Complications Of Obstructive Sleep Apnea Research Articles

Recent progresses in gut microbiome mediates obstructive sleep apnea-induced cardiovascular diseases.

Obstructive sleep apnea (OSA) is a multifactorial sleep disorder with a high prevalence in the general population. OSA is associated with an increased risk of developing cardiovascular diseases (CVDs), particularly hypertension, and is linked to worse outcomes. Although the correlation between OSA and CVDs is firmly established, the mechanisms are poorly understood. Continuous positive airway pressure is primary treatment for OSA reducing cardiovascular risk effectively, while is limited by inadequate compliance. Moreover, alternative treatments for cardiovascular complications in OSA are currently not available. Recently, there has been considerable attention on the significant correlation between gut microbiome and pathophysiological changes in OSA. Furthermore, gut microbiome has a significant impact on the cardiovascular complications that arise from OSA. Nevertheless, a detailed understanding of this association is lacking. This review examines recent advancements to clarify the link between the gut microbiome, OSA, and OSA-related CVDs, with a specific focus on hypertension, and also explores potential health advantages of adjuvant therapy that targets the gut microbiome in OSA.

Chronic intermittent hypoxia-induced hypertension: the impact of sex hormones.

Obstructive sleep apnea, a common form of sleep-disordered breathing, is characterized by intermittent cessations of breathing that reduce blood oxygen levels and contribute to the development of hypertension. Hypertension is a major complication of obstructive sleep apnea that elevates the risk of end-organ damage. Premenopausal women have a lower prevalence of obstructive sleep apnea and cardiovascular disease than men and postmenopausal women, suggesting that sex hormones play a role in the pathophysiology of sleep apnea-related hypertension. The lack of protection in men and postmenopausal women implicates estrogen and progesterone as protective agents but testosterone as a permissive agent in sleep apnea-induced hypertension. A better understanding of how sex hormones contribute to the pathophysiology of sleep apnea-induced hypertension is important for future research and possible hormone-based interventions. The effect of sex on the pathophysiology of sleep apnea and associated intermittent hypoxia-induced hypertension is of important consideration in the screening, diagnosis, and treatment of the disease and its cardiovascular complications. This review summarizes our current understanding of the impact of sex hormones on blood pressure regulation in sleep apnea with a focus on sex differences.

Clinical features of sleep apnea syndrome and cognitive impairment in multiple sclerosis

Background: Complications of obstructive sleep apnea (OSA) have been reported in patients with multiple sclerosis (MS). Patients with sleep apnea syndrome (SAS) due to OSA also show cognitive decline, with similar clinical characteristics to that manifested in MS. SAS due to OSA is a treatable condition, and the associated cognitive decline is expected to improve. This study investigates clinical features of SAS in people living with MS and contribute to improve cognitive dysfunction of MS.Methods: A case-control study was conducted. Cognitive functions were evaluated by the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test 2 (PASAT-2) and 3 (PASAT-3). The Respiratory Event Index (REI) was measured using Out of Center Sleep Testing (OCST). We defined subjects with REI ≥ 5 as OSA and divided participants into two groups with or without SAS due to OSA. Cognitive and respiratory characteristics were statistically compared between patients with MS and healthy controls.Results: We enrolled 67 people living with MS and 31 age- and sex-matched controls. OCST detected OSA in people living with MS and controls, and the prevalence rates were 28.4 % and 25.8 %, respectively. REI values (5.2 ± 7.9 vs 3.9 ± 5.2, p = 0.509) and number of participants with REI ≥ 5 (19 vs 8, p = 0.793) were similar between the MS and control group. The SDMT, PASAT-2, and PASAT-3 scores were significantly lower in the MS group than the control group (p < 0.001, p = 0.001, and p < 0.001, respectively). The interaction effect of MS and SAS on cognitive function was not significant in the SDMT (p = 0.078), but in the PASAT-2 (p = 0.043) and PASAT-3 (p = 0.020).Conclusion: This study revealed the prevalence rates of SAS in Japanese people living with MS and the usefulness of OCST for detection of SAS. This study also revealed that concomitant SAS can facilitate cognitive decline in people living with MS. These findings suggest that an appropriate intervention for OSA can be beneficial for people living with MS with cognitive decline.

