scholarly journals Elevation of CD40/CD40L Inflammatory Pathway Molecules in Carotid Plaques from Moderate-and-Severe Obstructive Sleep Apnea Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 935
Author(s):  
Ewa Migacz ◽  
Wioletta Olejarz ◽  
Alicja Głuszko ◽  
Katarzyna Bednarek-Rajewska ◽  
Robert Proczka ◽  
...  

A chronic inflammatory process characteristic of obstructive sleep apnea promotes vascular endothelial dysfunction and atherogenesis. This process can lead to destabilization and rupture of cardiovascular plaques, which clinically manifests as an acute coronary syndrome or stroke. The aim of this study was to investigate the inflammatory pathway leading to plaque destabilization in non-to-mild and moderate-to-severe groups of OSA patients. This prospective study involved enrollment of patients scheduled for endarterectomy. A sleep study was performed prior to surgery. Immunohistochemistry was performed on atherosclerotic plaques from carotid arteries obtained during standard open endarterectomy to determine levels of CD40, CD40L receptors, MCP-1, and MMP-9. The 46 patients included 14 controls, 13 with mild, 11 with moderate, and 8 with severe OSA. Increased expression of CD40, CD40L receptors, MCP-1, and MMP-9 were found to be proportionate with OSA severity. However, significant differences among groups were observed only for MCP-1 (p = 0.014). Increased expression of inflammatory markers (CD40, CD40L, MCP-1, MMP-9) is associated with increasing OSA severity. This suggests the CD40-CD4-L inflammatory pathway may contribute to plaque instability and rupture in OSA patients.

2020 ◽  
Vol 24 (4) ◽  
pp. 1573-1580 ◽  
Author(s):  
Wioletta Olejarz ◽  
Alicja Głuszko ◽  
Agata Cyran ◽  
Katarzyna Bednarek-Rajewska ◽  
Robert Proczka ◽  
...  

Abstract Background There is growing evidence that obstructive sleep apnea (OSA) promotes vascular endothelial dysfunction and atherogenesis. Pathways that mediate this pathology may include Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) which play a significant role in proinflammatory processes. The aim of this study was to measure the expression of the above-mentioned receptors in relation to OSA severity in carotid plaques obtained during open endarterectomy. Methods This prospective study included patients with a sleep study prior to surgery and a plaque specimen obtained during standard open endarterectomy. Immunohistochemistry of TLR2, TLR4, TLR7, TLR9, RAGE, HMGB1, and NF-κB was performed on atherosclerotic plaques from carotid arteries of patients with and without OSA. Results There were 46 patients (22 women, mean age 73.2 ± 1.3 years): 14 control patients, 13 with mild, 11 with moderate, and 8 with severe OSA. The expression of all TLRs and RAGE increased proportionately with increasing OSA severity. The largest differences between patients with severe OSA and no OSA were found for TLR2 (2.88 ± 0.35 vs. 1.27 ± 0.47, p < 0.001), TLR4 (2.88 ± 0.35 vs. 1.64 ± 0.5, p < 0.001), TLR9 (2.38 ± 0.52 vs. 1.45 ± 0.52, p < 0.01), and RAGE (2.5 ± 0.53 vs. 1.82 ± 0.6, p < 0.05). Conclusion TLR2, TLR4, TLR9, and RAGE expression was significantly increased in carotid plaques of patients with moderate-to-severe OSA when compared with control patients with no OSA and those with mild OSA. TLR and RAGE-mediated pathways may play a significant role in OSA-dependent atherogenesis.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Chieh Yang Koo ◽  

Objective: Obstructive sleep apnea (OSA) is an increasing yet under-recognized risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. Methods: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. In both of these studies, patients presenting with ACS were recruited to undergo an overnight sleep study. OSA was defined as an apnea-hypopnea index (AHI) of ≥15. A bivariate analysis of the factors affecting AHI and an age-adjusted analysis of the effect of BMI on sleep apnea according to ethnicity were conducted. Results: A total of 1961 patients were analyzed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3 kg/m2 for Indians and 25.4 kg/m2 for Chinese to 28.6 kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian patients. Figure 1 shows the forest plot of the prevalence of OSA among the various ethnicities. A significant interaction between BMI and ethnicity to predict OSA was observed. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). Conclusion: There was significant ethnic variation in the prevalence of OSA in patients with ACS, and the magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A166-A166
Author(s):  
Ankita Paul ◽  
Karen Wong ◽  
Anup Das ◽  
Diane Lim ◽  
Miranda Tan

