Serum miR-92a is Elevated in Children and Adults with Obstructive Sleep Apnea
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ABSTRACT: Background:
Obstructive Sleep Apnea (OSA) is a highly prevalent condition that is associated with several comorbidities including cardiovascular disease (CVD). Recent studies have revealed mixed results as to whether standard OSA therapy reverses CVD in adult patients. Thus, many advocate for earlier recognition of OSA induced CVD, as early as childhood, to prompt treatment antecedent to the onset of irreversible CVD. Here we investigated if the serum level of miR-92a, a known biomarker for CVD, can be used to identify patients with OSA in both children and adults. Methods:
Consecutive snoring patients undergoing polysomnography were recruited for determination of circulating miR-92a, in addition to inflammatory and metabolic profiles. We assessed whether circulating miR-92a was associated with OSA severity. Results:
Using two separate cohorts of adults (n=57) and children (n=13), we report a significant increase in the serum level of miR-92a in patients with severe OSA (p=0.021) and further demonstrate a significant correlation (Spearman rank correlation 0.308, p=0.010) with serum miR-92a levels and the apnea hypopnea index (AHI), a primary measure of OSA severity. Stepwise regression analysis revealed that serum miR-92a levels were independently associated with AHI (ß=0.332, p=0.003), age (ß=0.394, p=0.002) and LDL cholesterol levels (ß=0.368, p=0.004). Conclusion:
Our study is the first to establish that miR-92a is a useful biomarker for OSA severity in both children and adults. Given the canonical role of miR-92a on endothelial dysfunction, miR-92a may be useful to identify early onset CVD in OSA patients or stratify patient CVD risk to identify those that may benefit from earlier OSA treatment.
SUBMITTER: Gongol B
PROVIDER: S-EPMC7789821 | biostudies-literature | 2020 Jan
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
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Project description:PURPOSE:Ferritin is an intracellular iron storage protein and a marker of inflammation. Studies have shown that subjects with obstructive sleep apnea (OSA) have higher levels of circulating pro-inflammatory cytokines, but little is known about the association between ferritin and OSA. The aims of the study were to evaluate serum ferritin (S-Ferritin) levels in OSA patients compared to levels in the general population and also examine the effect of obesity level and treatment with positive airway pressure (PAP) on S-Ferritin levels. METHODS:The OSA subjects (n = 796) were part of the Icelandic Sleep Apnea Cohort. The control subjects (n = 637) were randomly chosen Icelanders who participated in an epidemiological study. Propensity score (PS) methodologies were employed to minimize selection bias and strengthen causal inferences when comparing non-randomized groups. S-Ferritin levels were measured and all participants answered the same detailed questionnaire about sleep and health. Only OSA patients underwent a sleep study and were re-invited for a 2-year follow-up. RESULTS:S-Ferritin levels were significantly higher in OSA males than controls (213.3 vs. 197.3 μg/L, p = 0.007). However, after adjusting for confounders and using our PS methodology, no significant difference was found. S-Ferritin levels were not correlated with severity of OSA, obesity level, or clinical symptoms. Also, no significant change in S-Ferritin levels was found with 2 years of PAP treatment. CONCLUSIONS:S-Ferritin levels are comparable in OSA patients and controls and do not change consistently with obesity level or PAP treatment in our sample.
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Project description:RationaleWe previously demonstrated that children with obstructive sleep apnea have increased blood pressure associated with changes in left ventricular mass index. Others have shown in adults that blood pressure variability is an important predictor of changes in left ventricular mass. The baroreflex system buffers blood pressure changes by varying heart rate. We have thus hypothesized that (1) baroreflex system gain is increased during sleep, improving blood pressure buffering; (2) children with obstructive sleep apnea lack this baroreflex gain increase; and (3) reduced blood pressure buffering results in exaggerated blood pressure variability that is associated with end-organ damage.ObjectivesCompare measures of left ventricular mass index and nighttime baroreflex gain of healthy children to those of children with obstructive sleep apnea.MethodsA total of 169 children (50 control subjects, 63 with mild obstructive sleep apnea, and 56 with severe obstructive sleep apnea) with a mean age of 9.9 years (+/-2.2) underwent echocardiography followed by polysomnography with continuous blood pressure measurement. Baroreflex gain was calculated in time and frequency domains.Measurements and main resultsHealthy children demonstrated a nighttime pattern of increasing baroreflex gain. Children with obstructive sleep apnea had decreased nighttime baroreflex gain compared with control subjects. Nighttime blood pressure and blood pressure variability were significantly correlated with left ventricular mass index.ConclusionsObstructive sleep apnea is associated with a decrease in nighttime baroreflex gain and an increase in blood pressure variability. This increase is correlated with changes in left ventricular mass index.
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Project description:Obstructive sleep apnea (OSA) is characterized by recurrent complete or partial obstruction of the upper airway. The prevalence is 1-4% in children aged between 2 and 8 years and rising due to the increase in obesity rates in children. Although persistent OSA following adenotonsillectomy is usually associated with obesity and underlying complex disorders, it can also affect otherwise healthy children. Medical treatment strategies are frequently required when adenotonsillectomy is not indicated in children with OSA or if OSA is persistent following adenotonsillectomy. Positive airway pressure treatment is a very effective modality for persistent OSA in childhood; however, adherence rates are low. The aim of this review article is to summarize medical treatment options for OSA in children.