The role of microRNAs in pathophysiology and diagnostics of metabolic complications in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) is one of the most common sleep disorders, which is characterized by recurrent apneas and/or hypopneas occurring during sleep due to upper airway obstruction. Among a variety of health consequences, OSA patients are particularly susceptible to developing metabolic complications, such as metabolic syndrome and diabetes mellitus type 2. MicroRNAs (miRNAs) as epigenetic modulators are promising particles in both understanding the pathophysiology of OSA and the prediction of OSA complications. This review describes the role of miRNAs in the development of OSA-associated metabolic complications. Moreover, it summarizes the usefulness of miRNAs as biomarkers in predicting the aforementioned OSA complications.

Adenotonsillectomy-related changes in systemic inflammation among children with obstructive sleep apnea.

Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined. This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA. Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI ( r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) ( r = 0.34), change in tonsil size and % change in and IL-10 ( r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) ( r = 0.30), and % change in CCL5 and % change in AHI ( r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: β = 16.672, standard error = 8.274, p = 0.048). These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5.

Neurotrophins in the Neuropathophysiology, Course, and Complications of Obstructive Sleep Apnea—A Narrative Review

Obstructive sleep apnea (OSA) is a disorder characterized by chronic intermittent hypoxia and sleep fragmentation due to recurring airway collapse during sleep. It is highly prevalent in modern societies, and due to its pleiotropic influence on the organism and numerous sequelae, it burdens patients and physicians. Neurotrophins (NTs), proteins that modulate the functioning and development of the central nervous system, such as brain-derived neurotrophic factor (BDNF), have been associated with OSA, primarily due to their probable involvement in offsetting the decline in cognitive functions which accompanies OSA. However, NTs influence multiple aspects of biological functioning, such as immunity. Thus, extensive evaluation of their role in OSA might enlighten the mechanism behind some of its elusive features, such as the increased risk of developing an immune-mediated disease or the association of OSA with cardiovascular diseases. In this review, we examine the interactions between NTs and OSA and discuss their contribution to OSA pathophysiology, complications, as well as comorbidities.

Construction of a mitochondrial dysfunction related signature of diagnosed model to obstructive sleep apnea.

Background: The molecular mechanisms underlying obstructive sleep apnea (OSA) and its comorbidities may involve mitochondrial dysfunction. However, very little is known about the relationships between mitochondrial dysfunction-related genes and OSA. Methods: Mitochondrial dysfunction-related differentially expressed genes (DEGs) between OSA and control adipose tissue samples were identified using data from the Gene Expression Omnibus database and information on mitochondrial dysfunction-related genes from the GeneCards database. A mitochondrial dysfunction-related signature of diagnostic model was established using least absolute shrinkage and selection operator Cox regression and then verified. Additionally, consensus clustering algorithms were used to conduct an unsupervised cluster analysis. A protein-protein interaction network of the DEGs between the mitochondrial dysfunction-related clusters was constructed using STRING database and the hub genes were identified. Functional analyses, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA), were conducted to explore the mechanisms involved in mitochondrial dysfunction in OSA. Immune cell infiltration analyses were conducted using CIBERSORT and single-sample GSEA (ssGSEA). Results: we established mitochondrial dysfunction related four-gene signature of diagnostic model consisted of NPR3, PDIA3, SLPI, ERAP2, and which could easily distinguish between OSA patients and controls. In addition, based on mitochondrial dysfunction-related gene expression, we identified two clusters among all the samples and three clusters among the OSA samples. A total of 10 hub genes were selected from the PPI network of DEGs between the two mitochondrial dysfunction-related clusters. There were correlations between the 10 hub genes and the 4 diagnostic genes. Enrichment analyses suggested that autophagy, inflammation pathways, and immune pathways are crucial in mitochondrial dysfunction in OSA. Plasma cells and M0 and M1 macrophages were significantly different between the OSA and control samples, while several immune cell types, especially T cells (γ/δ T cells, natural killer T cells, regulatory T cells, and type 17T helper cells), were significantly different among mitochondrial dysfunction-related clusters of OSA samples. Conclusion: A novel mitochondrial dysfunction-related four-gen signature of diagnostic model was built. The genes are potential biomarkers for OSA and may play important roles in the development of OSA complications.

Cardiovascular Complications of Obstructive Sleep Apnea in the Intensive Care Unit and Beyond.

Obstructive sleep apnea (OSA) is a common disease with a high degree of association with and possible etiological factor for several cardiovascular diseases. Patients who are admitted to the Intensive Care Unit (ICU) are incredibly sick, have multiple co-morbidities, and are at substantial risk for mortality. A study of cardiovascular manifestations and disease processes in patients with OSA admitted to the ICU is very intriguing, and its impact is likely significant. Although much is known about these cardiovascular complications associated with OSA, there is still a paucity of high-quality evidence trying to establish causality between the two. Studies exploring the potential impact of therapeutic interventions, such as positive airway pressure therapy (PAP), on cardiovascular complications in ICU patients are also needed and should be encouraged. This study reviewed the literature currently available on this topic and potential future research directions of this clinically significant relationship between OSA and cardiovascular disease processes in the ICU and beyond.

