|Year : 2012 | Volume
| Issue : 2 | Page : 107-108
Metabolic abnormalities in obstructive sleep apnea: A double whammy
Manish Soneja1, Virendra Singh2
1 Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medicine, SMS Medical College, Jaipur, India
|Date of Web Publication||24-Apr-2012|
Department of Medicine, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Soneja M, Singh V. Metabolic abnormalities in obstructive sleep apnea: A double whammy. Lung India 2012;29:107-8
The global obesity epidemic continues to gain momentum, resulting in increased prevalence of obstructive sleep apnea (OSA). In India, a recent community-based survey reported prevalence of OSA as 9.3% and that of obstructive sleep apnea syndrome (OSAS) as 2.8%.  The figures are similar to those reported in western population.  These patients often have co-existent risk factors for cardiovascular disease such as obesity, hypertension, dyslipidemia, and impaired glucose tolerance. This clustering of risk factors is called metabolic syndrome. OSA has been shown to be independently associated with these risk factors including hypertension,  dyslipidemia,  and insulin resistance.  Coughlin et al. demonstrated that OSA is independently associated with metabolic syndrome.  The co-occurrence of OSA and metabolic syndrome, termed syndrome Z, acts synergistically to increase the risk for cardiovascular disease. The prevalence of syndrome Z in India ranges from 4.5% in population-based study  to 79% among patients with OSA in hospital-based study.  However, obesity acts as an important confounder in interpretation of the relationship between OSA and metabolic syndrome, due to its independent association with OSA and other cardiovascular risk factors.  These patients are frequently prescribed multiple drugs to address individual components of the metabolic syndrome.
Continuous positive airway pressure (CPAP) is the first-line treatment for symptomatic OSA. However, the effect of CPAP on the metabolic syndrome is unclear. The most consistent effect reported is the reduction in blood pressure with CPAP therapy. , It is also believed that pulmonary pressure elevation in sleep apnea patients usually settles down after initiation of CPAP treatment.  The reports on effect on insulin resistance , and lipid profile are discordant. , Two studies assessing the effect of CPAP on metabolic syndrome in patients with obstructive sleep apnea gave divergent results. , In a recent study by Sharma et al.,  published in the December 15 issue of the New England Journal of Medicine, CPAP therapy has been shown to be associated with improvement in various components of metabolic syndrome in patients with both OSA and metabolic syndrome. The authors of this study should be congratulated for giving convincing evidence in a double blind study design.
The study was a double-blind, placebo-controlled, randomized, crossover trial with 3 months of CPAP and 3 months of sham CPAP, and a 1-month washout period between the interventions. The crossover design obviated the need for a control group. Ninety patients with moderate to severe OSA and not on treatment for hypertension, diabetes mellitus, or dyslipidemia were randomized and 86 of them completed the study. The patients had a mean age of 45 years and all but 9 were males. Seventy-five of 86 patients (87%) had metabolic syndrome at the time of recruitment. At baseline, 47% of patients had hypertension, 49% had diabetes mellitus, and dyslipidemia was present in 84% of patients. The frequency of the metabolic syndrome decreased significantly after CPAP therapy as compared with sham CPAP. After CPAP therapy, 13% of the patients no longer met criteria for the metabolic syndrome compared to 1% of those with sham CPAP therapy. There was a significant reduction in systolic (3.9 mm Hg) and diastolic (2.5 mm Hg) blood pressure, glycated hemoglobin (0.2%), triglycerides (18.7 mg/dl), and low density lipoprotein (LDL) (9.6 mg/dl), non-HDL (13.3 mg/dl), and total cholesterol (13.3 mg/dl) as well as significant decrease in body mass index (BMI) and visceral and subcutaneous fat after CPAP therapy as compared with sham therapy. There was no effect on fasting blood glucose, fasting insulin, or insulin resistance. The magnitude of reduction in blood pressure and lipid indices appears small but may be important clinically. It has been shown that 5 mm reduction in blood pressure reduces the risk of coronary artery disease by 15% and risk of stroke by 42%.  Similarly, 40 mg reduction in LDL cholesterol brings down the risk of stroke and coronary artery disease by 20%.  The change in all these parameters with CPAP therapy is small but in the direction of improvement of metabolic syndrome which makes it more meaningful clinically.
