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Study Objectives: We investigated the associations between multiple sleep dimensions in obstructive sleep apnea (OSA) and carotid intima-media thickness (CIMT), an early sign of atherosclerosis, in participants from the Shanghai Sleep Health Study., Methods: We performed secondary analysis of SSHS in a group of subjects who underwent ultrasound evaluation from 2018 to 2022. Multiple sleep dimensions were measured using standard polysomnography. CIMT was measured from ultrasound images as an early sign of atherosclerosis. Multivariable-adjusted linear regression and logistic regression analyses were performed to detect associations between sleep traits in OSA and CIMT., Results: CIMT was found to increase with increasing severity of OSA ( P < .001). When adjusted for conventional risk factors, microarousal index and hypoxic burden were positively correlated with CIMT, while slow-wave sleep and mean apnea-hypopnea event duration showed a negative correlation with CIMT (all P < .01). In binary logistic regression analysis, participants with a high microarousal index, less slow-wave sleep, higher hypoxic burden, and shorter mean apnea-hypopnea event duration showed a higher prevalence of thick CIMT with no evidence of interaction by age, sex, or body mass index ( P -interaction > .05)., Conclusions: Patients with more severe sleep fragmentation, more severe hypoxemia, and increased arousability were more likely to have increased CIMT after adjusting for potential confounders. It is important to evaluate novel indices of sleep fragmentation, hypoxemia, and arousability in OSA for early detection and prevention of cardiovascular disease, including stroke., Clinical Trial Registration: Registry: Chinese Clinical Trial Registry; Name: Establishing Bio-bank and Cohort of OSAHS in Hospital-based Population; URL: http://www.chictr.org.cn/showproj.aspx?proj=43057; Identifier: ChiCTR1900025714., Citation: Huang W, Zhou E, Zhang J, et al. Association between multiple sleep dimensions in obstructive sleep apnea and an early sign of atherosclerosis. J Clin Sleep Med . 2024;20(7):1093-1104., (© 2024 American Academy of Sleep Medicine.)

Background: Positional OSA (POSA) is a recognized subtype of OSA that exhibits distinct endotypic characteristics when compared with nonpositional OSA (NPOSA). The basis for the disparity in endotypes between these subtypes remains poorly understood., Research Question: (1) Do individuals with NPOSA and POSA have different underlying OSA endotypes? (2) Which endotypic characteristics are critical in determining NPOSA and POSA severity?, Study Design and Methods: Within the Shanghai Sleep Health Study cohort, individuals with OSA were recruited and classified as having POSA or NPOSA. Endotypes were calculated using polysomnography., Results: Endotype analysis was conducted in 1,036 individuals with OSA. Compared with individuals with NPOSA, those with POSA had lower loop gain calculated during all sleep stages and all sleep positions (0.55; interquartile range [IQR], 0.46-0.66 vs 0.68, IQR, 0.52-0.90; P < .001), lower arousal threshold calculated during all sleep stages and all sleep positions (ArTH All ) (138.67; IQR, 118.94-180.87 percentage of the eupneic ventilation [%Veupnea] vs 189.00; IQR, 129.71-257.76 %Veupnea; P < .001), lower pharyngeal collapsibility calculated during all sleep stages and all sleep positions (Vpassive All ) (91.85; IQR, 83.13-95.15 %Veupnea vs 76.38; IQR, 23.77-92.08 %Veupnea; P < .001), and higher muscle compensation calculated during all sleep stages and all sleep positions (6.50; IQR, -6.77 to 16.39 %Veupnea vs 3.65; IQR, -10.47 to 12.14 %Veupnea; P = .003). Logistic regression analyses indicated that higher Vpassive All was associated with increased odds of POSA vs NPOSA. In NPOSA, fully adjusted linear regression analyses indicated that Vpassive All (β = -0.55; 95% CI, -0.68 to -0.42; P < .001) and lower loop gain calculated during all sleep stages and all sleep positions (β = 0.19; 95% CI, 0.08-0.30; P < .001) were significant independent predictors of the apnea hypopnea index, with Vpassive All being the most