MP38-19 PREVALENCE OF TESTOSTERONE DEFICIENCY AND SECONDARY POLYCYTHEMIA IN MEN WITH OBSTRUCTIVE SLEEP APNEA

You have accessJournal of UrologyCME1 May 2022MP38-19 PREVALENCE OF TESTOSTERONE DEFICIENCY AND SECONDARY POLYCYTHEMIA IN MEN WITH OBSTRUCTIVE SLEEP APNEA Chase Carto, Sirpi Nackeeran, and Ranjith Ramasamy Chase CartoChase Carto More articles by this author , Sirpi NackeeranSirpi Nackeeran More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002592.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Secondary polycythemia is a well-known complication of obstructive sleep apnea (OSA), a disorder that increases in incidence with age. Similarly, increased recognition of low testosterone and its associated symptoms in aging men has led to increased administration of testosterone replacement therapy (TRT), which has also been associated with secondary polycythemia. We hypothesized that given the common association of aging with OSA and testosterone deficiency, a significant percentage of men with OSA would carry concurrent diagnoses of testosterone deficiency and secondary polycythemia. The objective of this study was to investigate the epidemiology of men with OSA, secondary polycythemia, and testosterone deficiency in men using a large electronic health record network. METHODS: We performed a real-time search for adult men (18+) with a diagnosis of obstructive sleep apnea (ICD-10-CM G47.33) in the TriNetX network, which provides health record data for more than 75 million patients from 48 healthcare organizations. This cohort was used to separately identify men with testosterone deficiency, as defined by those with a diagnosis of testicular dysfunction or hypofunction (ICD-10-CM E29, E29.1), and secondary polycythemia (ICD-10-CM D75.1). Lastly, we queried the network for men with all three diagnoses: OSA, testosterone deficiency, and secondary polycythemia. All men with diagnosis of polycythemia vera or familial erythrocytosis were removed from the analysis to account for men with concurrent primary polycythemia. RESULTS: A total of 1,166,640 men with a diagnosis of OSA were identified in the network. Mean age of men with OSA was 61 [46 – 76]. Among men with OSA, 6.0% of men had testosterone deficiency (TT <300ng/dL), and 1.3% of men had associated polycythemia (Hct >52%). Interestingly, only 3,562 (0.3%) of men in the network had all three diagnoses of obstructive sleep apnea, testosterone deficiency, and secondary polycythemia. Strengths of this study include use of a large and heterogenous study population and adjustment for other causes of polycythemia. Limitations include lack of data on chronology of diagnoses, inconsistent data recording, and missing data. CONCLUSIONS: In a large, cross-sectional, multicenter electronic health record study, we found that 6.0% of men with OSA will have testosterone deficiency. Reassuringly, only 0.3% of men carry all diagnoses of obstructive sleep apnea, testosterone deficiency, and secondary polycythemia. Nevertheless, men with OSA who receive TRT warrant close follow-up for potentially dangerous increases in hematocrit when considering treatment for testosterone deficiency. Source of Funding: This work was supported by National Institutes of Health Grant R01 DK130991 and the Clinician Scientist Development Grant from the American Cancer Society to Ranjith Ramasamy © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e625 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chase Carto More articles by this author Sirpi Nackeeran More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF DownloadLoading ...

Role of epigenetic abnormalities and intervention in obstructive sleep apnea target organs.

Obstructive sleep apnea (OSA) is a common condition that has considerable impacts on human health. Epigenetics has become a rapidly developing and exciting area in biology, and it is defined as heritable alterations in gene expression and has regulatory effects on disease progression. However, the published literature that is integrating both of them is not sufficient. The purpose of this article is to explore the relationship between OSA and epigenetics and to offer better diagnostic methods and treatment options. Epigenetic modifications mainly manifest as post-translational modifications in DNA and histone proteins and regulation of non-coding RNAs. Chronic intermittent hypoxia-mediated epigenetic alterations are involved in the progression of OSA and diverse multiorgan injuries, including cardiovascular disease, metabolic disorders, pulmonary hypertension, neural dysfunction, and even tumors. This article provides deeper insights into the disease mechanism of OSA and potential applications of targeted diagnosis, treatment, and prognosis in OSA complications.

