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      Evaluation of Inflammatory Markers in a Large Sample of Obstructive Sleep Apnea Patients without Comorbidities

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          Abstract

          Systemic inflammation is important in obstructive sleep apnea (OSA) pathophysiology and its comorbidity. We aimed to assess the levels of inflammatory biomarkers in a large sample of OSA patients and to investigate any correlation between these biomarkers with clinical and polysomnographic (PSG) parameters. This was a cross-sectional study in which 2983 patients who had undergone a polysomnography for OSA diagnosis were recruited. Patients with known comorbidities were excluded. Included patients ( n = 1053) were grouped according to apnea-hypopnea index (AHI) as mild, moderate, and severe. Patients with AHI < 5 served as controls. Demographics, PSG data, and levels of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR), and uric acid (UA) were measured and compared between groups. A significant difference was found between groups in hs-CRP, fibrinogen, and UA. All biomarkers were independently associated with OSA severity and gender ( p < 0.05). Females had increased levels of hs-CRP, fibrinogen, and ESR ( p < 0.001) compared to men. In contrast, UA levels were higher in men ( p < 0.001). Our results suggest that inflammatory markers significantly increase in patients with OSA without known comorbidities and correlate with OSA severity. These findings may have important implications regarding OSA diagnosis, monitoring, treatment, and prognosis. This trial is registered with ClinicalTrials.gov number NCT03070769.

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          C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992.

          Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications. Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events. We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein (CRP) with the incidence of first major coronary heart disease (CHD) event in 936 men 45 to 64 years of age. The subjects, who were sampled at random from the general population, participated in the first MONICA Augsburg survey (1984 to 1985) and were followed for 8 years. There was a positive and statistically significant unadjusted relationship, which was linear on the log-hazards scale, between CRP values and the incidence of CHD events (n=53). The hazard rate ratio (HRR) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 (95% CI, 1.29 to 2. 17). After adjustment for age, the HRR was 1.60 (95% CI, 1.23 to 2. 08). Adjusting further for smoking behavior, the only variable selected from a variety of potential confounders by a forward stepping process with a 5% change in the relative risk of CRP as the selection criterion, yielded an HRR of 1.50 (95% CI, 1.14 to 1.97). These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications.
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            Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health).

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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
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi
                0962-9351
                1466-1861
                2017
                31 July 2017
                : 2017
                : 4573756
                Affiliations
                Sleep Disorders Center, Department of Thoracic Medicine, University of Crete, Heraklion, Greece
                Author notes
                *Izolde Bouloukaki: izolthi@ 123456gmail.com

                Academic Editor: Ariadne Malamitsi-Puchner

                Author information
                http://orcid.org/0000-0001-5903-3550
                http://orcid.org/0000-0003-1551-0743
                http://orcid.org/0000-0002-5224-7692
                Article
                10.1155/2017/4573756
                5555019
                28831208
                a1e1f2d3-307e-4f1a-9c89-2a31034bd789
                Copyright © 2017 Izolde Bouloukaki et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 March 2017
                : 19 June 2017
                : 3 July 2017
                Categories
                Clinical Study

                Immunology
                Immunology

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