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Eur Respir J 2008; 31:223-225
Copyright ©ERS Journals Ltd 2008

Cardiovascular and metabolic effects of CPAP in obese obstructive sleep apnoea patients

S. Teramoto1, Y. Yamaguchi1, H. Yamamoto1, Y. Hanaoka1, M. Ishii1, S. Hibi1, T. Ishii1, H. Kume2 and Y. Ouchi1

Depts of 1 Geriatric Medicine, and 2 Urology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

To the Editors:

In a recent issue of the European Respiratory Journal, Coughlin et al. 1 demonstrated that, in Caucasians with untreated obstructive sleep apnoea (OSA), continuous positive airway pressure (CPAP) can improve baroreceptor responsiveness and reduce waking blood pressure within 6 weeks, but that this treatment period was insufficient to modify insulin resistance or change the metabolic profile. This is the first randomised placebo-controlled blinded crossover trial comparing cardiovascular and metabolic outcomes after 6 weeks of therapeutic and sham CPAP in obese symptomatic Caucasians with OSA. We have found similar CPAP effects in obese Japanese OSA patients (table 1Go). The authors suggested that there is a need to offer multiple modalities of treatment to obese OSA patients if their cardiovascular risk profile is to be successfully modified. We totally agree with their conclusion. However, it may be necessary to address the following unresolved issues.


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  		Table 1— Effect of 6-week continuous positive airway pressure (CPAP) treatment on components of metabolic syndrome in obstructive sleep apnoea (OSA)

 
1) Although the participating OSA subjects were randomised to receive either therapeutic or identical sham CPAP, sham CPAP may not be the best placebo treatment. Although therapeutic CPAP improves sleep quality in OSA patients, sham CPAP may not always improve sleep quality and daytime function in patients 2. Healthy individuals without OSA may experience night-time CPAP as a form of torture. However, patients with severe OSA have a good night’s sleep with CPAP.

2) The severity of the OSA may influence the effect of CPAP on metabolic outcomes. As shown in table 1Go, CPAP treatment exerted significant effects on some metabolic variables in very severe OSA (apnoea/hypopnoea index (AHI) >45 events·h–1), but not in moderate-to-severe OSA (AHI <45 events·h–1).

3) There is an effect of sex on metabolic outcomes and sleep apnoeas 3. Risk factors for metabolic syndrome also differed by sex; in males, age, body mass index (BMI) and OSA (AHI ≥15 events·h–1) were significantly associated with metabolic syndrome, whereas in females, BMI was the only risk factor 4.

4) The effect of short-term withdrawal of CPAP therapy on cardiovascular and metabolic variables may be of interest in OSA patients. This inverse method may also confirm the randomised placebo-controlled blinded crossover trial results. It was recently reported that 1 week of CPAP withdrawal is associated with a return of OSA and a marked increase in sympathetic activity without concomitant elevation of vascular inflammatory marker levels 5. Therefore, effects of CPAP treatment and its withdrawal may differ between cardiovascular function and metabolic and inflammatory function as a function of time.

5) The relationships between metabolic variables and systemic inflammation and sympathetic activity are complex 6. There is a positive correlation between interleukin (IL)-6 or tumour necrosis factor (TNF)-{alpha} plasma levels and BMI. IL-6, TNF-{alpha} and insulin levels are elevated in sleep apnoea independently of obesity and visceral fat 7, 8. Conversely, recent data suggest that OSA has no independent association with lipid abnormalities, insulin resistance, and serum leptin and adiponectin levels. On multivariate analysis, obesity was the major determinant of metabolic abnormalities 9.

Furthermore, there is a maladaptive autonomic response of chemoreceptors, reacting to the hypoxia, hypercapnia and acidosis of sleep apnoea in OSA patients. The elevated sympathetic response triggers an inflammatory cascade that results in a myriad of downstream consequences, including insulin resistance, hypertension, diabetes, atherosclerosis and metabolic syndrome. The sympathetic bias and endocrine disturbances may further exacerbate sleep disturbance in a potentially pernicious cycle.

6) Poor compliance with CPAP may considerably affect metabolic outcomes 10. Unfortunately, compliance with CPAP was generally very low in the population-based sample. Furthermore, the patients with more severe OSA may show greater CPAP use than those with mild-to-moderate OSA. Both compliance with CPAP and patient selection may have affected the results of the current study.

Even though we totally agree with the main results of the study by Coughlin et al. 1, changes in cardiovascular and metabolic variables following CPAP treatment may differ. Although more detailed results from a broad-ranging population with OSA are needed, OSA and its related metabolic abnormalities should be treated by means of CPAP and other useful modalities, including statins, angiotensin II receptor blockers, etc.

We believe that continuous positive airway pressure treatment is effective at reducing cardiovascular events through reduced blood pressure, decreased sympathetic activity and reduced systemic inflammation 10. However, the relative contributions to the reduction in cardiovascular events should be further elucidated in terms of obstructive sleep apnoea severity and the basic mechanisms of metabolic syndrome.

REFERENCES

  1. Coughlin SR, Mawdsley L, Mugarza JA, Wilding JP, Calverley PM. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J 2007;29:720–727.[Abstract/Free Full Text]
  2. Teramoto S, Ohga E, Ouchi Y. Obstructive sleep apnoea. Lancet 1999;354:1213–1214.[Web of Science][Medline] [Order article via Infotrieve]
  3. Teramoto S, Kume H, Yamaguchi Y, et al. Improvement of endothelial function with allopurinol may occur in selected patients with OSA: effect of age and sex. Eur Respir J 2007;29:216–217.[Free Full Text]
  4. Sasanabe R, Banno K, Otake K, et al. Metabolic syndrome in Japanese patients with obstructive sleep apnoea syndrome. Hypertens Res 2006;29:315–322.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  5. Phillips CL, Yang Q, Williams A, et al. The effect of short-term withdrawal from continuous positive airway pressure therapy on sympathetic activity and markers of vascular inflammation in subjects with obstructive sleep apnoea. J Sleep Res 2007;16:217–225.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  6. Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnoea is a manifestation of the metabolic syndrome. Sleep Med Rev 2005;9:211–224.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  7. Teramoto S, Yamamoto H, Yamaguchi Y, Namba R, Ouchi Y. Obstructive sleep apnoea causes systemic inflammation and metabolic syndrome. Chest 2005;127:1074–1075.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  8. Teramoto S, Yamamoto H, Ouchi Y. Increased C-reactive protein and increased plasma interleukin-6 may synergistically affect the progression of coronary atherosclerosis in obstructive sleep apnoea syndrome. Circulation 2003;107:E40–0.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  9. Sharma SK, Kumpawat S, Goel A, Banga A, Ramakrishnan L, Chaturvedi P. Obesity, and not obstructive sleep apnoea, is responsible for metabolic abnormalities in a cohort with sleep-disordered breathing. Sleep Med 2007;8:12–17.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  10. Lindberg E, Berne C, Elmasry A, Hedner J, Janson C. CPAP treatment of a population-based sample – what are the benefits and the treatment compliance?. Sleep Med 2006;7:553–560.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]




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