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Communications to the Editor |

Obstructive Sleep Apnea Causes Systemic Inflammation and Metabolic Syndrome FREE TO VIEW

Shinji Teramoto, MD, FCCP; Hiroshi Yamamoto, MD; Yasuhiro Yamaguchi, MD; Ryoichi Namba, MD; Yasuyoshi Ouchi, MD
Author and Funding Information

The University of Tokyo Hospital, Tokyo, Japan

Correspondence to: Shinji Teramoto, MD, FCCP, Department of Geriatric Medicine, The University of Tokyo Hospital, 7–3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan; e-mail: shinjit-tky@umin.ac.jp



Chest. 2005;127(3):1074-1075. doi:10.1378/chest.127.3.1074
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To the Editor:

In a recent issue of CHEST (July 2004),1 Hatipoglu and Rubinstein pointed out that the possibilities of pathophysiologic link between obstructive sleep apnea syndrome (OSAS) and airway and/or systemic inflammation. They suggested that increased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-sensitivity C-reactive protein (hsCRP) are involved in the pathogenesis of systemic inflammation in OSAS. However, the important and growing issue of metabolic syndrome in patients with OSAS is not argued.

OSAS is recently recognized as a risk factor for cardiovascular disorders and metabolic syndrome.26 OSAS is related to obesity, insulin resistance, and diabetes mellitus. In addition, leptin and insulin levels were elevated in patients with OSAS independently of obesity, and visceral fat was the primary parameter linked with sleep apnea. The association of OSAS with insulin resistance and diabetes type 2 has been confirmed.56 Adiponectin is a hormone secreted by adipocytes that acts as an antidiabetic and antiatherogenic adipocytokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance, and type 2 diabetes. We have found that plasma level of adiponectin is decreased in OSAS patients compared with that in obese control subjects without OSAS.7 The level of adiponectin is associated with the severity of OSAS as indicated by apnea-hypopnea index (AHI), rather than obesity indexed as body mass index. The lower adiponectin level is also associated with increased levels of hsCRP and IL-6.7

At the inflammatory point of view, the levels of TNF-α, IL-6, hsCRP, adhesion molecules, and monocyte chemoattractant protein-1 were markedly and significantly elevated in patients with sleep apnea than those in normal control subjects.89 IL-6 and hsCRP levels were independently associated with OSAS severity as indicated by the AHI. In addition, hsCRP level is associated with visceral adipose tissue and is significantly associated with the components of insulin resistance syndrome.5 These data support the belief that inflammatory processes and metabolic syndrome are activated in atherosclerotic lesions in patients with OSAS. C-reactive protein and other inflammatory cytokines accelerate the progression of atherosclerosis in patients with OSAS. In addition, increase in circulating levels of adenosine and urinary uric acid in patients with obstructive sleep apnea are implicated with increased production of reactive oxygen species. Activation of redox-sensitive gene expression is suggested by the increase in some protein products of these genes, including vascular endothelial growth factor, erythropoietin, endothelin-1, inflammatory cytokines, and adhesion molecules.1011 These results implicate the participation of redox-sensitive transcription factors as hypoxia-inducible factor-1, activator protein-1 and nuclear factor-κB.

Importantly, the elevated levels of atherogenic inflammatory mediators were improved by the OSAS-specific treatment such as nasal continuous positive airway pressure.811 Thus, OSAS plays a crucial role in metabolic syndrome and systemic inflammatory disorders.

This study was supported by the supported by a research grants from Japan Arteriosclerosis Prevention Fund and Danon Institute of Japan.

Hatipoglu, U, Rubinstein, I (2004) Inflammation and obstructive sleep apnea syndrome: how many ways do I look at thee?Chest126,1-2. [CrossRef] [PubMed]
 
Teramoto, S, Ohga, E, Ouchi, Y Obstructive sleep apnoea.Lancet1999;354,1213-1214. [PubMed]
 
Teramoto, S, Kume, H, Matsuse, T, et al The risk of future cardiovascular diseases in the patients with OSAS is dependently or independently associated with obstructive sleep apnoea.Eur Respir J2001;17,573-574. [CrossRef] [PubMed]
 
Teramoto, S, Kume, H, Matsuse, T Ambulatory blood pressure after sleep apnoea treatment.Lancet2002;360,341-342
 
Coughlin, SR, Mawdsley, L, Mugarza, JA, et al Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome.Eur Heart J2004;25,735-741. [CrossRef] [PubMed]
 
Harsch, IA, Schahin, SP, Radespiel-Troger, M, et al Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome.Am J Respir Crit Care Med2004;169,156-162. [PubMed]
 
Teramoto, S, Yamamoto, H, Yamaguchi, Y, et al A significant association of plasma adiponectin level with apnea-hypopnea index rather than BMI in patients with obstructive sleep apnea syndrome [abstract]. Am J Respir Crit Care Med. 2004;;169 ,.:A430
 
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 apnea syndrome [letter]. Circulation. 2003;;107 ,.:E40. [CrossRef] [PubMed]
 
Alexandros, N, Vgontzas,, Dimitris, A, et al Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia.J Clin Endocrinol Metab2000;85,1151-1158. [CrossRef] [PubMed]
 
Teramoto, S, Kume, H, Yamamoto, H, et al Effects of oxygen administration on the circulating vascular endothelial growth factor (VEGF) levels in patients with obstructive sleep apnea syndrome.Intern Med2003;42,681-685. [CrossRef] [PubMed]
 
Ohga, E, Tomita, T, Wada, H, et al Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1.J Appl Physiol2003;94,179-184. [PubMed]
 

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References

Hatipoglu, U, Rubinstein, I (2004) Inflammation and obstructive sleep apnea syndrome: how many ways do I look at thee?Chest126,1-2. [CrossRef] [PubMed]
 
Teramoto, S, Ohga, E, Ouchi, Y Obstructive sleep apnoea.Lancet1999;354,1213-1214. [PubMed]
 
Teramoto, S, Kume, H, Matsuse, T, et al The risk of future cardiovascular diseases in the patients with OSAS is dependently or independently associated with obstructive sleep apnoea.Eur Respir J2001;17,573-574. [CrossRef] [PubMed]
 
Teramoto, S, Kume, H, Matsuse, T Ambulatory blood pressure after sleep apnoea treatment.Lancet2002;360,341-342
 
Coughlin, SR, Mawdsley, L, Mugarza, JA, et al Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome.Eur Heart J2004;25,735-741. [CrossRef] [PubMed]
 
Harsch, IA, Schahin, SP, Radespiel-Troger, M, et al Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome.Am J Respir Crit Care Med2004;169,156-162. [PubMed]
 
Teramoto, S, Yamamoto, H, Yamaguchi, Y, et al A significant association of plasma adiponectin level with apnea-hypopnea index rather than BMI in patients with obstructive sleep apnea syndrome [abstract]. Am J Respir Crit Care Med. 2004;;169 ,.:A430
 
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 apnea syndrome [letter]. Circulation. 2003;;107 ,.:E40. [CrossRef] [PubMed]
 
Alexandros, N, Vgontzas,, Dimitris, A, et al Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia.J Clin Endocrinol Metab2000;85,1151-1158. [CrossRef] [PubMed]
 
Teramoto, S, Kume, H, Yamamoto, H, et al Effects of oxygen administration on the circulating vascular endothelial growth factor (VEGF) levels in patients with obstructive sleep apnea syndrome.Intern Med2003;42,681-685. [CrossRef] [PubMed]
 
Ohga, E, Tomita, T, Wada, H, et al Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1.J Appl Physiol2003;94,179-184. [PubMed]
 
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