Clinical and polysomnographic characteristics in adults referred to the sleep laboratory: a single-center study.

Background: Polysomnography is the gold standard diagnostic method for obstructive sleep apnea syndrome, and on-time treatment can help prevent further complications of obstructive sleep apnea. However, polysomnography is associated with some difficulties for the patients and physicians, which hinder its application. This study aimed to evaluate the clinical features and polysomnography findings of patients with obstructive sleep apnea.Methods: Data were retrospectively collected from polysomnography studies at the Sleep Laboratory of Namazi Hospital, Shiraz, Iran, from February 2013 to December 2017. Polysomnography was performed for any patients suspected of obstructive sleep apnea. The researcher reviewed the data extracted and selected the essential clinical features for the statistical analysis. The association of variables with the polysomnography findings was analyzed.Results: Significant associations were observed between the following factors and severity of obstructive sleep apnea: older age (p = 0.01), snoring (p = 0.122), history of sleep disorders (p = 0.11), no sedatives before sleep (p = 0.039), nocturia (p = 0.001), apnea (p = 0.035), no smoking (p = 0.039), no substance abuse (p = 0.011), hypertension (p = 0.001), cardiac diseases (p = 0.025), and overweight and obesity (p < 0.001).Conclusion: Considering the concomitant occurrence of obstructive sleep apnea with obesity, hypertension, cardiac disease, snoring, and observed apnea, polysomnography is recommended in these patients before further assessments.

Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea.

Pulmonary hypertension (PH) is a rare yet serious complication of obstructive sleep apnea (OSA). Echocardiographic screening for PH is recommended in children with severe OSA, but the health care burden of universal screening is high. We sought to determine the prevalence of PH on echocardiogram among children with severe OSA and identify variables associated with a positive PH screen. Retrospective study of 318 children with severe OSA (obstructive apnea-hypopnea index ≥ 10 events/h) and echocardiogram within 1 year of polysomnogram. PH-positive echocardiogram was defined by peak tricuspid regurgitation velocity ≥ 2.5 m/s and/or 2 or more right-heart abnormalities suggestive of elevated pulmonary artery pressure. Patient characteristics and polysomnogram data were compared to identify factors associated with PH. Twenty-six children (8.2%; 95% confidence interval [CI] 5.4-11.8%) had echocardiographic evidence of PH. There was no difference in age, sex, body mass index, obstructive apnea-hypopnea index, or oxygenation indices between patients with and without PH. Sleep-related hypoventilation (end-tidal CO2 > 50 mmHg for > 25% of total sleep time) was present in 25% of children with PH compared with 6.3% of children without PH (adjusted prevalence ratio = 2.73; 95% CI 1.18-6.35). Forty-six percent of children (12/26) with PH had Down syndrome vs 14% (41/292) without PH (adjusted prevalence ratio = 3.11; 95% CI 1.46-6.65). There was a relatively high prevalence of PH on echocardiogram in our cohort of children with severe OSA. The findings of increased PH prevalence among children with sleep-related hypoventilation or Down syndrome may help inform the development of targeted screening recommendations for specific pediatric OSA populations. Maloney MA, Davidson Ward SL, Su JA, etal. Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1629-1637.

Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients-Possible Mechanisms Involved and Clinical Implication.

Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused by the collapse of the upper airways, which results in intermittent hypoxia and arousals during the night. The disorder is associated with a vast number of comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, and neurological complications. Due to abnormal sleep architecture, OSA patients are at high risk of circadian clock disruption, as has been reported in several recent studies. The circadian clock affects almost all daily behavioral patterns, as well as a plethora of physiological processes, and might be one of the key factors contributing to OSA complications. An intricate interaction between the circadian clock and hypoxia may further affect these processes, which has a strong foundation on the molecular level. Recent studies revealed an interaction between hypoxia-inducible factor 1 (HIF-1), a key regulator of oxygen metabolism, and elements of circadian clocks. This relationship has a strong base in the structure of involved elements, as HIF-1 as well as PER, CLOCK, and BMAL, belong to the same Per-Arnt-Sim domain family. Therefore, this review summarizes the available knowledge on the molecular mechanism of circadian clock disruption and its influence on the development and progression of OSA comorbidities.

