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Pro: should asymptomatic patients with moderate-to-severe OSA be treated?

Silke Ryan
Breathe 2019 15: 7-10; DOI: 10.1183/20734735.0340-2018
Silke Ryan
1Pulmonary and Sleep Disorders Unit, St. Vincent's University Hospital, Dublin, Ireland
2School of Medicine, The Conway Institute, University College Dublin, Dublin, Ireland
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Abstract

Substantial evidence points to a benefit with CPAP on cardiovascular and metabolic outcomes in asymptomatic patients with moderate-to-severe obstructive sleep apnoea http://ow.ly/FUxN30nkTqU

Obstructive sleep apnoea (OSA) is a highly prevalent condition representing a major global public health burden [1]. Attributed to the prominent symptom of excessive daytime sleepiness, it leads to significant impairments in quality of life, cognitive performance and social functioning and to a dramatic increase in road traffic and occupational accidents [2]. However, the major health burden in OSA patients is due to the significant association with cardiovascular and metabolic diseases, such as systemic arterial hypertension, coronary artery disease, heart failure, stroke or type 2 diabetes leading to substantial morbidity and mortality [3, 4]. Continuous positive airway pressure (CPAP) therapy which acts to splint the upper airway open during sleep is the treatment of choice, particularly for patients with moderate or severe disease. CPAP often has a dramatic effect on a patient's awake performance. It improves objective and subjective sleepiness, quality of life, neurocognitive function and driving performance [5]. The question of whether CPAP therapy should be extended to patients who have moderate or severe OSA but who are asymptomatic, i.e. do not complain of excessive daytime sleepiness, remains a subject of great debate. Importantly, the term “asymptomatic” is frequently misleading. Subjects with OSA may under-report their level of sleepiness, potentially motivated by concerns in relation to a compromise in their professional activities or driving licensing [6]. Furthermore, patients are often accustomed to their symptoms and only realise the impact of their OSA on their quality of life after treatment initiation [7]. The Epworth sleepiness scale (ESS) is the most widely used tool to assess sleepiness; however, it correlates poorly with objective measures of sleepiness and is widely open to reporting bias. Many studies have used a cut-off value of 10 to distinguish sleepy from non-sleepy subjects, however this cut-off is a very arbitrary value with poor sensitivity and specificity [8]. Despite these concerns, there is truly a considerable proportion of moderate or severe OSA patients who exhibit no significant daytime symptoms. The treatment decision in those cases is closely linked to a potential benefit of CPAP therapy on cardiometabolic outcomes. While large observational studies lend support for a positive impact of CPAP on cardiometabolic consequences, this has recently been challenged, in particular by the SAVE trial, a large randomised controlled secondary prevention study which did not reveal a benefit with CPAP therapy in comparison to standard care [9, 10]. But are these data sufficient enough to withhold CPAP therapy in non-sleepy subjects who have moderate-to-severe OSA? The answer is clearly “no”.

First, interpretation of the results of the SAVE study must be made with caution. The main limitation of the study was the suboptimal compliance of only 3.3 h per night with CPAP therapy. In support of the crucial role of CPAP adherence, the RICCADSA randomised controlled trial, which included OSA patients with coronary artery disease and an ESS <10, identified a significant reduction in cardiovascular risk once data were adjusted for CPAP compliance (>4 h per night) [11]. A similar conclusion has been drawn from a Spanish multicentre randomised controlled trial investigating the impact of CPAP on the combined primary end-point of hypertension incidence and cardiovascular events in asymptomatic OSA patients [12]. While the intention-to-treat analysis revealed no difference to standard care, a significant benefit became evident when adherence (defined as usage of >4 h per night) was taken into account. Two recent meta-analyses support the beneficial value of adherent CPAP therapy in non-sleepy subjects [13, 14]. Thus, CPAP therapy in this group probably leads to a favourable outcome, but adequate compliance needs to be guaranteed. It is noteworthy that CPAP therapy is feasible in these patients and with adequate support and education, particularly in the initial phase of therapy, similar acceptance rates to sleepy OSA patients can be achieved [15].

