Elevation of CD40/CD40L Inflammatory Pathway Molecules in Carotid Plaques from Moderate-and-Severe Obstructive Sleep Apnea Patients.
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ABSTRACT:
SUBMITTER: Migacz E
PROVIDER: S-EPMC8224789 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:BackgroundLittle is known about whether the overlap syndrome (OS) combining features of chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome increases the risk of stroke associated with COPD itself.MethodsWe prospectively studied 74 COPD patients and 32 subjects without lung disease. Spirometry and cardiorespiratory polygraphy were used to assess the pulmonary function of the study population and ultrasound measurements of intima media thickness (IMT) as well as the volume of plaques in both carotid arteries were also evaluated.ResultsPolygraphic criteria of OS were met in 51% of COPD patients. We found that 79% of patients with OS and 50% of COPD patients without OS had atherosclerotic plaques in the left carotid artery (p = 0.0509). Interestingly, the mean volume of atherosclerotic plaques was significantly higher in the left carotid artery of COPD patients with OS (0.07 ± 0.02 ml) than in those without OS (0.04 ± 0.02 ml, p = 0.0305). However, regardless of the presence of OS, no significant differences were observed in both presence and volume of atherosclerotic plaques in the right carotid artery of COPD patients. Adjusted-multivariate linear regression revealed age, current smoking and the apnea/hypopnea index (OR = 4.54, p = 0.012) as independent predictors of left carotid atherosclerotic plaques in COPD patients.ConclusionsThis study suggests that the presence of OS in COPD patients is associated with larger left carotid atherosclerotic plaques, indicating that OS might be screened in all COPD patients to identify those with higher risk of stroke.
| S-EPMC10070750 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is associated with cardiometabolic diseases. Telomere shortening is linked to hypertension, diabetes mellitus, and cardiovascular diseases. Because these conditions are highly prevalent in OSA, we hypothesized that telomere length (TL) would be reduced in OSA patients. We identified 106 OSA and 104 non-OSA subjects who underwent polysomnography evaluation. Quantitative PCR was used to measure telomere length in genomic DNA isolated from peripheral blood samples. The association between OSA and TL was determined using unadjusted and adjusted linear models. There was no difference in TL between the OSA and non-OSA (control) group. However, we observed a J-shaped relationship between TL and OSA severity: the longest TL in moderate-to-severe OSA [4,918?±?230 (SD) bp] and the shortest TL in mild OSA (4,735?±?145 bp). Mean TL in moderate-to-severe OSA was significantly longer than in the control group after adjustment for age, sex, body mass index, hypertension, dyslipidemia, and depression (??=?96.0, 95% confidence interval: 15.4-176.6, P = 0.020). In conclusion, moderate-to-severe OSA is associated with telomere lengthening. Our findings support the idea that changes in TL are not unidirectional processes, such that telomere shortening occurs with age and disease but may be prolonged in moderate-to-severe OSA.NEW & NOTEWORTHY Here, we show that moderate-to-severe obstructive sleep apnea is associated with longer telomeres, independent of age and cardiovascular risk factors, challenging the hypothesis that telomere shortening is a unidirectional process related to age/disease. A better understanding of the mechanisms underlying telomere dynamics may identify targets for therapeutic intervention in cardiovascular aging/other chronic diseases.
| S-EPMC5792204 | biostudies-other
Project description:Study objectiveTo investigate whether low levels of physical activity were associated with an increased occurrence of obstructive sleep apnea (OSA), OSA-related symptoms, and cardiometabolic risk.MethodsA case-control study design was used. OSA cases were patients referred to a sleep clinic for suspected OSA (n = 2,340). Controls comprised participants from the Busselton community (n = 1,931). Exercise and occupational activity were derived from questionnaire data. Associations were modelled using logistic and linear regression and adjusted for confounders.ResultsIn comparison with moderate exercise, the high, low, and nil exercise groups had an odds ratio (OR) for moderate-severe OSA of 0.6 (95% CI 0.5-0.8), 1.6 (95% CI 1.2-2.0), and 2.7 (95% CI 1.9-3.7), respectively. Relative to men in heavy activity occupations, men in medium, light and sedentary occupations had an OR for moderate-severe OSA of 1.7 (95% CI 1.1-2.5), 2.1 (95% CI 1.4-3.2), and 1.8 (95% CI 1.2-2.8), respectively. Relative to women in medium activity occupations, women in light and sedentary occupations had an OR for moderate-severe OSA of 4.2 (95% CI 2.6-7.2) and 3.5 (2.0-6.0). OSA patients who adequately exercised had lower: levels of doctor-diagnosed depression (p = 0.047); symptoms of fatigue (p < 0.0001); systolic (p = 0.015) and diastolic blood pressure (p = 0.015); and C-reactive protein (CRP) (p = 0.003).ConclusionsLow levels of physical activity were associated with moderate-severe OSA. Exercise in individuals with OSA is associated with lower levels of depression, fatigue, blood pressure and CRP.