Asystole due to vagal reflex in a patient with obstructive sleep apnea during anesthesia intubation with laryngoscope

Obstructive sleep apnea (OSA) is a serious sleep disorder. The complications of OSA are respiratory and cardiovascular events, including bradycardia, tachycardia, and even cardiac arrest. A 57-year-old female with OSA was vulnerable to vagal stimulation, developing severe bradycardia and asystole during general anesthesia while undergoing intubation with a conventional direct laryngoscope. This asystole case highlights the fact that anesthetized patients with OSA may experience increased parasympathetic activity (vagal tone) and vagal stimulation with consequent severe bradycardia and asystole. Atropine is recommended to resolve such conditions.

Obstructive sleep apnea in hypothyroidism.

Obstructive sleep apnea (OSA) and hypothyroidism are closely linked as hypothyroidism has been shown to lead to the development of OSA through multiple mechanisms. With the changing lifestyle patterns worldwide and increased prevalence of obesity, the burden of OSA has substantially increased. The association of OSA with hypothyroidism is essential to establish. If identified early, treatment of OSA and associated hypothyroidism can be done timely to minimize the potential harmful complications of OSA on all aspects of the patient's health. This study was done to find out the prevalence of OSA in hypothyroidism patients. It was a cross-sectional study, done over a period of 1 year in a tertiary care hospital. A total of 100 hypothyroidism patients were enrolled after taking written consent. All patients were subjected to STOP-Bang questionnaire and patient falling in intermediate-high risk (score3-8), were taken for overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). The Statistical Package for the Social Sciences version 21.0 statistical analysis software. Out of 100 patients, who underwent polysomnography, 74 (74%) cases had OSA (AHI ≥5). Out of total 74 OSA cases, 29 (39.2%) cases had mild OSA (AHI 5-14), 15 (20.3%) cases had moderate OSA (AHI 15-30), and 30 (40.5%) cases had severe OSA. The age of the study population ranged between 24 and 78 years and the mean age was 58.28 ± 11.22 years. The mean age of the patients in the OSA group (59.27 ± 11.17 years) was higher than the non-OSA group (55.46 ± 11.09 years). Majority (64%) of our cases were male, and the proportion of males was found to be higher than females in both the groups (OSA/non-OSA). The body mass index (BMI) of the OSA group was found to be statistically higher as compared to that of the non-OSA group (P = 0.040). The BMI was found to be higher in severe OSA, but it was not statistically significant (P = 0.128). The mean value of FT4 was lower and thyroid-stimulating hormone (TSH) was higher in the OSA group as compared with the non-OSA group. However, no significant association was found between FT4 and TSH values in both the groups. Out of 100 cases, 41 patients were treatment naïve with mean TSH value of 13.1 ± 7 and 59 were on treatment with mean TSH of 8.3 ± 4. Treatment-naïve patients had a statistically higher number (85.3%) of OSA cases in comparison to patients on treatment (66.1) (P = 0.030). Prevalence of OSA is quite high in hypothyroidism. Patients with hypothyroidism should be screened for OSA for early diagnosis, especially in individuals with higher BMI. Treatment of hypothyroidism reduces the prevalence of OSA.

Chapter 6 - Obstructive sleep apnea

Obstructive sleep apnea (OSA) is a disease that results from loss of upper airway muscle tone leading to upper airway collapse during sleep in anatomically susceptible persons, leading to recurrent periods of hypoventilation, hypoxia, and arousals from sleep. Significant clinical consequences of the disorder cover a wide spectrum and include daytime hypersomnolence, neurocognitive dysfunction, cardiovascular disease, metabolic dysfunction, respiratory failure, and pulmonary hypertension. With escalating rates of obesity a major risk factor for OSA, the public health burden from OSA and its sequalae are expected to increase, as well. In this chapter, we review the mechanisms responsible for the development of OSA and associated neurocognitive and cardiometabolic comorbidities. Emphasis is placed on the neural control of the striated muscles that control the pharyngeal passages, especially regulation of hypoglossal motoneuron activity throughout the sleep/wake cycle, the neurocognitive complications of OSA, and the therapeutic options available to treat OSA including recent pharmacotherapeutic developments.

The Association of Nephroblastoma Overexpressed (NOV) and Endothelial Progenitor Cells with Oxidative Stress in Obstructive Sleep Apnea.