Secondly, while many studies have focused on cardiovascular events in patients with established cardiac diseases, there is also a growing body of evidence of a positive impact of CPAP on the early stages of cardiovascular or metabolic diseases. This is particularly true for endothelial dysfunction, an early and key event in the process of atherosclerosis. Several randomised and non-randomised studies have demonstrated a significant improvement in endothelial function with CPAP therapy [16]. This favourable outcome also extends to subjects without daytime sleepiness, as demonstrated by results of the MOSAIC study evaluating the effect of CPAP therapy versus standard care over a 6-month period in minimally symptomatic patients (mean ESS of 8) [17]. Furthermore, CPAP therapy may also influence the development of hypertension in OSA. In the Wisconsin Sleep Cohort Study, OSA emerged as an independent risk factor for incident hypertension and these results were reproduced in a large, prospective sleep cohort study from Spain, but moreover, effective CPAP therapy significantly lowered the risk in comparison to untreated OSA subjects [18, 19]. Importantly, hypertension in OSA has several characteristic features. A non-dipping nocturnal blood pressure profile, defined as a less than 10% drop in blood pressure at night, is particularly likely in patients with OSA and is an independent prognostic marker for cardiovascular events in hypertensive and normotensive populations as reported in general and OSA cohorts [20, 21]. In support of a key role of CPAP therapy in the early stage of the development of hypertension, our group has recently demonstrated that effective CPAP therapy leads to a significant recovery of the nocturnal blood pressure pattern in normotensive OSA subjects (unpublished data), in keeping with data from a different group [22], and thus, potentially prevents the development of hypertension and subsequent cardiovascular events. In addition, CPAP may also impact on conditions affecting glucose metabolism. Over the past few years there has been fast growing evidence of the association of OSA with insulin resistance, which often pre-dates type 2 diabetes. Experimental studies have provided substantial insight into the underlying pathogenesis demonstrating the key role of intermittent hypoxia as the hallmark feature of OSA in this process [23]. Several randomised controlled trials evaluating the effect of CPAP on insulin resistance have been performed and have yielded differing results. However, the methodology of these studies varied significantly in terms of subject numbers, duration of treatment and compliance with CPAP. Treatment seems most beneficial in less obese subjects, and overall, meta-analyses have shown a favourable effect on insulin resistance [24, 25]. In summary, and in the absence of a definitive primary prevention trial which is an unrealistic goal in the field, the available data provide currently the best evidence of a widespread benefit of CPAP therapy in the prevention of early cardiovascular and metabolic diseases; however, it remains poorly understood at this stage if these benefits extend to asymptomatic patients.

Thirdly, it is increasingly recognised that a treatment response to CPAP cannot be universally expected and this variability may have contributed to the negative overall results obtained by some studies. The reasons for the lack of response in some patients are as yet unknown. However, the highly variable duration of untreated OSA prior to presentation probably plays an important role. The precise onset of the disease usually remains speculative but probably pre-dates the diagnosis from a few weeks to often several years. Plausibly, there is a dose–dependent relationship between the duration of OSA and cardiometabolic disease processes which will in turn influence the effectiveness of CPAP treatment on such outcomes. This point, which is unfortunately widely ignored, has been supported by several experimental studies demonstrating that the detrimental effects of intermittent hypoxia, the main pathophysiological triggering factor in OSA, may not be reversible even with prolonged periods of normoxic recovery [26, 27]. In addition, the magnitude of the effect of CPAP is substantially modified by other factors such as dietary measures, physical activity or pharmacological treatments. For example, Chirinos et al. [28] identified an incremental improvement in insulin resistance, serum triglycerides and blood pressure when CPAP therapy was combined with a weight loss regimen as compared with either intervention alone. Furthermore, Pepin et al. [29] reported a significant additive benefit on blood pressure control when CPAP was combined with the anti-hypertensive drug Valsartan. Thus, treatment of patients with moderate-to-severe OSA should, beside CPAP therapy, also include effective lifestyle modifications and management of other cardiometabolic risk factors in order to obtain the maximum value.

