Search

Purpose: Soluble vascular adhesion protein-1 (sVAP-1) and adropin are 2 biomarkers of endothelial dysfunction. The main purpose of this study was to evaluate the levels of sVAP-1 in patients with moderate and severe obstructive sleep apnea (OSA) compared to healthy controls, and to further determine the relationship between sVAP-1 and adropin levels, as well as inflammatory biomarkers and sleep parameters., Methods: In this study, we included 50 male patients with OSA (25 moderate and 25 severe) and 20 age- and sex-matched control subjects. Patients with OSA underwent polysomnography. All subjects underwent fasting peripheral blood sampling for laboratory analysis., Results: Serum sVAP-1 and inflammatory biomarkers (IL-6, TNF-α, and hsCRP) levels were significantly higher in patients with severe OSA compared to those with moderate OSA and control groups, while plasma levels of adropin showed the opposite trend. Furthermore, sVAP-1 levels had a significant positive correlation with AHI, ODI, TNF-α, IL-6, and hsCRP levels and a significant negative correlation with adropin levels. The receiver operating characteristic analysis showed an Area Under Curve (AUC) of .876 ( P < .001) for sVAP-1 levels predicting OSA. Serum sVAP-1 threshold of > 445.5 ng/mL had an 88% sensitivity and 80% specificity for detecting OSA status. Multivariate regression analysis demonstrated that sVAP-1 remained a significant positive predictor of OSA severity., Conclusions: Increased sVAP-1 levels in OSA patients are significantly correlated with indices of OSA severity, adropin levels, and inflammatory biomarkers, suggesting that sVAP-1 plays a vital role in the pathophysiology of OSA and may become a potential screening tool in the evaluation of OSA severity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients., Methods: In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA., Results: A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20-3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84-1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar., Conclusion: OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population., Trial Registration: Clinicaltrials.gov; No: NCT03362385., (© 2024. The Author(s).)

Obstructive sleep apnea is associated with cognitive impairment and increased risk for neurodegenerative diseases. Obstructive sleep apnea treatment with positive airway pressure therapy helps to improve cognitive symptoms and reduces long-term dementia risk. To test whether these treatment effects are due to a reduction in neuronal damage, we examined longitudinal changes in the neurodegenerative serum neurofilament light chain and cognitive performance of patients with obstructive sleep apnea. In this study, 17 patients with obstructive sleep apnea completed baseline and follow-up (9 month after starting PAP treatment) investigation of sleep, daytime symptoms, cognitive testing and serum neurofilament light chain measurements. Depending on treatment adherence and efficacy, participants were assigned either to the effective treatment (n = 10) or non-effective treatment group (n = 7). As results at baseline lower mean oxygen saturation during sleep was associated with higher serum neurofilament light chain. Patients in the non-effective treatment group showed a significant increase of age-adjusted percentile of serum neurofilament light chain levels at follow-up, whereas serum neurofilament light chain values remained constant in the effective treatment group. At a functional level, effective treatment leads to an improvement in processing speed, which was not the case in the non-effective treatment group. Longitudinal changes of age-adjusted serum neurofilament light chain levels were associated with changes in cognitive performance. To conclude, this longitudinal observational study showed that effective obstructive sleep apnea treatment positively affects the amount of neuronal damage as well as working memory performance. As cognitive symptoms might not only be attributed to obstructive sleep apnea-related sleep deficiency, but also neurodegeneration, our results underline the importance of treatment adherence and efficacy for the prevention of neuronal damage and cognitive consequences., (© 2024 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Purpose: Obstructive sleep apnoea hypoventilation syndrome (OSAHS) is a common sleep disorder that affects multiple body systems, which in turn is closely associated with cognitive dysfunction, diabetes mellitus, oncological cardiovascular diseases and metabolic disorders. In recent years, non-coding RNA (ncRNA) has emerged as a new opportunity for biomarker discovery. We therefore discuss the research progress and potential role of ncRNAs in obstructive sleep apnea hypoventilation syndrome., Methods: This review systematically searched relevant academic literature from PubMed, Web of Science and other databases. During the retrieval process, a combination of keywords such as "OSAHS", "ncRNA", "lncRNA", "miRAN", "circRNA" was used for search., Results: Circulating ncRNA has good area under the ROC curve, sensitivity and specificity in the diagnosis of OSAHS, and has the potential to become a diagnostic marker for OSAHS, while several circulating ncRNAs or circulating ncRNAs in combination with other tests such as the Obstructive Sleep Apnoea Screening Scale have a higher value of application as a test for OSAHS. Further analyses revealed that many circulating ncRNAs were significantly differentially expressed in the serum of OSAHS patients with different very severities, a potential marker for predicting the severity of OSAHS, and that the ncRNA content of patients' serum also had a significant effect during CPAP therapy, suggesting that it may have potential for therapeutic monitoring. Meanwhile, serum ncRNAs from patients have been shown to be effective in the diagnosis of OSAHS complications such as hypertension, Alzheimer's disease, acute myocardial infarction and atherosclerosis. The expression of up- or down-regulated ncRNAs can regulate different signalling pathways, which in turn affects various OSAHS complications such as pulmonary hypertension, diabetes mellitus, and cognitive dysfunction, and is expected to become a new direction for the treatment of these complications., Conclusions: The changes in ncRNA expression in OSAHS patients are expected to be a novel biomarker for the diagnosis and treatment of OSAHS, and can also be used as a potential biomarker for the combination of diabetes mellitus, cardiovascular disease, respiratory disease, and cognitive dysfunction in OSAHS. It is believed that the continuous progress of ncRNA-related research is expected to promote the early detection, diagnosis and treatment of OSAHS and its complications., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The community population based studies on the relationship between obstructive sleep apnea and liver injury are limited. The study aimed to clarify the association between sleep apnea (SA) and liver injury by using the data in The National Health and Nutrition Examination Survey. SA was assessed by the sleep questionnaire and liver injury was evaluated by liver function test, hepatic steatosis index, and fibrosis-4. Weighted multivariable linear regression was performed to examine the association between SA and liver injury. Subgroup analyses and sensitivity analysis were also conducted. A total of 19,362 eligible participants were included in the study. After adjusting for confounders, the presence of SA was significantly associated with increased levels of lnALT, lnAST/alanine aminotransferase, lnGGT, and lnHSI (all P values < .05), but not with lnFIB-4 (P > .05). There is a dose-response relationship between the severity of SA and increased levels of lnALT, lnGGT, and decreased levels of lnAST/alanine aminotransferase (test for trend, all P values < .05). Subgroup analyses revealed that the positive association between SA and liver function, liver steatosis showed a tendency to exist in nonobese, younger, non-Hispanic Black, and male populations. Sensitive analysis showed the relationship between SA and liver injury was stable. Self-reported SA was independently associated with elevated liver enzymes and liver steatosis among US population. The association was more pronounced among nonobese, younger, non-Hispanic Black, and male populations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Objectives: To determine whether obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort., Methods: Consenting adult patients at the University of British Columbia Hospital between 2003 and 2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram. Blood samples were collected the morning after polysomnography and processed for biomarkers of inflammation and angiogenesis. The clinical, polysomnography, and biomarker data were linked to the British Columbia Cancer Registry to ascertain incident cancer diagnoses. Cox proportional hazard regression was used to assess the association between OSA severity and biomarker concentrations with cancer risk., Results: A total of 1,990 patients were included in the analysis with a mean follow-up time of 12.8 years; 181 of them (9.1%) developed cancer after polysomnography. OSA severity was significantly associated with cancer risk after controlling for relevant covariates (hazard ratio = 1.08 per 10 events/h apnea-hypopnea index increase, confidence interval = 1.02-1.15, P = .015). In an exploratory analysis, 2 biomarkers were significantly associated with an increased cancer risk after controlling for relevant covariates (hazard ratio per interquartile range pg/mL increase of endostatin = 1.45, confidence interval = 1.12-1.87, P = .01 and hazard ratio for interquartile range pg/mL increase of vascular cell adhesion molecule-1 = 1.48, confidence interval = 1.04-2.11, P = .03, respectively)., Conclusions: OSA severity was an independent risk factor for cancer. Furthermore, 2 circulating markers were significantly associated with cancer risk. If these preliminary findings can be reproduced in other cohorts, biomarkers could potentially be used to prognosticate patients with OSA with respect to cancer risk., Citation: Hirsch Allen AJ, Kendzerska T, Bhatti P, et al. Obstructive sleep apnea severity, circulating biomarkers, and cancer risk. J Clin Sleep Med . 2024;20(9):1415-1422., (© 2024 American Academy of Sleep Medicine.)

