Obstructive sleep apnea: an emerging risk factor for atherosclerosis.
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ABSTRACT:
SUBMITTER: Drager LF
PROVIDER: S-EPMC3198492 | biostudies-other | 2011 Aug
REPOSITORIES: biostudies-other
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Project description:Common risk factors for obstructive sleep apnea (OSA) and Barrett's esophagus (BE) include obesity and gastroesophageal reflux disease (GERD). The aims of this study were to assess the association between OSA and BE and to determine whether the association is independent of GERD and body mass index (BMI).Patients who had undergone a diagnostic polysomnogram and esophagogastroduodenoscopy were identified by using Mayo Clinic (Rochester, Minnesota) databases from January 2000-November 2011. They were randomly matched for age, sex, and BMI at time of polysomnogram into the following groups: BE but no OSA (n = 36), OSA but no BE (n = 78), both (n = 74), or neither (n = 74). Clinical and demographic variables were abstracted from medical records. The association between OSA and BE was assessed by using a multiple variable logistic model that incorporated age, sex, BMI, clinical diagnosis of GERD, and smoking history.Subjects with OSA had an 80% increased risk for BE compared with subjects without OSA (odds ratio, 1.8; 95% confidence interval, 1.1-3.2; P = .03). These findings were independent of age, sex, BMI, GERD, and smoking history. Increasing severity of OSA, measured by using the apnea-hypopnea index, was associated with an increased risk of BE (odds ratio, 1.2 per 10-unit increase in apnea-hypopnea index; 95% confidence interval, 1.0-1.3; P = .03).In this case-control study, OSA was associated with an increased risk of BE, potentially through BMI and GERD independent mechanisms. Patients with OSA may benefit from evaluation for BE.
| S-EPMC3952037 | biostudies-literature
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:BackgroundObstructive sleep apnea may be associated with development of CKD through hypoxia, inflammation, and oxidative stress. Individuals with this sleep disorder are also at increased risk for established CKD risk factors, including obesity, hypertension, and type 2 diabetes.MethodsWe examined the association between obstructive sleep apnea, other sleep characteristics, and risk of incident CKD (stage 3 or higher) in 1525 participants (mean age, 62.5 years; 52.4% women) in the Atherosclerosis Risk in Communities (ARIC) study who completed in-home polysomnography assessments. We used the apnea-hypopnea index (events per hour) to define obstructive sleep apnea severity (normal, <5.0; mild, 5.0-14.9; moderate, 15.0-29.9; and severe, ≥30.0) and defined incident CKD (stage 3 or higher) as eGFR<60 ml/min per 1.73 m2 and ≥25% decline from baseline, CKD-related hospitalization or death, or ESKD. Cox proportional hazards regression was used to estimate obstructive sleep apnea severity with risk of incident CKD, adjusting for demographics, lifestyle behaviors, and cardiometabolic conditions.ResultsDuring 19 years (median) of follow-up, 461 CKD events occurred. After adjustment for demographics and lifestyle behaviors, severe obstructive sleep apnea associated with increased risk of CKD (hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.08 to 2.10), which was attenuated after adjustment for body mass index (HR, 1.07; 95% CI, 0.75 to 1.52). No other sleep characteristics associated with incident CKD.ConclusionsWe found a link between obstructive sleep apnea and an elevated risk of stage 3 CKD or higher, but this association was no longer significant after adjusting for obesity, a risk factor for both conditions. Given the high prevalence of obstructive sleep apnea and CKD among adults, further investigation is warranted.
| S-EPMC7460900 | biostudies-literature
Project description:Leukotriene B(4) (LTB(4)) production increases in obstructive sleep apnea syndrome (OSA) and is linked to early vascular remodeling, the mechanism of which is unknown. The objective of this study was to to determine the molecular mechanisms of LTB(4) pathway activation in polymorphonuclear cells (PMNs) and early vascular remodeling in OSA and the specific contribution of intermittent hypoxia (IH). PMNs were isolated from 120 OSA patients and 33 healthy subjects and used for measurements of LTB(4) production, determination of mRNA and protein expression levels, or exposed for four cycles of in vitro IH. PMNs derived from OSA patients exhibited increased LTB(4) production, for which apnea-hypopnea index was an independent predictor (P=0.042). 5-Lipoxygenase-activating protein (FLAP) mRNA and protein increased significantly in PMNs from OSA patients versus controls and were associated with carotid luminal diameter and intima-media thickness. LTB(4) (10 ng/ml) increased IL-6 (P=0.006) and MCP-1 (P=0.002) production in OSA patient monocytes. In vitro exposure of PMNs from controls to IH enhanced FLAP mRNA levels (P= 0.027) and induced a 2.7-fold increase (P=0.028) in LTB(4) secretion compared with PMNs exposed to normoxia. In conclusion, upregulation of FLAP in PMNs in response to IH may participate in early vascular remodeling in OSA patients, suggesting FLAP as a potential therapeutic target for the cardiovascular morbidity associated with OSA.
