Editor's Note: Commentary based on Chirinos JA, Gurubhagavatula I, Teff K, et al. CPAP, Weight Loss, or Both for Obstructive Sleep Apnea. N Engl J Med 2014;370:2265-75.

Background:

The association of obesity and obstructive sleep apnea is well established. Both conditions are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear.

Methods:

181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter were randomly assigned to receive treatment with either continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. The incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure was assessed.

Results:

Follow-up data was available on 146 participants. A reduction in CRP levels, insulin resistance, and serum triglyceride levels was noticed in those assigned to weight loss only and to the combined interventions, but not in the group receiving CPAP alone. There was no significant incremental effect on CRP levels was found for the combined interventions. The reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. Blood pressure was reduced in all three groups, with more reduction in the combined interventions than either CPAP or weight loss alone.

Conclusion:

In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention and weight loss result in incremental reduction in insulin resistance, serum triglyceride levels more than CPAP. The combined intervention was associated with more reduction in blood pressure than either intervention alone, while CRP levels were not significantly different among all interventions.

Commentary/Perspective:

Obstructive sleep apnea (OSA) is associated with increased incidence of many pro-atherosclerotic risk factors, including insulin resistance, dyslipidemia, hypertension, and inflammation.^1-3 Similarly obesity is also associated with insulin resistance, dyslipidemia, hypertension, and inflammation.^4,5 OSA and obesity had a very complex and bidirectional relationship. Although both are associated with pro-atherosclerotic risk factors, the causality relationship is not well established.^6-8

Weight loss is known to significantly reduce CRP levels, insulin resistance, dyslipidemia, and blood pressure.^9-11 In contrast, many studies show conflicting results in regard of the impact of CPAP therapy on CRP level, insulin sensitivity, or dyslipidemia.^12-17

This study is very important, as it provides randomized prospective data comparing the effect of either weight loss or CPAP with a combination of both. This study showed that adding CPAP therapy to a weight-loss intervention did not have a significant incremental effect on CRP levels, as compared with either intervention alone. On the other hand, the combined intervention had an incremental effect on insulin resistance and serum triglyceride levels, as compared with CPAP alone, but not with weight loss alone. The impact of the combined interventions on blood pressure showed a larger reduction in blood pressure when compared to either therapy alone.¹⁸

However, this study had multiple limitations. First, it did not include a sham CPAP intervention as an alternative control to CPAP. But this can be justified by studies showing that both sham CPAP and the absence of treatment for OSA are considered to be adequate controls for an active CPAP intervention. Second, this trial did not include any group in which no therapy was implemented because of ethical considerations. Third, the time frame of 24 weeks used for the trial may be short in show a potential impact of CPAP on insulin resistance and lipid profile. Finally, the study excluded patients with diabetes and mild OSA, so our findings cannot be extended to these patients' subgroups.

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References

1. Ip MS, Lam B, Ng MM, et al. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002;165:670-6.
2. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000;283:1829-36.
3. Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 2002;105:2462-4.
4. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007;116:39-48.
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9. Horvath K, Jeitler K, Siering U, et al. Long-term effects of weight-reducing interventions in hypertensive patients: systematic review and meta-analysis. Arch Intern Med 2008;168:571-80.
10. Samaha FF, Iqbal N, Seshadri P, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 2003;348:2074-81.
11. Nicklas BJ, Ambrosius W, Messier SP, et al. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am J Clin Nutr 2004;79:544-51.
12. Ishida K, Kato M, Kato Y, et al. Appropriate use of nasal continuous positive airway pressure decreases elevated C-reactive protein in patients with obstructive sleep apnea. Chest 2009;136:125-9.
13. Patruno V, Aiolfi S, Costantino G, et al. Fixed and autoadjusting continuous positive airway pressure treatments are not similar in reducing cardiovascular risk factors in patients with obstructive sleep apnea. Chest 2007;131:1393-9.
14. Akashiba T, Akahoshi T, Kawahara S, et al. Effects of long-term nasal continuous positive airway pressure on C-reactive protein in patients with obstructive sleep apnea syndrome. Intern Med 2005;44:899-900.
15. Yang D, Liu Z, Yang H, Luo Q. Effects of continuous positive airway pressure on glycemic control and insulin resistance in patients with obstructive sleep apnea: a meta-analysis. Sleep Breath 2013;17:33-8.
16. Coughlin SR, Mawdsley L, Mugarza JA, et al. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J 2007;29:720-7.
17. Craig SE, Kohler M, Nicoll D, et al. Continuous positive airway pressure improves sleepiness but not calculated vascular risk in patients with minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised controlled trial. Thorax. 2012;67:1090-6.
18. Chirinos JA, Gurubhagavatula I, Teff K, et al. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 2014;370:2265-75.

Keywords: Blood Pressure, Blood Pressure Determination, Insulin Resistance, Obesity, Sleep Apnea, Obstructive, Triglycerides, Weight Loss

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