Objective: To examine the SCUBE1 level, a biomarker in vascular biology that could determine the prognosis of cardiovascular events during OSA treatment., Methods: In total, 129 patients were included in the study. Thirty were diagnosed with simple snoring and 99 with OSA., Results: In males, significant correlation was determined between SCUBE1 non-REM AHI, hypopnea index, total apnea index, mean SO 2 , minimum SO 2 , and < 90% saturation duration., Conclusion: Serum SCUBE1 levels increased more in male patients with severe OSA compared to other OSA levels, and high serum SCUBE1 levels were found to be associated with lower oxygen levels in OSA patients. The SCUBE1 biomarker can correlate with severe OSA in males. There was a statistically significant difference between OSA groups in terms of SCUBE1 score for male patients ( p = 0.002) but not for females ( p = 0.498). It is important that future SCUBE1 studies evaluate males vs. females.

Background: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation., Methods: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients., Results: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 ( r  = -0.19, p  < .05) and LPS ( r  = -0.20, p  < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 ( r  = -0.46, p  < .01), LPS ( r  = -0.35, p  < .01) and CPR ( r  = -0.30, p  < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients., Conclusions: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients.

Background: Increasing evidence suggests an association between childhood obstructive sleep apnea (OSA) and metabolic syndrome, with more research available on the potential impacts of positive airway pressure (PAP) on metabolic markers in children. The purpose of this systematic review is to provide a systematic synthesis of the evidence on the effect of PAP use on metabolic markers in children with OSA., Methods: A search strategy with terms for "OSA" and metabolic markers in pediatrics was run to systematically assess 5 databases until August 26, 2022. Two reviewers independently screened eligible articles, extracted data, and conducted quality appraisal. Meta-analysis was done using random-effects models. Body mass index (BMI), glycemic, lipid, cardiovascular, and other metabolic and inflammatory markers were reported., Results: Sixteen studies ( N = 1,213) were included, 15 observational studies and 1 randomized controlled trial (RCT); most reported outcomes in children with obesity. Meta-analysis of 4 studies found no changes in BMI at median average follow-up of 12 months after PAP initiation. A reduction in heart rate and blood pressure parameters was demonstrated in several studies in children with OSA with and without obesity at a median average follow-up of 4.9 months after PAP initiation. Research in echocardiographic outcomes is limited, including one RCT in children with Down syndrome and OSA showing no changes in heart rate variability parameters. Evidence of improvements in glycemic and/or lipid control, liver enzymes, and inflammatory markers with PAP therapy is even more limited and of limited clinical importance. Risk of bias was moderate to critical and outcome evidence very low., Conclusions: Although evidence on effects of PAP on metabolic markers in children with OSA is encouraging, available literature is limited. Longitudinal studies are still required to further assess the long-term influence of PAP on metabolic and inflammatory markers, particularly in children with obesity., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Objective: To assess whether adenotonsillectomy improves levels of inflammatory and cardiometabolic markers in children with polysomnographically diagnosed obstructive sleep apnea (OSA)., Data Sources: Two authors independently searched PubMed, Embase, and Cochrane databases up to August 16, 2022, for studies relating to pre- and post-operative levels of serum markers in pediatric patients undergoing adenotonsillectomy., Review Methods: Data were extracted from included articles into a structured proforma. Meta-analyses of the standardized mean difference (SMD) were conducted in random-effects models. We calculated the probability of benefit (POB) and number needed to treat (NNT) for outcomes that demonstrated a statistically significant effect after adenotonsillectomy. The primary outcomes were changes in serum markers including C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), Insulin-like growth factor 1 (IGF-1), interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Brain natriuretic peptide (BNP), insulin, glucose, total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL)., Results: We screened 1616 studies and included 26 studies with 1331 participants. Meta-analysis was performed on 20 of the included studies. Adenotonsillectomy was associated with a significant decrease in insulin levels (SMD = -0.322, 95% Confidence Interval (CI) = -0.583 to -0.061), CRP (SMD = -0.946, 95% CI = -1.578 to -0.314), and BNP (SMD = -1.416, 95% CI = -2.355 to -0.477) and significant increase in levels of IGF-1 (SMD = 0.691, 95% CI = 0.207 to 1.176). There were no significant changes in levels of triglyceride, total cholesterol, TNF-α, LDL, HDL, glucose, IL-10, and IL-6., Conclusion: In children with polysomnographically diagnosed OSA, adenotonsillectomy was associated with improvements in serum biomarkers, comprising lower CRP, insulin, and BNP, and higher IGF-1. Laryngoscope, 134:3030-3037, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a common condition in the general population and causes significant OSA-associated morbidities including cardiovascular and cerebrovascular events such as cerebral small vessel disease (CSVD) and stroke., Methods: In this study, using sensitive ELISA immunoassays, we measured subset of endothelial/vascular and inflammatory biomarkers as well as neurofilament light chain (NfL), a sensitive marker for neuroaxonal injury, using plasma from OSA patients post-stroke (Acute Cerebral Infarction (ACI), N = 26) to determine their usefulness as potential prognostic markers in disease progression., Results: Our results showed significantly increased plasma TNFα and NfL concentrations and decreased concentrations of platelet derived growth factor (PDGF-AA) in post-stroke OSA patients with more severe white matter hyperintensities (WMHs). And after separating the patients based on sex, compared to females, male post-stroke OSA patients with severe WMHs have increased circulating levels of inflammatory chemokine CXCL10 and cytokine Interleukin-10 (IL-10) and significantly decreased levels of Angiopoietin-1 (Ang-1) an important protein responsible for endothelial/vascular integrity functions. Importantly, in a subset of newly diagnosed OSA patients (without prior history of stroke), significantly increased plasma CXCL10 levels and decreased plasma Ang-1 levels were also readily observed when compared to healthy controls, indicating possible altered endothelial integrity and ongoing vascular inflammation in these newly diagnosed OSA patients., Conclusions: In summary, our study has identified a novel set of plasma biomarkers including PDGF-AA, CXCL10 and Ang-1 for their potential prognostic value for disease outcomes pre- and post-stroke in OSA patients and use as surrogate markers to measure efficacy of treatment modalities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Endocan, as an endothelial cell damage marker, plays role in several cardiovascular and non-cardiovascular diseases. This systematic review and meta-analysis evaluates the role of endocan as a potential diagnostic or prognostic biomarker for obstructive sleep apnea (OSA). International databases including PubMed, Embase, Web of Science, and Scopus were searched for relevant studies assessing endocan levels in OSA patients compared with healthy controls or within different severities or comorbidities of OSA. Random-effect meta-analysis was performed in order to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) of serum/plasma endocan in all comparisons. A total of 10 studies were included in our systematic review, among which seven were used in meta-analysis. Meta-analysis showed that endocan levels were significantly higher in patients with OSA compared with healthy controls (SMD 1.29, 95% CI 0.64-1.93, P < .001) and this was not different between serum and plasma subgroups. However, there was no statistical difference between severe and non-severe OSA patients (SMD .64, 95% CI -.22 to 1.50, P = .147). Considerably, higher endocan levels in patients with OSA in comparison with non-OSA individuals might have clinical implications. This association warrants further research due to its potential use as a diagnostic and prognostic biomarker., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA., Methods: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels., Results: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age., Conclusion: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers., Competing Interests: The authors report no conflicts of interest in this work.