| S-EPMC3413233 | biostudies-literature
Project description:Study objectivesProspective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns.MethodsARIC participants (n = 966; mean age 61 y, 55% women) with in-home polysomnography (1996-1998) and repeated cognitive testing were followed for 15 y. Three cognitive tests (Delayed Word Recall, Word Fluency, and Digit Symbol Substitution) were administered at two time points (1996-1998 and 2011-2013). Ten additional cognitive tests were administered at the 2011-2013 neurocognitive examination. OSA was modeled using established clinical OSA severity categories. Multivariable linear regression was used to explore associations of OSA and other sleep indices with change in cognitive tests between the two assessments.ResultsA median of 14.9 y (max: 17.3) passed between the two cognitive assessments. OSA category and additional indices of sleep (other measures of hypoxemia and disordered breathing, sleep fragmentation, sleep duration) were not associated with change in any cognitive test. Analyses of OSA severity categories and 10 cognitive tests administered only in 2011-2013 also showed little evidence of an association.ConclusionsOverall, abnormal sleep quality and quantity at midlife was not related to cognitive decline and later-life cognition. The effect of adverse sleep quality and quantity on cognitive decline among the elderly remains to be determined.
| S-EPMC4712410 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interfering intermediates mechanisms associated with cardiovascular complications. We have thus initiated the Epigenetics modification in Obstructive Sleep Apnea (EPIOSA) study (ClinicalTrials.gov identifier: NCT02131610).EPIOSA is a prospective cohort study aiming to recruit 350 participants of caucasian ethnicity and free of other chronic or inflammatory diseases: 300 patients with prevalent OSA and 50 non-OSA subjects. All of them will be follow-up for at least 5 years. Recruitment and study visits are performed in single University-based sleep clinic using standard operating procedures. At baseline and at each one year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized questionnaire and physical examination to determine incident comorbidities and health resources utilization, with a primary focus on cardiovascular events. Confirmatory outcomes information is requested from patient records and the regional Department of Health Services. Every year, OSA status will be assessed by full sleep study and blood samples will be obtained for immediate standard biochemistry, hematology, inflammatory cytokines and cytometry analysis. For biobanking, aliquots of serum, plasma, urine, mRNA and DNA are also obtained. Bilateral carotid echography will be performed to assess subclinical atherosclerosis and atherosclerosis progression. OSA patients are treated according with national guidelines.EPIOSA will enable the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of treated and non-treated patients with OSA compared with non OSA subjects.
| S-EPMC4107483 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is common and is associated with a number of adverse outcomes, including an increased risk for cardiovascular disease. Typical treatment approaches, including positive airway pressure, oral appliances, various upper airway surgeries, and/or weight loss, can improve symptoms and reduce the severity of disease in select patient groups. However, these approaches have several potential limitations, including suboptimal adherence, lack of suitability for all patient groups, and/or absence of adequate outcomes data. Emerging potential therapeutic options, including nasal expiratory positive airway pressure (PAP), oral negative pressure, upper airway muscle stimulation, and bariatric surgery, as well as improvements in existing treatments and the utilization of improving technologies are moving the field forward and should offer effective therapies to a wider group of patients with OSA.
| S-EPMC4017906 | biostudies-literature
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/.
| S-EPMC7057627 | biostudies-literature
Project description:Obstructive sleep apnoea (OSA) has been linked to cardiovascular risk factors, such as hypertension, and clinical cardiovascular endpoints. Our aim was to assess whether OSA is independently associated with atherosclerosis and vascular dysfunction as assessed by cardiovascular magnetic resonance (CMR).58 patients with OSA and 39 matched control subjects without OSA underwent CMR of the aorta and carotid arteries. Carotid and aortic wall thickness and aortic distensibility were measured. Multi-weighted, high resolution CMR imaging was used for carotid atheroma characterization according to the American Heart Association (AHA) atheroma classification, modified for CMR.Carotid [1.47±0.03 mm vs. 1.26±0.05 mm, (P<0.01)] and aortic wall thickness [2.95±0.09 mm vs. 2.05±0.07 mm, (P<0.001)] were increased in patients with OSA compared to controls. Aortic distensibility was decreased in patients with OSA [3.62±0.3 vs. 4.75±0.2 mmHg(-1)×10(-3), (P<0.05)]. Prevalence of carotid plaque, average carotid atheroma class, and prevalence of high risk features of carotid atheroma were increased in patients with OSA (P<0.005 for all). On multivariate analysis, Oxygen desaturation index (ODI) emerged as an independent predictor of carotid and aortic wall thickness, but not of aortic stiffness.OSA is associated with increased carotid and aortic atheroma burden and with advanced, high risk carotid atherosclerotic plaques, but not with aortic stiffening.
| S-EPMC4978311 | biostudies-literature