicians and public health authorities. A factor to consider in understanding this association is the evidence that other comorbid factors, such as obesity, are much stronger risk factors than AHI for excessive daytime sleepiness [19, 21]. In a large population cohort, it has been shown that obesity, depression, diabetes and young age are much stronger risk factors for daytime sleepiness than AHI [19]. Furthermore, obesity and depression, but not OSA, are risk factors for incident daytime sleepiness [22]. This may explain why, in clinical populations of apnoeics, the majority of the patients are obese, young to middle age, and depressed in contrast to the general population cohorts.

Obesity has been well established as a contributing factor for clinical outcomes associated with AHI. However, there is also strong evidence that metabolic aberrations related, but not exclusive, to obesity (i.e. inflammation, insulin resistance) are the primary mechanistic pathway. An early finding demonstrated in several population samples that pre-menopausal women were protected from OSA, and that post-menopausal women on hormone replacement therapy continued to be protected [3, 23, 24]. In a secondary analysis of a study in the Women's Health Initiative, it has been shown that women randomised to hormone replacement therapy had reduced insulin resistance [25]. In addition, several studies have reported a high risk for both OSA and excessive daytime sleepiness in women with polycystic ovary syndrome, a condition associated with hyperandrogenism and insulin resistance [26, 27]. These findings support the position that metabolic factors associated with gender play a more significant role than AHI in the association of OSA with clinical outcomes.

It is now widely accepted that the metabolic syndrome is the mechanistic link between AHI and cardiovascular outcomes, suggesting that central obesity (e.g. waist circumference) may be a better surrogate marker of cardiovascular risk than body mass index. Visceral adiposity, inflammation and insulin resistance, key components of the underlying pathophysiology of the metabolic syndrome, are the pathways leading to OSA or linking OSA to its cardiometabolic sequelae. It has also been proposed that OSA is one of the manifestations of the so-called metabolic syndrome [28]. Inflammation and metabolic aberrations are independently associated with many of the outcomes examined in OSA (i.e. sleepiness, fatigue and cardiometabolic disorders). We should note that preclinical markers of cardiometabolic disease, such as visceral adiposity, inflammation and insulin resistance, have not been measured or taken into account in any cross-sectional or prospective study to control for the net effect of the apnoeas/hypopneas.

In conclusion, the study by Arnardottir et al. [1] adds to the evidence that cast doubt on the utility of the currently recommended cut-offs for treatment of OSA (AHI  ≥15), even in the absence of any clinical problems (ICSD-3, DSM-V). Certainly, these cut-offs are inappropriate for older men and women as well as asymptomatic patients. In fact, the widely used, cumbersome mechanical treatments, such as positive airway pressure, may not be useful in this population. Longitudinal studies assessing the risk of OSA in the presence of comorbid conditions and the use of preclinical biological markers, such as inflammation markers, may help us to define who of the individuals with moderate, “silent” OSA need protective interventions. Finally, from a therapeutic standpoint, the elimination of AHI should not be our only concern. Rather, addressing modifiable risk factors associated with OSA and cardiometabolic health, such as obesity, exercise and mood, may narrow the grey area for practising clinicians.

Footnotes

  • Conflict of interest: None declared.

  • Received November 23, 2015.
  • Accepted November 27, 2015.
  • Copyright ©ERS 2016