Background: Previous studies have revealed that sleep structure and hypoxemia are two important environmental factors for cognitive impairment in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that the pathophysiological mechanisms between these two factors may also be involved in cognitive impairment in patients with OSAHS. Previous studies have suggested that alterations in serum glucose and lipid metabolism, inflammatory responses, and astrocyte markers not only contribute to sleep structural disorders in OSAHS but also affect the occurrence and development of this disease. Therefore, we hypothesized that alterations in the abovementioned indicators may be involved in cognitive impairment in OSAHS. Additionally, obesity is an important risk factor for OSAHS. This study therefore aimed to explore the correlation between serum indicators and cognitive impairment in patients with OSAHS., Methods: Patients with OSAHS who underwent polysomnography in our hospital were recruited in this study. The overall cognitive function of patients were evaluated using the Mini mental State Examination (MMSE). Blood biochemical indicators such as glucose (GLU), triglycerides (TG), and triglyceride glucose (TyG) index were measured. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of serum glucagon-like peptide-1 receptor (GLP-1R), fibroblast growth factor 21 (FGF21), S100 calcium binding protein B (S100B), brain derived neurotrophic factor (BDNF), inflammatory factors such as C-reactive protein (CRP), tumor necrosis factor-α (TNFα), interleukin-4 (IL-4), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Spearman correlation analysis was used to determine if the indicator was related to cognitive function, and backward linear regression analysis was used to identify the main risk factors for cognitive impairment in non-obese and obese patients with OSAHS., Results: Among 34 patients, 19 were non-obese and 15 were obese. Obese patients exhibited higher AHI compared to non-obese individuals, and the difference was statistically significant (p < 0.05). In non-obese patients, Spearman correlation analysis revealed a negative correlation between serum GLU, IL-4, and MMSE scores (p < 0.05); IL-6 was positively correlated with MMSE (p < 0.05). In addition, GLU and IL-6 were independently correlated with MMSE in non-obese patients (p < 0.05). In obese patients, serum TG and TyG were positively correlated with MMSE scores (p < 0.05); age, BMI, and IL-4 were negatively correlated with MMSE scores (p < 0.05). In addition, age and IL-4 were independently correlated with MMSE in obese patients (p < 0.05)., Conclusions: Our data suggested that GLU and IL-6 were independently correlated with cognitive impairment in non-obese patients with OSAHS; age and IL-4 were independently correlated with cognitive impairment in obese patients. Early detection of this difference in heterogeneity may provide theoretical support for future investigations in prevention and treatment of cognitive impairment in patients with OSAHS., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To determine the significance of immunological markers in patients with obstructive sleep apnea (OSA) and comorbid pathology., Material and Methods: Sixty-five patients were examined. Two groups of patients were distinguished: the main group with moderate and severe OSA and the control group without OSA. The subjects underwent anthropometry, polysomnography, assessment of cognitive and emotional disorders. Glial fibrillar acidic protein (GFAP), antibodies against NR1-NR2 subunits of NMDA receptors (AT to GRIN2A) and the acetylcholine receptor (AT to AChR), and brain-derived neurotrophic factor (BDNF) were studied by enzyme immunoassay., Results: In patients with OSA, indicators of markers: GFAP ( p =0.017), BDNF ( p =0.006), antibodies to AChR ( p =0.002), as well as chronic cerebral ischemia ( p =0.000), depression on the HADS ( p =0.004) and the Beck scale ( p =0.000), drowsiness on the Epworth scale ( p =0.001), asthenia on the visual analogue scale ( p =0.000) and the MFI 20 ( p =0.013) were higher than in the control group. A relationship was established in the main group between the identified subjective disorders on the Mini-Mental State Examination scale (MMSE) and BDNF ( r =0.302, p =0.014) and the average score on the MMSE and BDNF ( r =-0.266, p =0.032)., Conclusion: The results demonstrate the relationship of neurospecific proteins with cognitive impairment in patients with OSA. The neuromarker GFAP in patients with sleep apnea has shown itself to be a predictor of decreased neurogenesis, and BDNF as a representative marker of neuroplasticity. Large values of AT to AChR in patients with OSA may indicate possible neuromuscular transmission disorders. Along with drowsiness and asthenia, patients with OSA have changes in the emotional background, mainly due to depression. The severity of depression and the severity of asthenia increase with increasing severity of apnea and are probably associated with low levels of saturation, which in turn leads to dysregulation of the prefrontal cortex, hippocampus and amygdala.

IGFBP4 is the smallest member of the insulin-like growth factor binding protein family (IGFBP). It is a hepatic protein that plays a role in modulating the activity and bioavailability of IGF-I. The expression of IGFBP4 was found to increase under conditions of hypoxia. Obstructive sleep apnea (OSA) is a common disorder, characterized by cyclic episodes of intermittent hypoxia and fragmented sleep. Our aim was to quantify levels of circulating IGFBP1, IGFBP2, IGFBP3, IGFBP4, and IGFBP7 in fasting plasma samples of 69 Kuwaiti participants and explore its correlation with indices of OSA. The quantification was performed using multiplexing assay. The study involved 28 controls and 41 patients with OSA. Levels of circulating IGFBP4 were significantly higher in people with OSA (289.74 ± 23.30 ng/ml) compared to the control group (217.60 ± 21.74 ng/ml, p = 0.028). The increase in IGFBP4 correlated significantly and positively with AHI ( r = .574, p = .01) and AI ( r = .794, p = .001) in people with moderate and severe OSA. There was a significant decline in circulating IGFBP4 after 3 months of surgery (225.89 ± 18.16 ng/ml, p = 0.012). This was accompanied by a prominent improvement in OSA (AHI 8.97 ± 2.37 events/h, p = 0.001). In this study, our data showed a significant increase in circulating IGFBP4 in people with OSA. We also report a significant positive correlation between IGFBP4 and indices of OSA at baseline, which suggests IGFBP4 as a potential diagnostic biomarker for OSA. There was a significant improvement in OSA after 3 months of surgical intervention, which concurred with a significant decline in IGFBP4 levels. Altogether, the detected change suggests a potential link between IGFBP4 and OSA or an OSA-related factor, whereby OSA might play a role in triggering the induction of IGFBP4 expression., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Abdulmohsen Alterki et al.)

Patients with obstructive sleep apnea (OSA) experience partial or complete upper airway collapses during sleep resulting in nocturnal hypoxia-normoxia cycling, and continuous positive airway pressure (CPAP) is the golden treatment for OSA. Nevertheless, the exact mechanisms of action, especially the transcriptome effect of CPAP on OSA patients, remain elusive. The goal of this study was to evaluate the longitudinal alterations in peripheral blood mononuclear cells transcriptome profiles of OSA patients in order to identify the hub gene and immune response. GSE133601 was downloaded from Gene Expression Omnibus (GEO). We identified black module via weighted gene co-expression network analysis (WGCNA), the genes in which were correlated significantly with the clinical trait of CPAP treatment. Finally, eleven hub genes (TRAV10, SNORA36A, RPL10, OBP2B, IGLV1-40, H2BC8, ESAM, DNASE1L3, CD22, ANK3, ACP3) were traced and used to construct a random forest model to predict therapeutic efficacy of CPAP in OSA with a good performance with AUC of 0.92. We further studied the immune cells infiltration in OSA patients with CIBERSORT, and monocytes were found to be related with the remission of OSA and partially correlated with the hub genes identified. In conclusion, these key genes and immune infiltration may be of great importance in the remission of OSA and related research of these genes may provide a new therapeutic target for OSA in the future., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to investigate the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and obstructive sleep apnea (OSA) in patients with hypertension. A total of 246 hypertensive patients (67 controls, 65 mild, 51 moderate, and 63 severe OSA) were included. The relationship between MHR and OSA was analyzed. MHR correlated positively with apnea-hypopnea index (AHI), while negatively with mean SpO 2 (P < 0.01). MHR was higher in OSA group than the control group (9.2 ± 2.6 vs. 10.8 ± 3.6, P < 0.001). Moreover, MHR in severe OSA group was the highest among all groups (9.2 ± 2.6, 10.2 ± 3.2, 10.4 ± 4.0, and 11.8 ± 3.4 in control, mild, moderate, and severe OSA group, respectively, P < 0.001). Logistic regression analysis demonstrated that MHR was an independent predictor of the presence of OSA (OR = 1.152, P < 0.01) and severe OSA (OR = 1.142, P < 0.01). Area under the curve of MHR was 0.634 (P < 0.05) and 0.660 (P < 0.05) for predicting OSA and severe OSA respectively in the ROC analysis. In conclusion, MHR increased with the severity of OSA. As a practical and cost-effective test, MHR was expected to be an available marker in evaluating OSA risk and severity in hypertensive patients., (© 2021. The Author(s).)