In conclusion, there is substantial support of a beneficial role of CPAP on various cardiovascular and metabolic processes, and these benefits probably extend to asymptomatic patients, providing assurance of adequate compliance. However, without a doubt there are differences in the magnitude of individual responses to CPAP and hence, future studies will need to focus on the identification of those who respond versus those who fail using a personalised approach but with careful consideration of the wide spectrum of adverse outcomes. In the absence of such knowledge, CPAP therapy should be offered to asymptomatic subjects with moderate-to-severe OSA. As physicians working in the field, we are in a great position to offer a treatment which can effectively control a condition without causing significant risks and harms. CPAP therapy has transformed the lives of many of our patients and with no equally efficient treatment on the horizon will continue to do so. However, it should be embedded in a multidisciplinary management of OSA patients in conjunction with lifestyle measures and optimal pharmaceutical treatments for comorbid conditions.

Footnotes

  • Conflict of interest: S. Ryan has nothing to disclose.

  • Copyright ©ERS 2019

Breathe articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

References

  1. ↵
    1. Peppard PE,
    2. Young T,
    3. Barnet JH, et al.
    Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 2013; 177: 1006–1014.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Mulgrew AT,
    2. Nasvadi G,
    3. Butt A, et al.
    Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea. Thorax 2008; 63: 536–541.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Kent BD,
    2. Grote L,
    3. Ryan S, et al.
    Diabetes mellitus prevalence and control in sleep-disordered breathing: the European Sleep Apnea Cohort (ESADA) study. Chest 2014; 146: 982–990.
    OpenUrlCrossRefPubMed
  4. ↵
    1. McNicholas WT,
    2. Bonsignore MR
    . Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J 2007; 29: 156–178.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Gordon P,
    2. Sanders MH
    . Sleep.7: positive airway pressure therapy for obstructive sleep apnoea/hypopnoea syndrome. Thorax 2005; 60: 68–75.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Strohl KP,
    2. Brown DB,
    3. Collop N, et al.
    An official American Thoracic Society Clinical Practice Guideline: sleep apnea, sleepiness, and driving risk in noncommercial drivers. An update of a 1994 Statement. Am J Respir Crit Care Med 2013; 187: 1259–1266.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Leclerc G,
    2. Lacasse Y,
    3. Page D, et al.
    Do obstructive sleep apnea syndrome patients underestimate their daytime symptoms before continuous positive airway pressure treatment? Can Respir J 2014; 21: 216–220.
    OpenUrl
  8. ↵
    1. Chervin RD,
    2. Aldrich MS
    . The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea. Neurology 1999; 52: 125–131.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Marin JM,
    2. Carrizo SJ,
    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: 1046–1053.
    OpenUrlCrossRefPubMed
  10. ↵
    1. McEvoy RD,
    2. Antic NA,
    3. Heeley E, et al.
    CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 2016; 375: 919–931.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Peker Y,
    2. Glantz H,
    3. Eulenburg C, et al.
    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.
    OpenUrlPubMed
  12. ↵
    1. Barbe F,
    2. Duran-Cantolla J,
    3. Sanchez-de-la-Torre M, et al.
    Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA 2012; 307: 2161–2168.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Abuzaid AS,
    2. Al Ashry HS,
    3. Elbadawi A, et al.