critical factor. In contrast, in POSA, collapsibility appeared to be less influential (β = -0.09; 95% CI, -0.21 to 0.03; P = .138). Nonanatomic endotypic characteristics (LG All : β = 0.29; 95% CI, 0.18-0.41; P < .001; arousal threshold in all sleep stages and all sleep positions: β = 0.15; 95% CI, 0.01-0.28; P = .031; muscle compensation in all sleep stages and all sleep positions: β = -0.21; 95% CI, -0.29 to -0.12; P < .001) were significant in determining the severity of POSA, with loop gain being the most crucial factor., Interpretation: This study highlights the differences in endotypes between NPOSA and POSA. In Chinese individuals, anatomic factors were more significant in determining the severity of NPOSA, whereas nonanatomic traits were more likely to determine the severity of POSA. Future research should focus on developing personalized management strategies for individuals with NPOSA and POSA based on their endotypes., Trial Registration: Chinese Clinical Trial Registry; No.: ChiCTR1900025714; URL: https://www.chictr.org.cn/indexEN.html., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation., Methods: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients., Results: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 ( r  = -0.19, p  < .05) and LPS ( r  = -0.20, p  < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 ( r  = -0.46, p  < .01), LPS ( r  = -0.35, p  < .01) and CPR ( r  = -0.30, p  < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients., Conclusions: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients.

Objectives: Obstructive sleep apnea hypopnea syndrome (OSA) is an independent risk factor for neurocognitive and behavioral problems and cardiovascular and metabolic morbidities, ultimately increasing mortality. However, OSA diagnosis is time-consuming, labor-intensive, and expensive. We evaluated the predictive utility of the sleep apnea-specific hypoxic burden (SASHB) in terms of OSA and the severity thereof in Han Chinese individuals., Methods: From January 2019 to July 2022, subjects with suspected OSA were recruited in the sleep center of the Shanghai Sixth People's Hospital during sleep evaluation via standard polysomnography. Basic anthropometric measurements and polysomnographic indicators were collected; SASHB was calculated based on the SpO 2 trends of apnea or hypopnea events. Models predictive of OSA were established via logistic regression in the experimental group and verified in an independent group by drawing receiver operating characteristic (ROC) curves., Results: A total of 2303 subjects with suspected OSA (1200 in the experimental group and 1103 in the validation group) were included. SASHB was positively correlated with the apnea-hyponea index (AHI) in all subjects (r = 0.823, P < 0.001). SASHB distinguished OSA from non-OSA subjects in both the experimental group {area under the curve (AUC) 0.948 [0.934∼0.962]} and the validation group (AUC 0.931 [0.913∼0.949]). SASHB predicted OSA severity well, better than did the neck, waist, or hip circumference; the lowest or mean oxygen saturation; and the Epworth sleepiness scale score., Conclusion: SASHB predicted OSA both accurately and efficiently in a Chinese Han population. Further studies are warranted to verify our findings in community samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

In our large-scale study, the correlation between obstructive sleep apnea (OSA) related to rapid eye movement (REM) sleep and cardiac autonomic dysfunction was assessed by standard polysomnography (PSG). Cardiac autonomic dysfunction was evaluated by the measurement of heart rate variability (HRV). The cardiovascular disease (CVD) risk was determined using the cross-sectional prevalence of CVD and its overall 10 year risk according to the Framingham risk score (FRS). 