Background: Obstructive sleep apnea syndrome (OSAS) is one of the most common sleep-related breathing disorders. The aim of this study was to improve diagnostics in OSAS using blood circulating biomarkers. We consider the potential of cardiac-specific miRNAs in the diagnosis and risk assessment of cardiovascular complications. Materials & methods: Plasmatic levels of miR-1-3p, miR-133a-3p and miR-499a-5p were measured by reverse transcription-PCR and compared with the clinical status of OSAS patients and controls. Results: The level of miR-499 was higher (p = 0.0343) in OSAS patients (mean expression: 0.00561) compared with the controls (mean expression: 0.00003), using the multivariate logistic regression. Conclusion: The role of miR-499 in gene expression regulation during hypoxia and our findings indicate that miR-499 could be a new diagnostic biomarker for OSAS.

Background: Systemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)-35 and IL-37 have been identified as novel immune-modulating cytokines with anti-inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL-35 and IL-37 in patients with OSA, and to investigate their associations with the severity of OSA., Methods: A total of 97 patients, including 67 cases of OSA and 30 age- and gender-matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL-35, IL-37, and pro-inflammatory cytokine IL-1β levels were examined by ELISA., Results: Compared with those in the control subjects, serum IL-35, IL-37, and IL-1β levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity-dependent increase in serum IL-35 and IL-37 levels was observed in patients with OSA. IL-35 and IL-37 levels were positively correlated with the apnea-hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = -0.461 and -0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = -0.616 and -0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL-35 or IL-37 and IL-1β levels (all p < 0.001)., Conclusion: The serum levels of IL-35 and IL-37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL-35 and IL-37 may have a protective role in OSA by counteracting inflammatory responses., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Aim: Obstructive sleep apnea (OSA) activates the complement system; however, the levels of membrane attack complex (MAC) are unaltered suggesting regulatory mechanisms. Our aim was to investigate complement factor H (CFH) and clusterin, two important complement regulators in OSA. Materials & methods: We analyzed clusterin and CFH levels in plasma of 86 patients with OSA and 33 control subjects. Results: There was no difference in CFH levels between patients (1099.4/784.6-1570.5/μg/ml) and controls (1051.4/652.0-1615.1/μg/ml, p = 0.72). Clusterin levels were higher in patients with OSA (309.7/217.2-763.2/μg/ml vs 276.1/131.0-424.3/μg/ml, p = 0.048) with a trend for a positive correlation with disease severity (p = 0.073). Conclusion: Increase in clusterin levels may be protective in OSA by blocking the MAC formation.

Background: Obstructive sleep apnea (OSA) is a serious threat to individual health. Diagnosis of OSA is mainly polysomnography (PSG). However, PSG monitoring is costly and time-consuming. At present, increasing studies are exploring new diagnostic methods for OSA. This study aimed to explore the diagnostic role of Sestrin2 in OSA. Materials and Methods: Sixty-four subjects were recruited in this study. The concentration of plasma Sestrin2 of all subjects were measured and compared. Spearman's correlation analysis was used to investigate the correlation between plasma Sestrin2 concentration and other factors. Receiver-operating characteristic (ROC) curve was used to investigate the role of Sestrin2 in the diagnosis of OSA, moderate-severe and severe OSA. Results: Subjects were divided into OSA group ( n  = 38) and control ( n  = 26). Levels of Plasma Sestrin2 were significantly higher in OSA patients than in controls. Sestrin2 was positively correlated with oxygen reduction index and negatively correlated with mean oxygen saturation and lowest oxygen saturation. The area under ROC curve (AUC) of Sestrin2 for OSA diagnosis was 0.740 [95% confidence interval (CI), 0.615-0.842], the cutoff value was 1.86 ng/mL, and the sensitivity and specificity were 81.58% and 61.54%, respectively. The AUC of Sestrin2 for the diagnosis of severe OSA was 0.801 (95% CI, 0.682-0.890), and the cutoff value was 5.21 ng/mL exhibiting the sensitivity and specificity of 61.90% and 90.70%, respectively. Conclusion: Setrin2 is a marker for OSA and may be helpful in the diagnosis of OSA.

Background: Obstructive sleep apnea (OSA) was highly prevalent in patients with type 2 diabetes (T2D). Cathepsin S (CTSS), a cysteine protease, is involved in the inflammatory activity in T2D and hypoxia conditions. The aim of the study was to evaluate whether CTSS could be involved in the inflammatory reaction of OSA in patients with T2D., Methods: We included 158 participants in this study matched for age, gender, and body mass index in 4 groups (control, non-OSA&T2D, OSA&non-T2D, and OSA&T2D). After overnight polysomnography, we collected the clinical data including anthropometrical characteristics, blood pressure, and fasting blood samples in the morning. Plasma CTSS concentration was evaluated using the human Magnetic Luminex Assay., Results: Compared with the control group, both the non-OSA&T2D group and the OSA&non-T2D group showed higher CTSS levels. Plasma CTSS expression was significantly increased in subjects with OSA&T2D compared to subjects with non-OSA&T2D. The OSA&T2D group had higher CTSS levels than the OSA&non-T2D group, but there were no statistically significant differences. Plasma CTSS levels showed significant correlation with the apnea-hypopnea index (AHI) ( r = 0.559, P < 0.001) and plasma fasting blood glucose ( r = 0.427, P < 0.001). After adjusting confounding factors, plasma CTSS levels were independently associated with the AHI (Beta: 0.386, 95% confidence intervals (CI): 21.988 to 57.781; P < 0.001). Furthermore, we confirmed the higher pinpoint accuracy of plasma CTSS in the diagnosis of OSA (area under the curve: 0.868)., Conclusions: Plasma CTSS expression was significantly elevated in the OSA&T2D group and was independently associated with the AHI; it could be a biomarker with a positive diagnostic value on diagnosing OSA among patients with T2D., Competing Interests: All authors do not have any conflicts of interest., (Copyright © 2020 Wanwan Wen et al.)

Obstructive sleep apnea syndrome (OSAS) is considered a low-grade chronic inflammatory disease. Interleukin-6 (IL-6) is one of the most significant inflammatory markers and an excellent proxy for the inflammatory/immune system. The present meta-analysis and meta-regression aimed at comparing plasma and serum levels of IL-6 between individuals (children and adults) with OSAS and healthy controls. Four databases, PubMed/Medline, Scopus, Cochrane Library, and Web of Science, were comprehensively searched to retrieve articles published up to December, 2019, with no further restrictions. RevMan 5.3 software was used to calculate the crude mean difference (MD) and 95% confidence interval (CI). The results of funnel plots and meta-regression were analyzed by the CMA 2.0 software. Sixty-three studies (57 with adults; six with children) were included in the present meta-analysis. For adults, 37 studies reported significantly higher serum IL-6 levels and 20 reported significantly higher plasma IL-6 levels for those with OSAS than for healthy controls [pooled MD of 2.89 pg/ml ( P < 0.00001) and pooled MD of 2.89 pg/ml ( P < 0.00001), respectively]. The pooled analysis of serum and plasma IL-6 levels in children with OSAS compared with controls revealed that only the MD of plasma IL-6 levels was significant (MD = 0.84 pg/ml, P = 0.004). Results of the meta-regression showed that greater age was associated with higher serum IL-6 levels. Egger's test revealed a publication bias across the studies for serum and plasma IL-6 levels ( P = 0.00044 and P = 0.01445, respectively). In summary, the meta-analysis and meta-regression confirmed that, compared to healthy controls, individuals with OSAS (children and adults) had higher serum/plasma IL-6 levels., (Copyright © 2020 Imani, Sadeghi, Khazaie, Emami, Sadeghi Bahmani and Brand.)