    Meta-analysis of cardiovascular outcomes with continuous positive airway pressure therapy in patients with obstructive sleep apnea. Am J Cardiol 2017; 120: 693–699.
    OpenUrl
  14. ↵
    1. Bratton DJ,
    2. Stradling JR,
    3. Barbe F, et al.
    Effect of CPAP on blood pressure in patients with minimally symptomatic obstructive sleep apnoea: a meta-analysis using individual patient data from four randomised controlled trials. Thorax 2014; 69: 1128–1135.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Campos-Rodriguez F,
    2. Martinez-Alonso M,
    3. Sanchez-de-la-Torre M, et al.
    Long-term adherence to continuous positive airway pressure therapy in non-sleepy sleep apnea patients. Sleep Med 2016; 17: 1–6.
    OpenUrl
  16. ↵
    1. Schwarz EI,
    2. Puhan MA,
    3. Schlatzer C, et al.
    Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: a systematic review and meta-analysis. Respirology 2015; 20: 889–895.
    OpenUrl
  17. ↵
    1. Kohler M,
    2. Craig S,
    3. Pepperell JCT, et al.
    CPAP improves endothelial function in patients with minimally symptomatic OSA: results from a subset study of the MOSAIC trial. Chest 2013; 144: 896–902.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Marin JM,
    2. Agusti A,
    3. Villar I, et al.
    Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 2012; 307: 2169–2176.
    OpenUrlCrossRefPubMed
  19. ↵
    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.
    OpenUrlCrossRefPubMed
  20. ↵
    1. Boggia J,
    2. Li Y,
    3. Thijs L, et al.
    Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet 2007; 370: 1219–1229.
    OpenUrlCrossRefPubMed
  21. ↵
    1. Sasaki N,
    2. Ozono R,
    3. Edahiro Y, et al.
    Impact of non-dipping on cardiovascular outcomes in patients with obstructive sleep apnea syndrome. Clin Exp Hypertens 2015; 37: 449–453.
    OpenUrl
  22. ↵
    1. Sapina-Beltran E,
    2. Santamaria-Martos F,
    3. Benitez I, et al.
    Normotensive patients with obstructive sleep apnoea: changes in 24-h ambulatory blood pressure monitoring with continuous positive airway pressure treatment. J Hypertens 2018; in press [https://doi.org/10.1097/HJH.0000000000001934].
  23. ↵
    1. Murphy AM,
    2. Thomas A,
    3. Crinion SJ, et al.
    Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation. Eur Respir J 2017; 49: 1601731.
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Iftikhar IH,
    2. Hoyos CM,
    3. Phillips CL, et al.
    Meta-analyses of the association of sleep apnea with insulin resistance, and the effects of CPAP on HOMA-IR, adiponectin, and visceral adipose fat. J Clin Sleep Med 2015; 11: 475–485.
    OpenUrlPubMed
  25. ↵
    1. Yang D,
    2. Liu Z,
    3. Yang H
    . The impact of effective continuous positive airway pressure on homeostasis model assessment insulin resistance in non-diabetic patients with moderate to severe obstructive sleep apnea. Diabetes Metab Res Rev 2012; 28: 499–504.
    OpenUrlPubMed
  26. ↵
    1. Gileles-Hillel A,
    2. Almendros I,
    3. Khalyfa A, et al.
    Prolonged exposures to intermittent hypoxia promote visceral white adipose tissue inflammation in a murine model of severe sleep apnea: effect of normoxic recovery. Sleep 2017; 40: zsw074.
    OpenUrl
  27. ↵
    1. Polak J,
    2. Shimoda LA,
    3. Drager LF, et al.
    Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure. Sleep 2013; 36: 1483–1490.
    OpenUrlCrossRefPubMed
  28. ↵
    1. Chirinos JA,
    2. Gurubhagavatula I,
    3. Teff K, et al.
    CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 2014; 370: 2265–2275.
    OpenUrlCrossRefPubMed
  29. ↵
    1. Pepin JL,
    2. Tamisier R,
    3. Barone-Rochette G, et al.
    Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med 2010; 182: 954–960.
    OpenUrlCrossRefPubMed
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Silke Ryan
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