4152 individuals were included in the study. A higher apnea-hypopnea index during REM sleep (AHI REM ) was correlated with increased CVD risk. The adjusted odds ratios (95% CIs) for CVD prevalence and its high 10 year risk in participants having severe OSA during REM sleep (AHI REM  ≥30 events/h) were 1.452 (1.012-2.084) and 1.904 (1.470-2.466) in the demographic adjusted model and 1.175 (0.810-1.704) and 1.716 (1.213-2.427) in the multivariate adjusted model, respectively, compared with the group with a AHI REM of <5 events/h. Fully adjusted multivariate linear regression models showed the independent association between AHI REM and a more elevated ratio of low-frequency and high-frequency (LF/HF) and LF in normalised units [LF (n.u.)] (P = 0.042, P = 0.027 in all participants and P = 0.033, P = 0.029 in participants with AHI during non-REM sleep <5 events/h, respectively). Mediation analysis demonstrated that OSA during REM sleep and CVD risk was significantly mediated by LF/HF and LF (n.u.). OSA during REM sleep may be a marker behind CVD risk because it promotes cardiac autonomic dysfunction., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Objective: Autonomic dysfunction is an independent risk factor for cardiovascular disease (CVD). Both obesity and obstructive sleep apnea (OSA) are associated with heart rate variability (HRV) (a hall marker of sympathetic arousal) and increased risk of CVD. This study aims to investigate whether anthropometric parameters could predict reduced HRV in adult OSA during wakefulness., Study Design: Cross-sectional study., Setting: Sleep center of Shanghai Jiao Tong University Affiliated Sixth Hospital from 2012 to 2017., Methods: Total of 2134 subjects (503 non-OSA and 1631 OSA) were included. Anthropometric parameters were recorded. HRV was recorded during a 5-minute wakefulness period and analyzed by using time-domain method and frequency-domain method. Multiple step-wise linear regressions were performed to determine significant predictors of HRV with and without adjustments. Multiplicative interactions between gender, OSA, and obesity on HRV were also determined and evaluated., Results: Waist circumference (WC) was significant negative determinant of root mean square of successive NN intervals (β = -.116, p < .001) and high-frequency power (β = -.155, p < .001). Age was the strongest determining factor of HRV. Significant multiplicative interactions between obesity and OSA on HRV, gender, and obesity on cardiovascular parameters were observed., Conclusion: Anthropometric parameters could predict reduced HRV during wakefulness in patients with OSA, especially WC was the strongest influenceable factor. Obesity and OSA had significant multiplicative interaction on HRV. Gender and obesity had significant multiplicative interaction on cardiovascular parameters. Early intervention for obesity, especially centripetal obesity, may improve reduction of autonomic function and risk of CVD., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objectives: We explored whether a new combination of eye mask sleep position therapy (SPT) and oral appliance therapy (OAT) was more effective at treating positional obstructive sleep apnea (POSA) than was the use of either device alone., Methods: In this randomized controlled trial, 60 POSA subjects diagnosed by standard polysomnography (PSG) were divided into three groups (ratio 1:1:1): SPT, OAT, and SPT combined with OAT (SOT). Participants underwent hospital-based follow-ups during months 1 and 6 after beginning treatment. The primary outcome was the decline in the apnea hypopnea index (AHI) at month 6. The secondary outcomes were changes in oxygen-derived parameters and the curative effect at month 6., Results: After 6 months of treatment, PSG showed that SPT, OAT, and SOT all improved the AHI and oxygen-derived parameters. The AHI decline was significantly better in the SOT group than in the OAT or SPT group (71.58% [50.56-84.84%] for SOT, 44.42% [21.23-67.52%] for OAT, and 33.24% [19.03-54.62%] for SPT at 6 months) (P = 0.018 and P < 0.001 for the comparisons of SOT with OAT and SOT with SPT, respectively). In terms of oxygen-derived parameters, only the sleep apnea-specific hypoxic burden (SASHB) improved more in the SOT group (76.89% [57.43-85.91%]) than in the other groups (44.73% [32.38-72.69%] for OAT and 41.82% [15.40-65.24%] for SPT, P = 0.002 and P < 0.001 for the comparisons of SOT with OAT and SOT with SPT, respectively). The efficacies of SPT, OAT, and SOT were 36.84%, 50%, and 