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      Copeptin: a new predictor for severe obstructive sleep apnea

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          Abstract

          Introduction

          Copeptin which is the C-terminal fragment of antidiuretic hormone (ADH), is a biomarker that has been reported to be increased in various cardiovascular disorders, cerebrovascular diseases and associated with prognosis. Patients with obstructive sleep apnea syndrome (OSAS) have a tendency to develop coronary and cerebral atherosclerotic diseases.

          Objectives

          The aim of the present study was to study copeptin levels in patients with obstructive sleep apnea and in a control group in order to determine whether copeptin could be used as a biomarker predicting the severity of OSAS and possible complications in this group.

          Methods

          A total of 116 patients with OSAS, diagnosed by polysomnography, and 27 controls were included in the study. Blood samples were collected after overnight fasting, and copeptin levels were measured with enzyme-linked immunosorbent assay.

          Results

          Copeptin levels were significantly higher in the OSAS group compared to control group (2,156±502; 1,845±500 pg/mL, respectively, P=0.004). Mean copeptin level of the patients having apnea-hypopnea index (AHI) ≥30 was significantly higher than that of the patients having AHI <30 (2,392±415; 2,017±500 pg/mL, respectively, P<0.001). A multivariate regression analysis showed that copeptin level, (hazard ratio: 1.58; 95% confidence interval: 1.09–2.30) was a predictor of severe OSAS ( P=0.016). Copeptin levels showed significant positive correlation with AHI ( r=0.32; P<0.001), desaturation index ( r=0.23; P=0.012), arousal index ( r=0.24; P=0.010) and CRP ( r=0.26; P=0.011) respectively.

          Conclusion

          Copeptin levels are high in OSAS patients and copeptin is a potential marker for identifying patients with a high risk of early cardiovascular complications of OSAS. Copeptin has modest sensitivity (84%) for discriminating severe OSAS patients who are candidates for severe cardiovascular complications.

          Most cited references29

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          Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study.

          The effect of obstructive sleep apnoea-hypopnoea as a cardiovascular risk factor and the potential protective effect of its treatment with continuous positive airway pressure (CPAP) is unclear. We did an observational study to compare incidence of fatal and non-fatal cardiovascular events in simple snorers, patients with untreated obstructive sleep apnoea-hypopnoea, patients treated with CPAP, and healthy men recruited from the general population. We recruited men with obstructive sleep apnoea-hypopnoea or simple snorers from a sleep clinic, and a population-based sample of healthy men, matched for age and body-mass index with the patients with untreated severe obstructive sleep apnoea-hypopnoea. The presence and severity of the disorder was determined with full polysomnography, and the apnoea-hypopnoea index (AHI) was calculated as the average number of apnoeas and hypopnoeas per hour of sleep. Participants were followed-up at least once per year for a mean of 10.1 years (SD 1.6) and CPAP compliance was checked with the built-in meter. Endpoints were fatal cardiovascular events (death from myocardial infarction or stroke) and non-fatal cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, coronary artery bypass surgery, and percutaneous transluminal coronary angiography). 264 healthy men, 377 simple snorers, 403 with untreated mild-moderate obstructive sleep apnoea-hypopnoea, 235 with untreated severe disease, and 372 with the disease and treated with CPAP were included in the analysis. Patients with untreated severe disease had a higher incidence of fatal cardiovascular events (1.06 per 100 person-years) and non-fatal cardiovascular events (2.13 per 100 person-years) than did untreated patients with mild-moderate disease (0.55, p=0.02 and 0.89, p<0.0001), simple snorers (0.34, p=0.0006 and 0.58, p<0.0001), patients treated with CPAP (0.35, p=0.0008 and 0.64, p<0.0001), and healthy participants (0.3, p=0.0012 and 0.45, p<0.0001). Multivariate analysis, adjusted for potential confounders, showed that untreated severe obstructive sleep apnoea-hypopnoea significantly increased the risk of fatal (odds ratio 2.87, 95%CI 1.17-7.51) and non-fatal (3.17, 1.12-7.51) cardiovascular events compared with healthy participants. In men, severe obstructive sleep apnoea-hypopnoea significantly increases the risk of fatal and non-fatal cardiovascular events. CPAP treatment reduces this risk.
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            Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force.

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              Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure.

              C-reactive protein (CRP) and interleukin (IL)-6 are important risk factors for atherosclerosis and coronary heart disease. In the present study, we examined serum levels of CRP and IL-6, IL-6 production by monocytes, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). After polysomnography, venous blood was collected at 5 AM from 30 patients with OSAS and 14 obese control subjects. Serum levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes were investigated. In addition, the effects of 1 month of nCPAP were studied in patients with moderate to severe OSAS. Levels of CRP and IL-6 were significantly higher in patients with OSAS than in obese control subjects (CRP P<0.001, IL-6 P<0.05). IL-6 production by monocytes was also higher in patients with OSAS than in obese control subjects (P<0.01). In patients with OSAS, the primary factors influencing levels of CRP were severity of OSAS and body mass index and those influencing levels of IL-6 were body mass index and nocturnal hypoxia. nCPAP significantly decreased levels of both CRP (P<0.0001) and IL-6 (P<0.001) and spontaneous IL-6 production by monocytes (P<0.01). Levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes are elevated in patients with OSAS but are decreased by nCPAP. Therefore, OSAS is associated with increased risks for cardiovascular morbidity and mortality, and nCPAP may be useful for decreasing these risks.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2015
                10 April 2015
                : 11
                : 589-594
                Affiliations
                [1 ]Department of Chest Diseases, Recep Tayyip Erdogğan University, Rize, Turkey
                [2 ]Department of Biochemistry, Recep Tayyip Erdogğan University, Rize, Turkey
                Author notes
                Correspondence: Servet Kayhan, Department of Chest Diseases, Recep Tayyip Erdoğan University, 53200 Rize, Turkey, Tel +90 46 4213 0491, Fax +90 46 4217 0364, Email kayhanservet@ 123456gmail.com
                Article
                tcrm-11-589
                10.2147/TCRM.S80779
                4401209
                b258353c-8ac9-4528-a5dd-8a9da0062b87
                © 2015 Çınarka et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Medicine
                copeptin,obstructive sleep apnea,predictor,inflammation
                Medicine
                copeptin, obstructive sleep apnea, predictor, inflammation

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