Rationale : Knowledge of sex-specific changes of cardiovascular biomarkers in response to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) is limited. Objectives : We hypothesized a differential sex-specific cardiovascular biomarker response with CPAP therapy for OSA. Methods : Participants with moderate-severe OSA (apnea-hypopnea index, 15 events/h) were randomized to CPAP versus sham and completed polysomnography and collection of biomarkers of inflammation (myeloperoxidase, fibrinogen, paraoxonase, interleukin [IL]-6, IL-6 soluble receptor, aryl esterase, oxidized low-density lipoprotein, lipoprotein A, plasminogen activator inhibitor 1, and F 2 -isoprostane urine/creatinine ratio) and vascular measures at baseline and 8 weeks of therapy with either CPAP ( n  = 72) or sham treatment ( n  = 70). Post hoc secondary analyses of sex-study arm interaction relative to change in inflammatory biomarkers were evaluated via linear regression with adjustment for baseline biomarker value, age, race, body mass, index, waist circumference, and CPAP adherence. Interactions were further evaluated via sex-stratified analyses. Results : The study sample comprised a total of 149 participants aged 50.8 ± 11.7 years; 55% were male, and 55% were white. Participants had a median apnea-hypopnea index of 26.3 events per hour (interquartile range, 13-37). There were substantial interactions between study arm and sex for myeloperoxidase, paraoxonase, and fibrinogen ( P  = 0.03, P  = 0.03, and P  = 0.08, respectively). No significant interactions were found for the vascular measures. Estimates were similar but with decreased power in sex-stratified analyses, with decreased biomarkers in women and increased biomarkers in men. Conclusions : Differential sex-specific responses to CPAP therapy for OSA were observed for circulating inflammatory biomarkers, which persisted after adjustment for confounders. These findings set the stage for validation studies and, if confirmed, biochemical pathway elucidation to inform sex-specific personalized treatment approaches.Clinical trial registered with www.clinicaltrials.gov (NCT00607893).

Objectives: Sleep apnea syndrome affects approximately 4% of adult males and 2% of adult females. It is associated with significant cardio-, cerebrovascular, metabolic and hormonal comorbidities and ranks among the more expensive medical specialties due to the requirement of high-quality technical diagnostic and therapeutic equipment as well as well-educated and experienced personnel. The aim of this study is to detect the relationship between C-reactive protein (CRP), pentraxin-3 (PTX-3), interleukin 6 (IL6), high-sensitivity troponin I (hsTnI), brain natriuretic protein (BNP) and galectin-3 serum levels and obstru-ctive sleep apnea syndrome., Design: Prospective cohort study., Material and Methods: A group of 146 patients with middle to severe obstructive sleep apnea syndrome (OSAS) were monitored, and the results were compared with the results from a control group of healthy individuals., Results: We assessed serum levels of the following biomarkers: CRP, PTX-3, IL6, hsTnI, BNP, and galectin-3. PTX-3 serum levels were statistically significantly higher (p<0.0001) in patients with OSAS, compared to controls. Statistical results related to the other biomarkers did not suggest any clinical value. ROC analysis showed that PTX-3 might be able to distinguish patients with OSAS from healthy individuals (AUC=7438)., Conclusion: The elevation of PTX-3 serum levels is significantly associated with middle to severe obstructive sleep apnea syndrome. The PTX-3 biomarker appears to be a promising alternative method for sleep apnea syndrome investigations.

Background: Acute coronary syndrome (ACS) is a major cause of death and closely related with obstructive sleep apnea (OSA). Our hypothesis is that several cardiovascular-related biomarkers could have a differential prognostic value for ACS severity in patients with OSA, and could also help (individually or combined) in the detection of OSA in patients after a coronary event., Methods: Up to 361 consecutive individuals admitted due to ACS were included in the study. All of them were evaluated for ACS severity (Killip score, number of diseased vessels, ejection fraction) and further classified as OSA or non-OSA. Medical records were registered and eleven blood biomarkers were measured, including heart-type fatty acid-binding globulin, N-terminal pro-brain natriuretic peptide, matrix metalloproteinase-9 (MMP9), placental growth factor (PlGF) and high-sensitivity C-reactive protein. Odds ratios of every biomarker for ACS severity-related parameters were calculated and adjusted for age, gender, body-mass index (BMI), hypertension, diabetes, smoking and drinking. The use of clinical measures and biomarkers for the diagnosis of OSA in ACS patients was evaluated both alone and combined using ROC curves., Results: Several biomarkers showed a significant association with ACS severity, which remained after adjusting for OSA and other potentially confounding variables. The mathematical combination of age, BMI, PlGF and MMP9 showed an area under the ROC curve (AUC) for OSA identification of 0.741, which was greater than any individual parameter or combination assessed: AUC(BMI):0.687, AUC(age):0.576, AUC(PlGF):0.584, AUC(MMP9):0.555., Conclusions: The usefulness of biomarkers in the assessment of ACS severity was independent of OSA and the other variables evaluated. In patients admitted after a coronary event, the combination of clinical measures and biomarkers showed a significant discriminating power for the detection of OSA., Clinical Trial Registration: NCT01335087 (clinicaltrials.gov)., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose: There are currently no biomarkers that are associated with cognitive impairment (CI) in patients with obstructive sleep apnea syndrome (OSAS). This pilot study performed an exploratory plasma proteomic analysis to discover potential biomarkers and explore proteomic pathways that differentiate OSAS subjects with and without CI., Methods: Participants were selected from a cohort of women within 5 years of menopause not on hormone replacement therapy between the ages of 45-60 years. The Berlin questionnaire was used to select OSAS participants who then completed the MCFSI (Mail-In Cognitive Function Screening Instrument) to measure cognition. Six subjects with the highest MCFSI scores (≥ 5 denoting CI) were compared to six with normal scores. Proteomic analysis was done by Myriad RBM using a targeted ELISA for 254 serum proteins. Pathway analysis of differentially expressed proteins was performed using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) software., Results: Distinct proteomic signatures were seen in OSAS subjects with CI as compared to those without CI. Proteins including insulin, prostasin, angiopoietin-1, plasminogen activator inhibitor 1, and interleukin-1 beta were overexpressed in OSAS subjects with CI. Proteins underexpressed in CI participants included cathepsin B, ceruloplasmin, and adiponectin. Pathway analysis revealed prominence of insulin-regulated vascular disease biomarkers., Conclusions: Proteomic biomarkers in participants with cognitive impairment suggest roles for insulin, and vascular signaling pathways, some of which are similar to findings in Alzheimer's disease. A better understanding of the pathogenic mechanisms of CI in OSAS will help focus clinical trials needed in this patient population.

Study Objectives: Previous research revealed a positive correlation between endothelial cell injury (indicated by albuminuria) and obstructive sleep apnea (OSA). However, little else has been revealed about acute kidney injury (AKI) in patients with OSA., Methods: This prospective study recruited consecutive patients undergoing overnight polysomnography for evaluation of sleep apnea. Patients in whom any major disease or recent infection had been previously diagnosed were excluded. Ultimately, data from 75 patients with apnea-hypopnea indices of 5 or more were analyzed. Baseline values for the urinary albumin-creatinine ratio (UACR), serum levels for three markers of AKI (cystatin C, neutrophil gelatinase-associated lipocalin [NGAL], interleukin-18 [IL-18]), and polysomnography data were recorded and analyzed. Patients then were followed for 6 months of continuous positive airway pressure (CPAP) treatment., Results: At baseline, UACRs were greater in patients with more severe OSA ( P = .005, r = .329). All three serum markers of AKI (cystatin C, NGAL, and IL-18) studied were positively correlated with OSA severity, and two (cystatin C and IL-18) were positively correlated with the frequency of oxygen desaturation during sleep. However, none of the AKI markers had positive correlations with UACR. After 6 months of CPAP treatment, UACR and IL-18 were decreased significantly in patients with good adherence., Conclusions: Albuminuria and levels of three serum markers of AKI (cystatin C, NGAL, IL-18) were positively correlated with OSA severity, and good adherence with CPAP treatment decreased albuminuria and interleukin-18 levels. These results may provide additional tools for assessing early renal injury in patients with OSA., (© 2019 American Academy of Sleep Medicine.)

Oxidative stress underlies both obstructive sleep apnea (OSA) and atherosclerosis. The aim of the study was to assess the markers of oxidative stress in plasma at different stages of OSA in non-smoking obese Caucasian males aged 41-60, with normal oral glucose tolerance test. All patients were subjected to clinical and polysomnographic examinations. The stage of OSA severity was set according to the following criteria of the apnea-hypopnea index (AHI): AHI < 5/h - no disease (OSA-0; n = 26), AHI 5-15/h - mild disease (OSA-1; n = 26), AHI 16-30/h - moderate disease (OSA-2: n = 27), and AHI > 30/h obstructive episodes per hour - severe disease (OSA-3; n = 27). Plasma total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS), reflecting the level of lipid peroxides, were determined spectrophotometrically. We found that TAS decreased and TBARS increased significantly from OSA-0 to OSA-3. We conclude that the oxidative stress markers are conducive to setting the severity of OSA in normoglycemic patients.