80% at 6 months; the SOT group evidenced the highest value (rate ratio [95% confidence interval] 1.78 (1.05-3.03), P = 0.048 and 2.17 (1.16-4.07), P = 0.010, for the comparisons of SOT with OAT and SOT with SPT, respectively)., Conclusion: The combination of SPT and OAT was better than either treatment alone and may represent a good option for the treatment of POSA., Trial Registration: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn/showproj.aspx?proj=42,852; No. ChiCTR1900025584., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the prevalence, characteristics, and respiratory arousal threshold (ArTH) of Chinese patients with positional obstructive sleep apnea (POSA) according to the Cartwright Classification (CC) and Amsterdam Positional Obstructive Sleep Apnea Classification (APOC)., Methods: A large-scale cross-sectional study was conducted in our sleep center from 2007 to 2018 to analyze the clinical and polysomnography (PSG) data of Chinese POSA patients. Low ArTH was defined based on PSG indices., Results: Of 5,748 OSA patients, 36.80% met the CC criteria, and 42.88% the APOC criteria, for POSA. The prevalence of POSA was significantly higher in women than men (40.21% and 46.52% vs. 36.13% and 42.18% for CC and APOC, respectively). Chinese POSA patients had a lower apnea hypopnea index (AHI) and lower oxygen desaturation index, shorter duration of oxygen saturation (SaO 2 ) < 90%, and a higher mean SaO 2 and higher lowest SaO 2 value compared to subjects with non-positional OSA (NPOSA). More than 40% of the POSA patients had a low ArTH; the proportion was extremely high in the supine-isolated-POSA (si-POSA) group and APOC I group. In multivariate logistic regression analyses, higher mean SaO 2 and lower AHI during sleep were positive predictors of POSA., Conclusions: According to the CC and APOC criteria, more than 1/3 of our Chinese subjects with OSA had POSA. Chinese POSA patients had less severe OSA and nocturnal hypoxia. Compared to NPOSA patients, significantly more patients with POSA had a low ArTH. A low ArTH may be an important endotype in the pathogenesis of POSA, especially in patients with si-POSA and APOC I. Further studies are necessary to develop personalized management strategies for POSA patients., Trial Registration: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn ; No. ChiCTR1900025714 (retrospectively registered)., (© 2022. The Author(s).)

Objective: Roux-en-Y gastric bypass (RYGB) surgery is an effective type of weight loss management and may improve obesity-related obstructive sleep apnea (OSA). Obese subjects who meet the criteria for surgery with OSA were enrolled. We investigated the metabolomic effects of RYGB on OSA., Methods: Clinical data, serum measurements including indices of glycolipid metabolism, and polysomnography (PSG) measurements were collected at baseline and 6 months after RYGB surgery. Metabolomic analysis was performed using ultra-performance liquid chromatography-mass spectrometry., Results: A group of 37 patients with obesity, type 2 diabetes (T2DM) and suspected OSA were enrolled of which 27 were OSA subjects. After RYGB surgery, metabolic outcomes and sleep parameters were all significantly improved. The OSA remission group had lower valine, isoleucine, and C24:1(cis-15) levels, and higher trimethylamine N-oxide, hippurate, and indole-3-propionic acid levels after RYGB surgery. A combination of preoperative indices (age, apnea-hypopnea index (AHI), fasting C-peptide level, and hippurate level) predicted the RYGB effect size in obese patients with T2DM and OSA, with an area under receiver operating characteristic curve of 0.947, specificity of 82.4%, and sensitivity of 100%., Conclusions: RYGB surgery may significantly improve the metabolic status of patients with obesity, T2DM and OSA. A combination of preoperative indices (age, AHI, fasting C peptide level, and hippurate level) may be useful for predicting the effect size of RYGB in obese patients with T2DM and OSA. The mechanisms underlying OSA remission need to be explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Zhong, Xu, Xu, Wang, Wang, Li, Liu, Zou, Zhu, Zheng, Yi, Guan and Yin.)