Abstract Introduction Cancer patients are at an increased risk of moderate-to-severe obstructive sleep apnea (OSA). The STOP-Bang score is a commonly used screening questionnaire to assess risk of OSA in the general population. We hypothesize that cancer-relevant features, like radiation therapy (RT), may be used to determine the risk of OSA in cancer patients. Machine learning (ML) with non-parametric regression is applied to increase the prediction accuracy of OSA risk. Methods Ten features namely STOP-Bang score, history of RT to the head/neck/thorax, cancer type, cancer stage, metastasis, hypertension, diabetes, asthma, COPD, and chronic kidney disease were extracted from a database of cancer patients with a sleep study. The ML technique, K-Nearest-Neighbor (KNN), with a range of k values (5 to 20), was chosen because, unlike Logistic Regression (LR), KNN is not presumptive of data distribution and mapping function, and supports non-linear relationships among features. A correlation heatmap was computed to identify features having high correlation with OSA. Principal Component Analysis (PCA) was performed on the correlated features and then KNN was applied on the components to predict the risk of OSA. Receiver Operating Characteristic (ROC) - Area Under Curve (AUC) and Precision-Recall curves were computed to compare and validate performance for different test sets and majority class scenarios. Results In our cohort of 174 cancer patients, the accuracy in determining OSA among cancer patients using STOP-Bang score was 82.3% (LR) and 90.69% (KNN) but reduced to 89.9% in KNN using all 10 features mentioned above. PCA + KNN application using STOP-Bang score and RT as features, increased prediction accuracy to 94.1%. We validated our ML approach using a separate cohort of 20 cancer patients; the accuracies in OSA prediction were 85.57% (LR), 91.1% (KNN), and 92.8% (PCA + KNN). Conclusion STOP-Bang score and history of RT can be useful to predict risk of OSA in cancer patients with the PCA + KNN approach. This ML technique can refine screening tools to improve prediction accuracy of OSA in cancer patients. Larger studies investigating additional features using ML may improve OSA screening accuracy in various populations Support (if any):


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Eileen R. Chasens ◽  
Susan M. Sereika ◽  
Martin P. Houze ◽  
Patrick J. Strollo

Objective.This study examined the association between obstructive sleep apnea (OSA), daytime sleepiness, functional activity, and objective physical activity.Setting.Subjects (N=37) being evaluated for OSA were recruited from a sleep clinic.Participants. The sample was balanced by gender (53% male), middle-aged, primarily White, and overweight or obese with a mean BMI of 33.98 (SD=7.35;median BMI=32.30). Over 40% reported subjective sleepiness (Epworth Sleepiness Scale (ESS) ≥10) and had OSA (78% with apnea + hypopnea index (AHI) ≥5/hr).Measurements.Evaluation included questionnaires to evaluate subjective sleepiness (Epworth Sleepiness Scale (ESS)) and functional outcomes (Functional Outcomes of Sleep Questionnaire (FOSQ)), an activity monitor, and an overnight sleep study to determine OSA severity.Results.Increased subjective sleepiness was significantly associated with lower scores on the FOSQ but not with average number of steps walked per day. A multiple regression analysis showed that higher AHI values were significantly associated with lower average number of steps walked per day after controlling patient's age, sex, and ESS.Conclusion.Subjective sleepiness was associated with perceived difficulty in activity but not with objectively measured activity. However, OSA severity was associated with decreased objective physical activity in aging adults.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Jason Ng ◽  
Phyllis C Zee ◽  
Jeffrey J Goldberger ◽  
Kristen L Knutson ◽  
Kiang Liu ◽  
...  