Purpose: Obesity, type 2 diabetes mellitus (T2DM), and obstructive sleep apnea (OSA) are associated with chronic low-grade inflammation. Iron metabolism is linked with insulin-resistant states and with OSA in adults. The association of body iron status with T2DM in children remains undefined. We aimed to evaluate plasma interleukin-6 (IL-6), hepcidin, and soluble transferrin receptor (sTfR) levels in obese patients with T2DM or impaired glucose tolerance (IGT) and in those without, and the contribution of OSA to their levels., Methods: In this cross-sectional study, obese children and adolescents with and without T2DM/IGT underwent overnight polysomnography. Fasting plasma concentrations of IL-6, hepcidin, and sTfR were measured and evaluated according to glycemic status (T2DM/IGT and normal glucose tolerance) and the presence of OSA., Results: Ten patients with T2DM (age 15.9 ± 3.6 years), 8 with IGT (age 13.1 ± 2.5 years) and 20 subjects with normal glucose tolerance matched for body mass index standard deviation score (age 12.6 ± 3.3 years) were studied. Sleep measures or IL-6, hepcidin, and sTfR levels were not significantly different between the group with T2DM/IGT vs. the control group. No significant differences were found in hepcidin or sTfR levels between patients with OSA and those without. However, patients with OSA showed higher plasma IL-6 values compared with those without (4.56 ± 2.92 vs. 2.83 ± 1.54 pg/ml, P = 0.025), and the highest values were evident in patients affected by both T2DM/IGT and OSA., Conclusions: Higher IL-6 levels were associated with both glycemic status and OSA. No differences in body iron regulator levels were found in obese patients with T2DM/IGT compared to those without or in those with OSA compared to those without. Further longitudinal studies in larger population samples are warranted.

To review the application of proteomics and metabolomics in the study of OSAHS biomarkers,and to open a new perspective for the study of OSAHS. At present,these studies are still in a very preliminary stage,the results are not always consistent,and far from the clinical application requirements. However,compared with traditional chemical methods,quantitative protein and metabolomics methods still have many advantages and have great clinical potential. Further studies of larger populations for more detailed grouping in the future are necessary to validate these results,and a more structured investigation in cell and animal models is necessary to determine their molecular mechanisms. In addition,the combination of different analytical platforms will be the ideal method for OSAHS biomarker research. In conclusion,the proteomics and metabolomics methods help us to better understand the potential mechanisms of OSAHS and to discover and develop personalized screening,diagnosis,prognostic and therapeutic strategies for future research., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objectives: The aim of the present study was to assess thiol/disulfide (SS) homeostasis as a novel indicator of oxidative stress in patients with obstructive sleep apnea (OSA) and to investigate the effect of continuous positive airway pressure (CPAP) therapy on oxidative parameters., Study Design: Prospective clinical study., Methods: A total of 104 subjects, 44 in an OSA group and 60 in two control groups (control simple snoring group, control OSA group) were included. The levels of parameters were measured using the Erel and Neselioglu method in patients with moderate or severe OSA before and after CPAP therapy., Results: The serum native thiol (SH) and total SH levels as well as the %SH/total SH ratio were significantly lower (P < 0.05) in OSA patients compared to controls, and the SS level and %SS/SH and %SS/total SH ratios were significantly higher (P < 0.05). After CPAP therapy, the native SH level and %SH/total SH ratio were significantly higher (P < 0.05) than before CPAP therapy, and the SS level and %SS/SH and %SS/total SH ratios were significantly lower (P < 0.05). Significant negative correlations were evident between the apnea/hypopnea index (AHI) and the native SH level and %SH/total SH ratio (P < 0.05) before CPAP therapy; and significant positive correlations were seen between the AHI and the %SS/SH and %SS/total SH ratios but not with the SS level., Conclusion: We found that oxidative stress was increased and CPAP therapy had a positive effect in patients with moderate or severe OSA., Level of Evidence: 3b. Laryngoscope, 127:E244-E250, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Study Objectives: Nucleosomes and cell-free double-stranded DNA (dsDNA) have been suggested as promising biomarkers in cell death-related diseases, such as acute coronary syndrome (ACS). Currently, the impact of obstructive sleep apnea (OSA) in patients with ACS is unclear. Our aim was to evaluate the relationship between OSA, dsDNA, and nucleosomes and to assess their potential implication in the development of ACS., Methods: Up to 549 patients were included in the study and divided into four groups (145 ACS; 290 ACS + OSA; 62 OSA; 52 controls). All patients underwent a sleep study, and serum concentrations of dsDNA and nucleosomes were measured., Results: Nucleosome and dsDNA levels were higher in patients with OSA than in controls (nucleosomes: 1.47 ± 0.88 arbitary units [AU] vs. 1.00 ± 0.33 AU; p < .001, dsDNA: 315.6 ± 78.0 ng/mL vs. 282.6 ± 55.4 ng/mL; p = .007). In addition, both biomarker levels were higher in patients with ACS than in non-ACS, independently of the presence of OSA., Conclusions: Both nucleosomes and dsDNA are increased in patients with OSA and might be related with the high cardiovascular risk seen in these patients. The extensive cell lysis during a myocardial infarction seems to be the major contributor to the high biomarker levels, and OSA does not seem to be implicated in such elevation when this acute event occurs., Clinical Trial Registration: NCT01335087 (clinicaltrials.gov)., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

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.

Introduction: The aim of this study is to assess the effect of obstructive sleep apnea syndrome (OSAS) severity on leptin levels in children., Patients and Methods: Children with habitual snoring underwent overnight polysomnography. Fasting venous blood samples were obtained between 8 AM and 9 AM, following the night of the sleep study. Children with an apnea-hypopnea index of ≥ 5/h were included in the moderate-to-severe OSAS group while those with an apnea-hypopnea index of < 5/h formed the mild OSAS/primary snoring group., Result: 47 children (51% male and 49% female; mean age 7.8 ± 2.6 years) were recruited. Twenty seven participants were diagnosed with moderate-to-severe OSAS, and twenty children who had AHI < 5 were included in the mild OSAS/primary snoring. The two groups did not differ regarding age, gender and body mass index z score (p> 0.05). Furthermore there were no differences in log serum leptin levels (p= 0.749). Log serum leptin levels correlated with the BMI z score in the whole study group (p= 0.001; r= 0.499) but they were not associated with apnea-hypopnea index, mean and lowest oxygen saturation during sleep., Conclusions: Serum leptin levels are affected by adiposity but not by OSAS severity among children with habitual snoring.