References

  1. ↵
    1. Arnardottir ES,
    2. Bjornsdottir E,
    3. Olafsdottir KA, et al.
    Obstructive sleep apnoea in the general population: highly prevalent but minimal symptoms. Eur Respir J 2016; 47: 194–202.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Bixler EO,
    2. Vgontzas AN,
    3. Ten Have T, et al.
    Effects of age on sleep apnea in men. I. Prevalence and severity. Am J Respir Crit Care Med 1998; 157: 144–148.
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    1. Bixler EO,
    2. Vgontzas AN,
    3. Lin HM, et al.
    Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med 2001; 163: 608–613.
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    1. Bixler EO,
    2. Vgontzas AN,
    3. Lin H-M, et al.
    Association of hypertension and sleep disordered breathing. Arch Intern Med 2000; 160: 2289–2295.
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    1. Young T,
    2. Finn L,
    3. Peppard PE, et al.
    Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin Sleep Cohort. Sleep 2008; 31: 1071–1078.
    OpenUrlPubMedWeb of Science
  6. ↵
    1. Punjabi NM,
    2. Caffo BS,
    3. Goodwin JL, et al.
    Sleep-disordered breathing and mortality: a prospective cohort study. PLOS 2009; 6: e1000132.
    OpenUrlCrossRef
  7. ↵
    1. Lavie P,
    2. Lavie L
    . Unexpected survival advantage in elderly people with moderate sleep apnoea. J Sleep Res 2009; 18: 397–403.
    OpenUrlCrossRefPubMedWeb of Science
  8. ↵
    1. Marin JM,
    2. Carrizo S,
    3. Vicente E, et al.
    Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365: 1045–1053.
    OpenUrl
  9. ↵
    1. Redline S,
    2. Yenokyan G,
    3. Gottlieb DJ, et al.
    Obstructive sleep apnea–hypopnea and incident stroke: the Sleep Heart Health Study. Am J Respir Crit Care Med 2010; 182: 269–277.
    OpenUrlCrossRefPubMedWeb of Science
  10. ↵
    1. Arzt M,
    2. Young T,
    3. Finn L, et al.
    Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med 2005; 172: 1447–1451.
    OpenUrlCrossRefPubMedWeb of Science
  11. ↵
    1. Gottlieb DJ,
    2. Yenokyan G,
    3. Newman AB, et al.
    Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the Sleep Heart Health Study. Circulation 2010; 122: 352–360.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Reichmuth KJ,
    2. Austin D,
    3. Skatrud JB, et al.
    Association of sleep apnea and type II diabetes: a population-based study. Am J Respir Crit Care Med 2005; 172: 1590–1595.
    OpenUrlCrossRefPubMedWeb of Science
  13. ↵
    1. Peppard PE,
    2. Young T,
    3. Palta M, et al.
    Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342: 1378–1384.
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    1. Gunnarsson SI,
    2. Peppard PE,
    3. Korcarz CE, et al.
    Minimal nocturnal oxygen saturation predicts future subclinical carotid atherosclerosis: the Wisconsin Sleep Cohort. J Sleep Res 2015; 24: 680–686.
    OpenUrlCrossRefPubMed
  15. ↵
    1. Jullian-Desayes I,
    2. Joyeux-Faure M,
    3. Tamisier R, et al.
    Impact of obstructive sleep apnea treatment by continuous positive airway pressure on cardiometabolic biomarkers: a systematic review from sham CPAP randomized controlled trials. Sleep Med Rev 2015; 21: 23–38.
    OpenUrlCrossRefPubMed
    1. Vgontzas A,
    2. Zoumakis E,
    3. Bixler EO, et al.
    Selective effects of CPAP on sleep apnoea-associated manifestations. Eur J Clin Invest 2008; 38: 585–595.
    OpenUrlCrossRefPubMedWeb of Science
  16. ↵
    1. Kritikou I,
    2. Basta M,
    3. Vgontzas AN, et al.
    Sleep apnea, sleepiness, inflammation, and insulin resistance in middle-aged males and females. Eur Respir J 2014; 43: 145–155.
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Young T,
    2. Palta M,
    3. Dempsey J, et al.
    The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328: 1230–1235.
    OpenUrlCrossRefPubMedWeb of Science
  18. ↵
    1. Bixler EO,
    2. Vgontzas AN,
    3. Lin HM, et al.
    Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. J Clin Endocrinol Metab 2005; 90: 4510–4515.
    OpenUrlCrossRefPubMedWeb of Science
  19. ↵
    1. Kapur VK,
    2. Baldwin CM,
    3. Resnick HE, et al.
    Sleepiness in patients with moderate to devere sleep-disordered breathing. Sleep 2005; 28: 472–477.
    OpenUrlPubMedWeb of Science
  20. ↵
    1. Vgontzas AN,
    2. Bixler EO,
    3. Tan TL, et al.
    Obesity without sleep apnea is associated with daytime sleepiness. Arch Intern Med 1998; 158: 1333–1337.
    OpenUrlCrossRefPubMedWeb of Science
  21. ↵
    1. Fernandez-Mendoza J,
    2. Vgontzas AN,
    3. Kritikou I, et al.
    Natural history of excessive daytime sleepiness: role of obesity, weight loss, depression and sleep propensity. Sleep 2015; 38: 351–360.
    OpenUrlPubMed
  22. ↵
    1. Young T,
    2. Rabago D,
    3. Zgierska A, et al.
    Objective and subjective sleep quality in premenopausal, perimenopausal, and postmenopausal women in the Wisconsin Sleep Cohort Study. Sleep 2003; 26: 667–672.
    OpenUrlPubMedWeb of Science
  23. ↵
    1. Shahar E,
    2. Redline S,
    3. Young T, et al.
    Hormone replacement therapy and sleep-disordered breathing. Am J Respir Crit Care Med 2003; 167: 1186–1192.
    OpenUrlCrossRefPubMedWeb of Science
  24. ↵
    1. Margolis KL,
    2. Bonds DE,
    3. Rodabough RJ, et al.
    Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia 2004; 47: 1175–1187.
    OpenUrlPubMedWeb of Science
  25. ↵
    1. Vgontzas AN,
    2. Legro RS,
    3. Bixler EO, et al.
    Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 2001; 86: 517–520.
    OpenUrlCrossRefPubMedWeb of Science
  26. ↵
    1. Tasali E,
    2. Van Cauter E,
    3. Ehrmann DA
    . Relationships between sleep disordered breathing and glucose metabolism in polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 36–42.
    OpenUrlCrossRefPubMedWeb of Science
  27. ↵
    1. Vgontzas AN,
    2. Bixler EO,
    3. Chrousos GP
    . Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 2005; 9: 211–214.
    OpenUrlCrossRefPubMedWeb of Science
PreviousNext
Back to top
View this article with LENS
Vol 47 Issue 1 Table of Contents
European Respiratory Journal: 47 (1)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Moderate sleep apnoea: a “silent” disorder, or not a disorder at all?
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Moderate sleep apnoea: a “silent” disorder, or not a disorder at all?
Edward O. Bixler, Alexandros N. Vgontzas, Jordan Gaines, Julio Fernandez-Mendoza, Susan L. Calhoun, Duanping Liao
European Respiratory Journal Jan 2016, 47 (1) 23-26; DOI: 10.1183/13993003.01955-2015

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Moderate sleep apnoea: a “silent” disorder, or not a disorder at all?
Edward O. Bixler, Alexandros N. Vgontzas, Jordan Gaines, Julio Fernandez-Mendoza, Susan L. Calhoun, Duanping Liao
European Respiratory Journal Jan 2016, 47 (1) 23-26; DOI: 10.1183/13993003.01955-2015
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Subjects

  • Sleep medicine
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • A step forward for an intermediate cystic fibrosis population
  • Predicting pulmonary hypertension using echocardiography
  • We need to understand why viral infections lead to acute asthma
Show more Editorials

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Reviewers
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2022 by the European Respiratory Society