| S-EPMC4582050 | biostudies-literature
Project description:ObjectiveInvestigate multilevel radiofrequency ablation (RFA) as an alternative therapy for patients with mild-to-moderate obstructive sleep apnea (OSA).Study designProspective, open-label, single-arm, nonrandomized clinical trial.SettingMulticenter academic and private clinics.MethodsPatients with mild-to-moderate OSA (apnea-hypopnea index [AHI] 10-30; body mass index ≤ 32) were treated with 3 sessions of office-based RFA to the soft palate and tongue base. The primary outcome was a change in the AHI and oxygen desaturation index (ODI 4%). Secondary outcomes included subjective sleepiness level; snoring level; and sleep-related quality of life.ResultsFifty-six patients were enrolled, with 43 (77%) completing the study protocol. Following 3 sessions of office-based RFA to the palate and base of the tongue, the mean AHI decreased from 19.7 to 9.9 (p = .001), while the mean ODI (4%) decreased from 12.8 to 8.4 (p = .005). Mean Epworth Sleepiness Scale scores declined from 11.2 (±5.4) to 6.0 (±3.5) (p = .001), while Functional Outcomes of Sleep Questionnaire scores improved from a mean of 14.9 at baseline to 17.4 (p = .001). The mean visual analog scale snoring scale was reduced from 5.3 (±1.4) at baseline to 3.4 (±1.6) at 6 months posttherapy (p = .001).ConclusionOffice-based, multilevel RFA of the soft palate and base of the tongue is a safe and effective treatment option with minimal morbidity for properly selected patients with mild-to-moderate OSA who are intolerant or refuse continuous positive airway pressure therapy.
| S-EPMC10046721 | biostudies-literature
Project description:Although previous studies have reported a facial expression classification deficit among adults with SDB, we do not know whether these findings can be generalized to children. In our study, children with sleep-disordered breathing (SDB) were divided into three groups: primary snoring (n = 51), mild obstructive sleep apnea (OSA) (n = 39), and moderate/severe OSA (n = 26). All participants, including 20 healthy controls, underwent an overnight polysomnography recording and the Emotional Expression Recognition Task. Psychosocial problems were evaluated using the parent-reported Strengths and Difficulties Questionnaire (SDQ). There was a borderline significant interaction between expression category and group on reaction times. Further analysis revealed that positive classification advantage (PCA) disappeared in the moderate/severe OSA group, whereas it persisted in the control, primary snoring, and mild OSA groups. Emotional symptoms were positively correlated with OAHI. In both the happy and sad conditions, RT was negatively related to age and body mass index (BMI) but was independent of the obstructive apnea-hypopnea index (OAHI), arterial oxygen (SaO2) and total sleep time. The accuracy of identifying a sad expression was negatively related to conduct problems. Children with moderate/severe OSA exhibited dysfunction in facial expression categorization, which could potentially affect social communication ability.
| S-EPMC9776404 | biostudies-literature
Project description:PURPOSE:The purpose of this study is to test the effects of a mild degree of head-of-bed elevation (HOBE) (7.5°) on obstructive sleep apnea (OSA) severity and sleep quality. METHODS:OSA patients were recruited from a single sleep clinic (Criciúma, Santa Catarina, Brazil). Following a baseline polysomnography (PSG), all patients underwent a PSG with HOBE (within 2 weeks). In addition, a subset of patients performed a third PSG without HOBE. RESULTS:Fifty-two patients were included in the study (age 53.2 ± 9.1 years; BMI 29.6 ± 4.8 kg/m2, neck circumference 38.9 ± 3.8 cm, and Epworth Sleepiness Scale 15 ± 7). Compared to baseline, HOBE significantly decreased the apnea-hypopnea index (AHI) from 15.7 [11.3-22.5] to 10.7 [6.6-16.5] events/h; p < 0.001 and increased minimum oxygen saturation from 83.5 [77.5-87] to 87 [81-90]%; p = 0.003. The sleep architecture at baseline and HOBE were similar. However, sleep efficiency increased slightly but significantly with HOBE (87.2 [76.7-90.7] vs 88.8 [81.6-93.3]; p = 0.005). The AHI obtained at the third PSG without HOBE (n = 7) returned to baseline values. CONCLUSIONS:Mild HOBE significantly improves OSA severity without interfering in sleep architecture and therefore is a simple alternative treatment to ameliorate OSA.
| S-EPMC5700252 | biostudies-literature
Project description:STUDY OBJECTIVE: We aimed to test the hypothesis that clinically suspected obstructive sleep apnea (OSA) independently predicts worse in-hospital outcome in patients with non-ST elevation acute coronary syndromes. DESIGN: At admission, individuals were evaluated for clinical probability of OSA by the Berlin Questionnaire. Primary cardiovascular endpoint was defined as the composite of death, nonfatal myocardial infarction, or refractory angina during hospitalization. SETTING: Coronary care unit. PATIENTS: There were 168 consecutive patients admitted with unstable angina or non-ST elevation acute myocardial infarction. MEASUREMENTS AND RESULTS: During a median hospitalization of 8 days, the incidence of cardiovascular events was 13% (12 deaths, 4 nonfatal myocardial infarctions, and 6 refractory anginas.) Incidence of the primary endpoint was 18% in individuals with high probability of OSA, compared with no events in individuals with low probability (P = 0.002). After logistic regression adjustment for the Global Registry of Acute Coronary Events (GRACE) risk score, anatomic severity of coronary disease, and hospital treatment, probability of OSA remained an independent predictor of events (odds ratio [OR] = 3.4; 95% confidence interval [CI] = 1.3 - 9.0; P = 0.015). Prognostic discrimination of the GRACE score, measured by a C-statistic of 0.72 (95% CI = 0.59-0.85), was significantly improved to 0.82 (95% CI = 0.73-0.92) after inclusion of OSA probability in the predictive model (P = 0.03). CONCLUSION: Considering the independent prognostic and incremental value of suspected OSA, this condition may represent an aggravating factor for patients with non-ST elevation acute coronary syndrome.
| S-EPMC3413801 | biostudies-other
Project description:Illumina MiSeq next generation sequencing chip was used to identify differentially expressed miRs by comparing peripheral blood mononuclear cell samples between OSA patients and healthy non-snorers.
2021-12-01 | GSE174245 | GEO