Objective/background: Obstructive sleep apnea (OSA) is a common disorder, affecting over 100 million adults. Untreated OSA leads to serious health consequences and perturbations in endocrine, immune, inflammatory, and metabolic systems. Study objectives are to evaluate the association between OSA and biomarkers, and to test the hypothesis that a combination of markers may be useful in screening for OSA., Patients/methods: A multicenter trial was conducted enrolling symptomatic male patients with suspected OSA. All subjects underwent in-laboratory overnight polysomnography. A non-symptomatic control group was also obtained. Eleven biomarkers were tested: HbA1c, CRP, EPO, IL-6, uric acid, cortisol, hGH, prolactin, testosterone, DHEA (Beckman Coulter UniCel DxC 600i Synchron® Access® Clinical Systems), IGF-1., Results: 73 male subjects were enrolled; 26 had moderate/severe OSA. ROC curve analysis showed HbA1c, CRP, EPO, IL-6, and Uric Acid (AUCs: 0.76, 0.73, 0.65, 0.65, 0.61) were superior to the Epworth Sleepiness Scale (AUC: 0.52). Concurrent elevation of HbA1c and CRP provide even greater predictive power. A combination of elevated HbA1c, CRP, and EPO provided 0.08 increase in AUC (0.84 [0.75 - 0.94]) over individual markers (p<0.05), with high sensitivity (85%), and specificity (79%) for moderate/severe OSA., Conclusions: OSA induces characteristic endocrine, immune, inflammatory, and metabolic disturbances that can be detected with blood biomarkers. These biomarkers are superior to standard screening questionnaires. Various clusters of these biomarkers have an even greater association with OSA and thus may represent physiologic signatures of the disorder that may have value in initial screening for OSA as well as for follow-up of therapy response., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Surfactant proteins B and C are mainly synthesized, secreted by alveolar type II cells, and affected by hypoxia and mechanical stretches. We hypothesized that their serum levels might be altered by intermittent hypoxia and swing of intrathoracic pressure of obstructive sleep apnea (OSA)., Methods: Consecutive 140 middle-aged males, suspicious of OSA determined by polysomnography, were studied. Surfactant proteins B and C were determined by ELISA., Results: Surfactant protein B (41.39 ± 6.01 vs 44.73 ± 7.62 ng/L, p = 0.005), not C (32.60 ± 6.00 vs 32.43 ± 6.44 ng/L, p = 0.61), significantly lowered in moderate to severe OSA subjects than in non to mild OSA subjects. Severity of OSA is inversely correlated with serum surfactant protein B. Adjusting age, body mass index, and smoking history, compared to subjects with surfactant protein B (SP-B) ≥43.35 ng/L, those with SP-B <43.35 ng/L showed significantly increased 1.528-fold risk for moderate to severe OSA (p = 0.009), whereas no association between surfactant protein C and OSA was observed. Prevalence of moderate to severe OSA in lower SP-B group is higher than that in higher SP-B group (62.7 vs 38.4 %, p = 0.003). Serial and parallel tests on Epworth sleep scale (ESS) and SP-B evaluation can be complementary and prove helpful with high specificity (94.44 %) and sensitivity (84.48 %) to detect moderate to severe OSA., Conclusions: Serum surfactant protein B, rather than C, is decreased in some individuals with moderate to severe OSA, compared to non to mild OSA subjects. Serum surfactant protein B might be a potential biomarker to diagnose OSA.

Objective: To investigate the level of endothelial cell specific molecule-1 (endocan) in obstructive sleep apnea (OSA)., Methods: Study group included subjects with OSA. Control group included subjects who had no OSA on polysomnography and nonobese healthy subjects from population who had no OSA symptoms. Endocan levels of OSA and non-OSA subjects were compared., Results: Totally 106 individuals (63 OSA, 43 non-OSA) were included. Endocan levels were higher in OSA subjects than controls (1.25 ± 0.4 ng/ml vs 0.93 ± 0.3 ng/ml, p < 0.001). Endocan levels were correlated with BMI (r = 0.456, p < 0.001) and daytime PaO2 (r = -0.266, p < 0.042). In linear regression analysis there was no factor related to endocan level., Conclusion: Serum endocan is significantly higher in OSA. Further studies should be performed to better understand the relationship between endocan and OSA.

Background: Positive airway pressure (PAP) reverses obstructive sleep apnea (OSA)-related hypoxia and restores slow wave sleep (SWS). Insulin-like growth factor 1 (IGF-1) is a neuropeptide that facilitates the repair of neurons from hypoxia and improves sleep regulation. IGF-1 concentrations are lower in OSA, and likely increase following PAP treatment; however, this relationship has not yet been determined in a younger cohort of OSA patients., Methods: This was a prospective, observational pilot study of 58 young men, who were diagnosed with OSA and provided PAP as an intervention. Adherence to PAP treatment over 3 months was objectively measured, as well as changes in the apnea-hypopnea index (AHI). Serum concentrations of IGF-1and C-reactive protein (CRP) were measured and correlated with PAP adherence., Results: IGF-1 concentrations at baseline were similar between PAP adherent 55.5 ± 34.4 ng/ml and PAP nonadherent participants 61.2 ± 27.1 ng/ml (p = 0.4), with the overall mean IGF-1 concentration of 59.0 ± 29.9 ng/ml. At follow-up, adherent participants had concentrations of IGF-1 that were significantly higher 128 ± 59.5 ng/ml compared to nonadherent participants 86.0 ± 47.4 ng/ml (p < 0.01). Increases in IGF-1 concentrations were significantly associated with reductions in AHI (Spearman's rho = -0.409, p = 0.015). Conversely, CRP concentrations did not differ between baseline and follow-up measurements in either group., Conclusions: Adherence to PAP treatment leads to significant increases in IGF-1 concentrations in young men with OSA. While an objective measure of adherence exists, PAP usage does not allow for measure of sleep improvement. IGF-1 may serve as a potential biomarker for the efficacy of PAP therapy on improved sleep.

There is conflicting evidence whether intermittent hypoxia in obstructive sleep apnoea (OSA) influences oxidative stress. We hypothesised that withdrawal of continuous positive airway pressure (CPAP) from patients with OSA would raise markers of oxidative stress.59 patients with CPAP-treated moderate-to-severe OSA (oxygen desaturation index (ODI) >20 events·h(-1)) were randomised 1:1 to either stay on CPAP (n=30) or change to sham CPAP (n=29) for 2 weeks. Using samples from two similar studies at two sites, we measured early morning blood malondialdehyde (MDA, a primary outcome in one study and a secondary outcome in the other), lipid hydroperoxides, total antioxidant capacity, superoxide generation from mononuclear cells and urinary F2-isoprostane. We also measured superoxide dismutase as a marker of hypoxic preconditioning. "Treatment" effects (sham CPAP versus CPAP) were calculated via linear regression.Sham CPAP provoked moderate-to-severe OSA (mean ODI 46 events·h(-1)), but blood markers of oxidative stress did not change significantly (MDA "treatment" effect (95% CI) -0.02 (-0.23 to +0.19) μmol·L(-1)). Urinary F2-isoprostane fell significantly by ~30% (-0.26 (-0.42 to -0.10) ng·mL(-1)) and superoxide dismutase increased similarly (+0.17 (+0.02 to +0.30) ng·mL(-1)).We found no direct evidence of increased oxidative stress in patients experiencing a return of their moderate-to-severe OSA. The fall in urinary F2-isoprostane and rise in superoxide dismutase implies that hypoxic preconditioning may have reduced oxidative stress., (Copyright ©ERS 2015.)

Background: Obstructive sleep apnea (OSA) has been associated with adverse fetal outcomes in some studies. Second trimester Down syndrome screening markers reflect fetal and fetoplacental wellbeing. We aimed to compare markers of fetal and feto-placental wellbeing in women with OSA and low risk controls., Methods: A retrospective case-control study of pregnant women with OSA and available second trimester markers was performed. Controls were screened for sleep disordered breathing (SDB) at the time of delivery using a questionnaire. Women at low risk for OSA were selected. Marker levels were adjusted for gestational age and race and reported as multiples of median and later adjusted for body mass index (BMI)., Results: Twenty-four OSA cases and 166 controls were identified. Women with OSA had a higher mean BMI when compared to controls (37.1 ± 12.7 versus 24.1 ± 5.1, p = 0.03). Estriol (uE3) multiples of the median (MoM) levels were lower in women with OSA compared to controls, even after adjusting for BMI, 0.74 (interquartile range (IQR) 0.45) versus 1.06 (IQR 0.38), respectively, p = 0.026. Once adjusted for BMI, alpha feto-protein (AFP) MoM levels were no longer significantly different in women with OSA compared to controls., Conclusion: OSA is associated with reduced serum uE3 levels, independently of BMI, possibly indicating fetal distress.

Aims: Obstructive sleep apnea (OSA) is associated with placenta-mediated adverse clinical outcomes. We aimed at comparing placenta-secreted proteins, such as first and second trimester Down syndrome screening markers which have been linked to preeclampsia, and markers of angiogenesis in pregnant women with OSA, and pregnant controls at low risk for OSA., Methods: A case-control study of pregnant women with OSA and controls at low risk for OSA was performed. Levels of first and second trimester markers were reported as multiple of median (MoM), and adjusted for body mass index (BMI). Stored samples were tested for markers of angiogenesis and adjusted for gestational age, BMI, and chronic hypertension., Results: A total of 24 women with OSA and 166 controls had screening markers. BMI was higher in cases compared to controls, P=0.01. MoM levels of placenta associated plasma protein-A (PAPP-A) were significantly lower in cases versus controls, even after adjusting for BMI (0.52 IQR 0.48 vs. 1.01 IQR 0.63, P=0.009). The ratio of soluble vascular endothelial growth factor receptor 1 to placental growth factor was significantly higher in cases than controls, even after adjusting for confounders (4.42 IQR 2.52 vs. 2.93 IQR 2.01, P=0.009)., Conclusion: Circulating placenta-secreted glycoproteins and markers of angiogenesis are altered in pregnant women with OSA.