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Project description:This study aimed to investigate the proportion of young OSA adults with sleep-related complaints in a sleep center, affiliated with a tertiary medical center for over a decade. This study presents a chronicle change in the numbers of young adults receiving polysomnography (PSG) and young patients with OSA from 2000 to 2017. We further analyzed 371 young patients with OSA among 2378 patients receiving PSG in our sleep center from 2016 to 2017 to capture their characteristics. Young adults constituted a substantial and relatively steady portion of examinees of PSG (25.1% ± 2.8%) and confirmed OSA cases (19.8 ± 2.4%) even though the total numbers increased with the years. Young adults with OSA tend to be sleepier, have a greater body mass index, and have a higher percentage of cigarette smoking and alcohol consumption. They also complained more about snoring and daytime sleepiness. They had a higher apnea-hypopnea index on average and experienced more hypoxemia during their sleep, both in terms of duration and the extent of desaturation. Even though the prevalence of comorbidities increased with age, hypertension in young male adults carried higher risks for OSA. Young adults with OSA have constituted a relatively constant portion of all confirmed OSA cases across time. The young adults with OSA were heavier, more symptomatic, and with more severe severity.Clinical trial: The Institutional Review Board of Taipei Veterans General Hospital approved the study (VGHIRB No. 2018-10-002CC). The study is registered with ClinicalTrials.gov, number NCT03885440.
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Project description:Rationale: Prior research studies on the association of obstructive sleep apnea (OSA) and pain intensity have examined older patients; there is a need to understand the relationship between OSA and pain intensity among younger adults.Objectives: To examine whether young adults with diagnosed OSA are more likely to report higher pain intensity compared with those without OSA.Methods: We conducted a cross-sectional analysis of a cohort study of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans who had at least one visit to a Veterans Health Administration primary care clinic between 2001 and 2014. OSA was identified using one inpatient or two outpatient International Classification of Diseases, Ninth Revision codes from electronic medical records. Average pain intensity (based on the self-reported 0-10 numeric rating scale over a 12-month period) was categorized as no pain/mild (0-3; no pain) and moderate/severe (4-10; significant pain). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. Multivariate logistic regression models were used, and multiple imputation was performed to generate values for missing variables.Results: We identified 858,226 young adults (mean age 30 yr [SD = 7]), of whom 91,244 (10.6%) had a diagnosis of OSA and 238,587 (27.8%) reported moderate/severe pain for the 12-month average. with young adults without OSA, those with OSA were more likely to report moderate/severe pain intensity (adjusted odds ratio, 1.09; 95% confidence interval, 1.08-1.11) even after controlling for covariates.Conclusions: We found that young adults with OSA have greater odds of comorbid moderate/severe pain. Because of the high prevalence of chronic pain in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity. Future work is needed to determine the role of effective OSA treatment on pain intensity over time in these young adults.
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Project description:BACKGROUND:The known risk factors of childhood OSAS include tonsillar and adenoidhypertrophy, obesity, craniofacial anomalies, neuromuscular disorders and African-American (AA) ancestry. Whether other factors such as allergic rhinitis (AR), premature, environmental tobacco smoking (ETS) are associated with OSAS are inconsistent in different studies. Our study enrolled children of a broad age range and included potential risk factors of OSAS derived from previous studies and our own experience. Our objective is to identify risk factors of OSAS in children in a clinical setting. METHODS:Children between 2 and 15?years of age exhibiting snoring symptoms who visited the sleep center for polysomnography (PSG) were enrolled. All children completed a questionnaire, physical examination and PSG. The questionnaire included demographic data and information related to potential risk factors for sleep disorders. A physical examination included measurements of height, weight, neck circumference, waist and hip ratio, visual evaluation of the tonsils and the degree of adenoid obstruction. Children with obstructive apnea-hypopnea index (OAHI) ? 1 were defined as OSAS. RESULTS:A total of 1578 children were enrolled and1009 children exhibited OSAS. Univariate analyses showed that snoring occurring for ? 3?months, male gender, preterm birth, breastfeeding, obesity, neck circumference???30?cm, waist/hip ratio???0.95, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. The proportion of low educational level was higher in parents who breastfed their babies than those who didn't. Multivariate analysis showed that snoring for ? 3?months, male gender, obesity, breastfeeding, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. Confounders such as socioeconomic status, parental occupation, and health-related behaviors should be explored further to investigate the relationship between breastfeeding and OSAS. CONCLUSION:The independent risk factors for OSAS in children included snoring ? 3?months, male gender, obesity, breastfeeding, tonsillar and adenoid hypertrophy. The study was registered on Clinical Trials government (NCT02447614). The name of the trial is "Follow-up Studies of Primary Snoring (PS) and Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in Chinese Children" and the URL is https://clinicaltrials.gov/.
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