Elsevier

Sleep Medicine Reviews

Volume 18, Issue 1, February 2014, Pages 49-59
Sleep Medicine Reviews

Clinical review
Untreated obstructive sleep apnea and the risk for serious long-term adverse outcomes: A systematic review

https://doi.org/10.1016/j.smrv.2013.01.003Get rights and content

Summary

Background

Reports on the association between obstructive sleep apnea (OSA) and risk of death, cardiovascular (CV) events, diabetes and depression have been inconsistent.

Methods

We conducted a systematic review of the prognostic value of clinical and polysomnographic (PSG) characteristics of OSA for adverse long-term outcomes of untreated OSA in adult patients. A comprehensive search strategy for prognosis studies, OSA, CV events, mortality, depression and diabetes was developed in collaboration with a medical information specialist. All English language studies, from Jan 1999 to Dec 2011, with longitudinal design in adults with OSA diagnosed by PSG recording, found through Medline, Embase and bibliographies of identified articles, were considered eligible. Quality was assessed using published guidelines.

Results

Among 26 articles, ten evaluated the association of OSA with mortality, 9 with a composite CV outcome, 4 with stroke, 2 with diabetes and 1 with depression. Significant relationships between the apnea–hypopnea index (AHI) and outcomes of interest were reported in 18 studies: seven for all-cause mortality, six for composite CV events, three for stroke, one for diabetes and one for depression. The effect of AHI was attenuated by female gender, older age, absence of daytime sleepiness and higher body mass index. Due to clinical heterogeneity between studies, meta-analyses were not performed.

Conclusion

Evidence exists in men for a relationship between OSA and all-cause mortality and a composite CV outcome. Associations between OSA and other outcomes remain uncertain. Among OSA-specific markers, only AHI was a consistent predictor. Other consistent predictors were traditional CV risk factors. Research is required to identify effect modifiers and the predictive ability of various AHI threshold values and hypopnea definitions. An enhanced set of OSA-specific predictors will allow better risk stratification to guide OSA treatment.

Introduction

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by repeated episodes of upper airway obstruction during sleep.1 It affects an estimated 9% of women and 24% of men.2, 3

There are plausible biological pathways (through chronic intermittent hypoxemia, sleep fragmentation, hemodynamic disturbances and alterations in sympathetic activity) through which untreated OSA might lead to death, cardiovascular (CV) events, diabetes or depression (Fig. 1).4, 5, 6, 7, 8, *9 However, reports on the causal relationship between OSA and such sequelae have been inconsistent.10, 11, *12, 13, 14, 15, *16, 17, *18, 19, *20, 21, *22, 23 There is also little known about which specific clinical and physiological factors best predict the occurrence of these adverse outcomes in OSA.23 In addition, it is unknown if the thresholds for diagnosing and treating OSA should be the same in people with CV disease and those who are otherwise healthy,23 or if the presence of OSA changes the effect of traditional risk factors for CV events and mortality. We conducted a systematic review of untreated OSA in adult patients with two goals: a) to examine the relationship between OSA and death, CV events, diabetes and depression; and b) to determine the prognostic value of demographic, clinical and polysomnographic (PSG) characteristics of OSA on these long-term outcomes. Non-disease outcomes such as motor vehicle or occupational accidents, although important, were not examined in the current review.

Section snippets

Data sources and searches

In collaboration with disease experts and a medical information specialist, we developed a comprehensive search strategy for prognostic studies of OSA with outcomes of myocardial infarction (MI), stroke, mortality, depression and diabetes.24 All English language peer-reviewed studies published from Jan 1999 to Dec 2011 with prospective or retrospective data collection and a longitudinal design,25 found through Medline, Embase and bibliographies of identified articles and reviews, were

Literature search and quality assessment

Of 2547 articles identified, 49 were selected for full-text review and 32 were included (Fig. 2). Supplementary Table S2 shows reasons for exclusion of 17 studies.

Of the 32 studies (Table 1), 26 were assessed as having “Partly” or “No” on all bias criteria and were included in our main analyses. Six of these studies, carried out under the auspices of the Sleep Heart Health Study (SHHS) or Wisconsin Sleep Cohort, were high quality studies (“++”). Among the remaining 20 studies, five fulfilled

Discussion

We conducted a systematic review in order to investigate the relationship between OSA and death, CV events, diabetes and depression and determine the prognostic value of demographic, clinical and PSG characteristics of OSA on these outcomes. Of 32 articles evaluated, 26 at least partly addressed sources of potential study biases. All six studies classified as ‘high quality’ were based on two large seminal community-based cohort studies designed to evaluate the long-term consequences of OSA: the

Limitations

We acknowledge heterogeneity in the primary studies, which demonstrate a great deal of variation in the populations studied and definitions of OSA, AHI and the composite CV outcome.

The main concern regarding the community based studies, which were found to be “high quality”, is that severe OSA is underrepresented, with 341cases in 6294 subjects in the SHHS32 and 63 in 1522 in the WSCS.16 Similarly, none of the studies distinguished patients with OSA from those with obesity-hypoventilation

Conclusion

Evidence exists in men for a relationship between OSA and all-cause mortality and a composite CV outcome. Associations between OSA and other outcomes remain uncertain. Among OSA-specific markers, only AHI was a consistent predictor. Other consistent predictors were traditional CV risk factors. Research is required to identify effect modifiers and the predictive ability of various AHI threshold values and hypopnea definitions. An enhanced set of OSA-specific predictors will allow better risk

Conflict of interest statement

Our study had no external funding source. The first author, Dr. Tetyana Kendzerska is supported by 2011/2012 Ontario Graduate Scholarship, 2011/2012 Hunter Graduate Scholarship (the University of Toronto) and 2012/2013 Doctoral Research Award from the Canadian Institutes of Health Research. The authors have no conflict of interest to declare pertaining to this review.

Acknowledgments

We gratefully acknowledge Ms. Marina Englesakis, Information Specialist for Surgical Divisions, Neuroscience and Medical Education Health Sciences Library, University Health Network, Toronto General Hospital for her assistance with the literature search. We also appreciate help we received from the Office of English Language and Writing Support for graduate students at University of Toronto.

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