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia during sleep. We tested the hypothesis that nocturnal myocardial ischemia is detectable by ST segment depression and elevation of high sensitive troponin T (hsTrop T) and B-type natriuretic peptide (NT-proBNP) in patients with OSA and coexisting coronary artery disease (CAD). Twenty-one patients with OSA and CAD and 20 patients with OSA alone underwent in-hospital polysomnography. Blood samples for hsTrop T and NT-proBNP measurements were drawn before and after sleep. ST segment depression was measured at the time of maximum oxygen desaturation during sleep. The apnea-hypopnea-index (AHI), oxygen saturation nadir, and time in bed with oxygen saturation of ≤80% were similar in both groups. Levels of hsTrop T and NT-proBNP did not differ significantly before and after sleep but NT-proBNP levels were significantly higher in patients suffering from OSA and CAD compared to patients with OSA alone. No significant ST depression was found at the time of oxygen saturation nadir in either group. Despite the fact that patients with untreated OSA and coexisting CAD experienced severe nocturnal hypoxemia, we were unable to detect myocardial ischemia or myocyte necrosis based on significant ST segment depression or elevation of hsTrop T and NT-proBNP, respectively.

Objective: Copeptin is a precursor of AVP, an antidiuretic hormone, plays a pivotal role in the maintenance of cardiovascular homeostasis. Obstructive sleep apnea syndrome (OSAS) is related to cardiovascular disease. We sought to evaluate the serum copeptin levels in newly diagnosed prehypertensive patients with OSAS., Patients and Methods: Eighty-four prehypertensive patients were evaluated using polysomnography and were divided into two groups, an OSAS (n = 41) group and a control (n = 43) group. Serum copeptin levels were measured using the ELISA method., Results: Copeptin levels were significantly higher in the OSAS group compared to the control group (146 [93-739] pg/ml vs. 111 [33-253] pg/ml, respectively, p < 0.001). A regression analysis revealed that the apnea hypopnea index (AHI) and the lowest SpO2 were related to serum copeptin levels (unstandardized β = 1.02 ± 0.40, p = 0.014 and unstandardized β = -3.1 ± 0.9, p = 0.048 respectively)., Conclusions: According to the results of our study, serum copeptin levels are higher in the prehypertensive patients with OSAS compared to those in the control group. Therefore, in assessing the severity of OSAS, serum copeptin levels can be a candidate for a biochemical marker in addition to polysomnographic findings.

Background: Oxidative stress has a central role in the pathophysiology of obstructive sleep apnea syndrome (OSAS). The DJ-1 protein functions as a sensor of oxidative stress, acting both as a reactive oxygen species scavenger (ROS) and an antioxidative response regulator. The aim of our study is to determine the serum levels of DJ-1 in OSAS patients and assess possible correlations with their clinical, demographical, and biochemical characteristics., Methods: The study included 120 subjects from the Sleep Disorder Laboratory of the University Hospital of Thessaly (100 males vs 20 females, mean age 48±10, Apnea-Hypopnea Index (AHI)>5 episodes per hour of sleep). Subjects underwent full-night polysomnography (PSG) followed by morning blood sampling. Serum DJ-1 levels were determined via ELISA kits. Statistical analysis was performed using SPSS 19., Results: The median DJ-1 levels were 56.7 ng/mL (IQR, 34.9-99.3 ng/mL). Statistically significant correlations were detected between DJ-1's levels and AHI (Spearman's rho=0.189, P=0.04), Desaturation Index (DI; Spearman's rho=0.239, P=0.012), and serum low-density lipoprotein (LDL) (Spearman's rho=-0.205, P=0.042)., Conclusions: DJ-1 may be a useful biomarker in OSAS due to its correlations with AHI and DI. The correlation with serum LDL warrants further investigation regarding possible implications in OSAS patients' cardiovascular comorbidities.

Leptin, a pleiotropic protein hormone produced mainly by fat cells, regulates metabolic activity and many other physiological functions. The intrinsic circadian rhythm of blood leptin is modulated by gender, development, feeding, fasting, sleep, obesity, and endocrine disorders. Hyperleptinemia is implicated in leptin resistance. To determine the specificity and sensitivity of leptin concentrations in sleep disorders, we summarize here the alterations of leptin in four conditions in animal and human studies: short duration of sleep, sleep fragmentation, obstructive sleep apnea (OSA), and after use of continuous positive airway pressure (CPAP) to treat OSA. The presence and causes of contradictory findings are discussed. Though sustained insufficient sleep lowers fasting blood leptin and therefore probably contributes to increased appetite, obesity and OSA independently result in hyperleptinemia. Successful treatment of OSA by CPAP is predicted to decrease hyperleptinemia, making leptin an ancillary biomarker for treatment efficacy. Current controversies also call for translational studies to determine how sleep disorders regulate leptin homeostasis and how the information can be used to improve sleep treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: Copeptin, the C-terminal fragment of antidiuretic hormone (ADH), is a new biomarker that has been found to be elevated in several cardiovascular disorders and is related with prognosis. Patients with obstructive sleep apnea demonstrate a tendency to develop coronary and cerebral atherosclerotic disease. Our aim was to investigate copeptin levels in untreated new diagnosed obstructive sleep apnea patients without manifest cardiovascular disorders in order to determine whether copeptin could be used as a biomarker in this group., Methods: A total of 60 patients with obstructive sleep apnea, diagnosed with polysomnography, and 23 healthy volunteers were enrolled into this study. Blood samples were collected after overnight fasting, and copeptin level was measured with an enzyme immunoassay method., Results: Patients with obstructive sleep apnea had a higher incidence of hypertension and body mass index but lower serum copeptin level (0.48 ± 0.24. vs. 0.64 ± 0.28 ng/ml, p = 0.007) compared with the healthy controls. There was no significant difference regarding to serum copeptin levels between the moderate (n = 13) and severe (n = 47) obstructive sleep apnea patients (0.42 ± 0.18 vs. 0.49 ± 0.26 ng/ml, p = 0.409)., Conclusions: Rather than reflecting a reduced risk for cardiovascular disorders, we consider that reduced copeptin level is related with disturbed ADH secretion in obstructive sleep apnea patients. Therefore, it would not be advisable to measure copeptin levels in obstructive sleep apnea patients to determine cardiovascular risk, while this marker could be valuable to demonstrate impairment in ADH regulation in this patient group.

Study Objectives: Obstructive sleep apnea (OSA) has been linked to and is associated with increased cardiovascular and cerebrovascular morbidity. Ongoing inflammatory responses play an important role in this association. Multiple small size studies addressing the profile of the inflammatory markers in OSA are available therefore we performed a meta-analysis., Methods: Systematic review of medical literature was conducted using PubMed, Cochrane, and EMBASE databases from 1968 to 2011 by utilizing the key words obstructive sleep apnea, C-Reactive protein, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and Selectins. Inclusion criteria were: full text English articles; studies with adult population; reported values for at least one of the markers of interest; with at least two separate groups (subjects with OSA and control group); OSA was defined as AHI of ≥ 5/h., Results: Five hundred and twelve studies were reviewed for inclusion with 51 studies pooled for analysis (30 studies for CRP, 19 studies for TNF-α, 8 studies for ICAM, 18 studies for IL-6, six studies for VCAM and 5 studies for Selectins). The levels of inflammatory markers were higher in patients with OSA compared to control group. Standardized pooled Mean differences were calculated to be 1.77 for CRP, 1.03 for TNF-α, 2.16 for IL-6, 4.22 for IL-8, 2.93 for ICAM, 1.45 for Selectins and 2.08 for VCAM., Conclusions: In this meta-analysis, the levels of systemic inflammatory markers were found to be higher in OSA patients compared to control subjects.