The decrease in BMI and abdominal fat has been attributed to a decrease in daytime somnolence and a consequent increase in physical activity after CPAP use at night. The authors further speculate that a favorable effect on leptin levels with CPAP therapy may be responsible for the effect. Adherence was higher with CPAP than with sham CPAP. Better adherence was associated with greater improvement in metabolic parameters, as confirmed by a subgroup analysis of patients who used CPAP for at least 5 h per night compared to the overall population. Limitations of the study included the fairly short washout period of 1 month, which could not exclude carryover effect of treatment, the lack of ambulatory blood pressure measurement, and the absence of follow-up polysomnographic data.
Previous studies on effects of CPAP therapy on metabolic syndrome have yielded mixed results; most of them showing favorable effects on blood pressure, but data on insulin resistance and lipids have been inconsistent and even conflicting. ,, The strengths of the current study includes large number of patients and a longer follow-up period, as well as being a placebo-controlled, double-blind, randomized, crossover study. The patients included in the study had more severe metabolic abnormalities at baseline, which may have been responsible for the better response to CPAP therapy. Longer term studies are required to study if the benefits are sustained, the effect of adherence to the therapy, and to see any significant effect on carotid intima-media thickness. The present study outcome supports the use of CPAP therapy as a modality of management of metabolic syndrome in patients with OSA in addition to lifestyle modification, weight reduction, and dietary modification. Early identification of metabolic syndrome in patients with OSA and prompt institution of CPAP therapy will help in decreasing the drug requirement for the individual components of metabolic syndrome and considerably decrease the risk factors for cardiovascular disease.
| References|| |
|1.||Reddy EV, Kadhiravan T, Mishra HK, Sreenivas V, Handa KK, Sinha S, et al. Prevalence and risk factors of obstructive sleep apnea among middle-aged urban Indians: A community-based study. Sleep Med 2009;10:913-8. |
|2.||Lam JC, Sharma SK, Lam B. Obstructive sleep apnoea: Definitions, epidemiology and natural history. Indian J Med Res 2010;131:165-70. |
|3.||Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342:1378-84. |
|4.||Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004;25:735-41. |
|5.||Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002;165:670-6. |
|6.||Sharma SK, Reddy EV, Sharma A, Kadhiravan T, Mishra HK, Sreenivas V, et al. Prevalence and risk factors of syndrome Z in urban Indians. Sleep Med 2010;11:562-8. |
|7.||Agrawal S, Sharma SK, Sreenivas V, Lakshmy R. Prevalence of metabolic syndrome in a north Indian hospital-based population with obstructive sleep apnoea. Indian J Med Res 2011;134:639-44. |
|8.||Sharma SK, Kumpawat S, Goel A, Banga A, Ramakrishnan L, Chaturvedi P. Obesity, and not obstructive sleep apnea, is responsible for metabolic abnormalities in a cohort with sleep-disordered breathing. Sleep Med 2007;8:12-7. |
|9.||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;29:720-7. |
|10.||Durán-Cantolla J, Aizpuru F, Montserrat JM, Ballester E, Terán-Santos J, Aguirregomoscorta JI, et al. Spanish sleep and breathing group. Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: Randomised controlled trial. BMJ 2010;341:c5991. |
|11.||Natarajan R. Recent trends in pulmonary arterial hypertension. Lung India 2011;28:39-48. |
|12.||Dorkova Z, Petrasova D, Molcanyiova A, Popovnakova M, Tkacova R. Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome. Chest 2008;134:686-92. |
|13.||Börgel J, Sanner BM, Bittlinsky A, Keskin F, Bartels NK, Buechner N, et al. Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels. Eur Respir J 2006;27:121-7. |
|14.||Mota PC, Drummond M, Winck JC, Santos AC, Almeida J, Marques JA. APAP impact on metabolic syndrome in obstructive sleep apnea patients. Sleep Breath 2011;15:665-72. |
|15.||Sharma SK, Agrawal S, Damodaran D, Sreenivas V, Kadhiravan T, Lakshmy R, et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med 2011;365:2277-86. |
|16.||Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, et al. Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: Overview of randomised drug trials in their epidemiologic context. Lancet 1990;335:1534-5. |
|17.||Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78. |
|18.||Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR. Circulating cardiovascular risk factors in obstructive sleep apnoea: Data from randomised controlled trials. Thorax 2004;59:777-82. |