Objective Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent hypoxia, chronic inflammation, and oxidative stress and is associated with cardiometabolic disease. Several biological substrates have been associated with OSA such as nephroblastoma overexpressed (NOV), endothelial progenitor cells (EPC), and circulating endothelial cells (CEC). Few studies have looked at the association of NOV with OSA while the EPC/CEC relationships with OSA are unclear. In this study, we hypothesize that (1) NOV is associated with the severity of OSA independent of BMI, identifying a protein that may play a role in the biogenesis of OSA complications, and (2) EPCs and CECs are also associated with the severity of OSA and are biomarkers of endothelial dysfunction in OSA. Methods 61 subjects underwent overnight polysomnography (PSG), clinical evaluation, and blood analysis for NOV, EPC, CEC, interleukin 6 (IL-6), and other potential biomarkers. Results NOV and EPCs were independently associated with the oxygen desaturation index (ODI) after adjusting for potential confounders including body mass index (BMI), age, and sex (NOV p = 0.032; EPC p = 0.001). EPC was also independently associated with AHI after adjusting for BMI, age, and sex (p = 0.017). IL-6 was independently associated with AHI, but not with ODI. Conclusion NOV and EPC levels correlate with the degree of OSA independent of BMI, indicating that these biomarkers could potentially further elucidate the relationship between OSA patients and their risk of the subsequent development of cardiovascular disease.

Opioids and obstructive sleep apnea.

Freire C, Sennes LU, Polotsky VY. Opioids and obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):647-652.

Sleep Apnea and Serum Serotonin Level Pre- and Post-PAP Therapy: A Preliminary Study.

IntroductionThe high prevalence of obstructive sleep apnea (OSA), which impairs quality of life for numerous patients and leads to various OSA complications, has contributed to the continued interest in this disorder. The role of serotonin (5-HT) in many physiological processes, studies on its connection with the circadian system, and relationship to changes in sleep architecture are insufficient to assess the interaction of this neurotransmitter with nocturnal hypoxia. The aim of this study was to determine changes in sleep patterns and serum serotonin levels before and after positive airway pressure (PAP) therapy in patients with OSA.MethodsThe study involved 30 OSA patients (27 men and 3 women) who were treated with PAP for 3 months. Polysomnography using the GRASS TELEFACTOR (USA) and blood collection were conducted before and after PAP courses. Determination of serum serotonin was performed by high-performance liquid chromatography (HPLC). PAP therapy was performed using an automatic Prisma 20A (Germany) continuous positive airway pressure (CPAP) device.ResultsThe use of PAP for 3 months revealed a significant improvement as measured by sleep data and serotonin levels (before: apnea index [AI] 17.2 eV/h, after: 2.4 eV/h p = 0.001; SpO2 < 90% − 45.7 min vs. 6.2 min p = 0.001; serotonin 20.3 ng/mL vs. 26.03 ng/mL p = 0.036].ConclusionOur results demonstrate an improvement in sleep patterns. There was an increase in serum serotonin levels in OSA patients following PAP therapy, which could be an effect of intermittent hypoxia decline, and could be used as criteria for the effectiveness of PAP and an improvement in sleep quality.

P060 Hypoxia-induced overexpression of Rev-Erb-alpha and NPAS2 proteins in obstructive sleep apnea patients - possible mechanism of DM2 development

Abstract Circadian clocks are endogenous coordinators of 24-hour behavioral and molecular rhythms, which disruption may be caused by obstructive sleep apnea (OSA). It is composed of a set of genes, function as activators (CLOCK, BMAL) or repressors (PER, CRY). Neuronal PAS Domain Protein 2 (NPAS2) can substitute CLOCK in its function. Orphan nuclear receptor (Rev-Erb-α) is another protein supporting the CLOCK-BMAL1 complex, forming the loop which helps to regulate their expression. There are studies suggesting the significant influence of circadian disruption mediated via NPAS2 and Rev-Erb-α on DM2 development. The aim of the study was to determine the role of NPAS2 and Rev-Erb-α in DM2 for OSA patients. All participants underwent polysomnography (PSG) examination. Based on apnea-hypopnea index accompanied by clinical data the recruited individuals (n=40) were assigned to one from 3 groups: OSA (severe OSA, no DM2; n=17), DM2 (severe OSA + DM2; n=7) and control group (no OSA, no DM2; n=16). Serum protein levels of Rev-Erb-α and NPAS2 were assessed with ELISA immunoassay. Analysis between the groups revealed the statistically significant difference only in NPAS2 protein level (p=0.037). Further post-hoc analysis revealed significant differences between OSA and the control group (p=0.017). Moreover, a statistically significant correlation between AHI and NPAS2 serum protein level was observed (r=-0.478, p=0.002). NPAS2 protein levels are associated with a number of apneas and hypopneas during the REM phase of sleep and might have a significant role in the development of OSA complications. However, further studies are needed to understand its role.