Introduction Sleep duration is significantly associated with cardiovascular disease risk factors such as hypertension, diabetes, and obesity in adults at low risk for obstructive sleep apnea. Although it is known that apnea increases the risk for sudden cardiac death, it is not known whether adults with short sleep duration independent of apnea have a higher risk for cardiac arrhythmias Hypothesis We tested the hypothesis that sleep duration in adults at low risk for obstructive sleep apnea would be associated with ECG measures that are known risk factors for ventricular arrhythmias. Methods The Chicago Area Sleep Study recruited 610 participants via commercially available telephone listings. Participants were screened using in-home apnea detection equipment (ApneaLinkTM) for one night to exclude subjects with apnea/hypopnea index ≥ 15. Participants wore wrist actigraphs for 7 days to objectively determine sleep duration. A 10-minute 12-lead ECG was recorded for each subject. Standard measures of heart rate, PR interval, and QTc interval were obtained along with markers of ventricular repolarization, Tpeak to Tend interval (Tpe) and spatial QRS-T angle. Signal-averaged ECG analysis was performed to measure filtered QRS duration (fQRSd), RMS voltage of terminal 40 ms (RMS), and duration of terminal QRS signals <40μV (LAS). Participants with atrial fibrillation, >20% ectopic beats and those using antihypertensive and sleep medications were excluded from analysis. The effect of sleep duration on the ECG parameters was estimated using a multiple linear regression model adjusting for demographics (sex, age, and race) and cardiovascular risk factors (BMI, hypertension, coronary heart disease, and diabetes). Results ECGs from a total of 504 participants (200 male, 48±8 years old) were analyzed. Mean sleep duration was 7±1 hrs, heart rate was 64±9 bpm, PR interval was 165±18 ms, and QTc interval was 424±23 ms. Mean Tpe interval was 83±14 ms and spatial QRS-T angle was 29±26 deg. The signal-averaged ECG measures of fQRSd, RMS, and LAS had mean values of 78±12 ms, 58±34 μV, and 24±9 ms, respectively. In an unadjusted model, there was a borderline association between sleep duration and QTc (β=0.004 ms/hr, SE=0.0023, p=0.08). However, that association was no longer significant following adjustment with demographics and cardiovascular risk factors. No other ECG measures were associated with sleep duration. Conclusions In a population at low risk of obstructive sleep apnea, ECG-based measures of cardiovascular risks were not associated with sleep duration. Previously reported associations between short sleep and cardiovascular events may not be arrhythmic in origin.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel Combs ◽  
Vanessa Fernandez ◽  
brent j barber ◽  
Wayne J Morgan ◽  
Chiu-Hsieh Hsu ◽  
...  

Introduction: Obstructive sleep apnea (OSA) is associated with cardiac dysfunction in children without congenital heart disease (CHD). Children with CHD are at increased risk for OSA and may be susceptible to further cardiovascular consequences due to OSA but the extent and nature of such cardiovascular effects of OSA are unknown. Methods: Children (6-17 years old) with corrected CHD without current cyanosis or Down syndrome were recruited from pediatric cardiology clinic. Home sleep tests were done to determine the presence and severity of OSA. OSA was defined as an obstructive apnea hypopnea index (oAHI) ≥1. Mild OSA was defined as an oAHI of ≥1 to <5 and moderate OSA was defined as an oAHI of ≥5 to <10. Standard clinically indicated echocardiograms were performed in clinic. Echocardiographic findings were compared between children with CHD with and without comorbid OSA using t-tests, Wilcoxon-sign rank tests as well as linear or logistic regression as appropriate. Results: Thirty-two children had sleep study and echocardiographic data available. OSA was present in 18 children (56%). OSA was mild in 89% and moderate in 11% of cases. There were no significant differences in age, body mass index, CHD severity, gender or ethnicity between children with and without OSA. Children with OSA had larger height-indexed right ventricular end-diastolic diameter (RVDi) compared to those without OSA (median 1.35, 95% CI 1.09, 1.56 vs. 1.21, 95% CI 1.01, 1.57; p=0.04). Children with moderate OSA had a reduced left ventricular shortening fraction compared to both those with mild OSA and no OSA (30.0 ± 6.1% vs. 38.7 ± 4.4%; p=0.009 and 39.2 ± 3.6%; p=0.007, respectively). Children with moderate OSA had increased left ventricular end-systolic diameter compared to those with mild OSA and no OSA (3.4 ± 0.4 cm vs. 2.5 ± 0.4; p=0.007 and 2.4 ± 0.5; p=0.001, respectively). Children with an RVDi above the median were seven times more likely to have OSA than those with an RVDi below the median (odds ratio 6.9.; 95% CI 1.3, 35; p=0.02). Conclusions: OSA is associated with changes in cardiac morphology and reduced contractility in children with CHD. Additionally, the presence of right ventricular dilation may suggest the need for OSA evaluation in children with CHD.


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