Purpose: To evaluate whether a predictive model based on nocturnal minimal oxygen saturation (SpO 2 ) alone can accurately detect the presence of obstructive sleep apnea (OSA) in a population with suspected OSA., Methods: A total of 4297 participants with suspected OSA were enrolled in this study, and laboratory-based polysomnography (PSG) tests were performed at sea level in all subjects. Nocturnal minimal SpO 2 was obtained automatically as part of the PSG test. Stratified sampling was used to divide the participants' data into the training set (75%) and the test set (25%). An OSA detection model based on minimal SpO 2 alone was created using the training set data and its performance was evaluated using the independent test set data ("hold-out" evaluation). Gender-specific models, and models based on minimal SpO 2 in combination with other predictive factors (age, body mass index, waist-to-hip ratio, snoring grade, Epworth Sleepiness Scale score, and comorbidities), were also created and compared in terms of OSA detection performance., Results: The prevalence of OSA was 85.6% in our study population. The models including multiple predictors, and the gender-specific models, failed to outperform the model based solely on minimal SpO 2 , which showed good predictive performance (C statistic, 0.922) having an overall accuracy rate of 0.86, sensitivity of 0.87, specificity of 0.84, positive predictive value of 0.97, and positive likelihood ratio of 5.34. In addition, the model based on minimal SpO 2 alone could also accurately predict the presence of moderate-to-severe OSA and severe OSA, with C statistics of 0.914 and 0.900, respectively., Conclusions: A predictive model based on nocturnal minimal SpO 2 alone may be an alternative option to detect the presence of OSA in a high-risk population when standard diagnostic tests are unavailable.

Obesity is strongly correlated with obstructive sleep apnea (OSA), and bariatric surgery can effectively treat obesity and alleviate OSA. However, the contributing factors are still unclear. We aimed to explore the relationship between betatrophin and OSA in patients undergoing Roux-en-Y gastric bypass (RYGB) surgery. Our study consisted of thirty-seven individuals with OSA and type 2 diabetes (16 males, 21 females) undergoing RYGB surgery. The polysomnography test, anthropometric results, serum betatrophin, and abdominal magnetic resonance images were evaluated both before and 1 year after RYGB surgery. Factors that may correlate with the alleviation of OSA were investigated. In our study, RYGB surgery significantly decreased apnea hypopnea index (AHI) and serum betatrophin concentration (p < 0.001). The abdominal visceral fat area, subcutaneous fat area and HOMA-IR were also significantly decreased (p < 0.001). The preoperative AHI, postoperative AHI and the change in AHI were significantly correlated with the preoperative betatrophin, postoperative betatrophin and the change in betatrophin, respectively (p < 0.05). These correlations were still significant after adjustment for other risk factors. The change in betatrophin was also independently associated with the change in minimum oxygen saturation (p < 0.001). Our data might indicate that serum betatrophin was significantly independently correlated with the improvement of OSA after bariatric surgery.

Obesity is strongly correlated with the pathogenesis of obstructive sleep apnea (OSA); myokines may play important roles in this condition. We performed a body mass index- (BMI) and physical activity- (PA) matched study to explore the relationship between the irisin level and OSA. Ninety-six consecutive participants were recruited. After matching in terms of BMI and PA, 28 OSA patients and 28 healthy controls were finally included. Whole-night laboratory-based polysomnography was used to identify OSA. The Recent Physical Activity Questionnaire and Epworth Sleepiness Scale Questionnaire were employed to assess PA over the past 4 weeks, and daytime sleepiness. We measured serum irisin, fasting blood glucose, and insulin levels in blood samples. The serum irisin concentrations differed significantly between the control, mild OSA, moderate OSA, and severe OSA groups (p < 0.001) and correlated significantly with the apnea/hypopnea index (AHI) (r = -0.787, p < 0.001). All of age, BMI, neck, waist and hip circumferences, fasting blood glucose level, and the Epworth Sleepiness Scale and PA scores were associated with irisin levels (p < 0.05). After adjustment for these factors, the serum irisin level was independently correlated with the AHI (r = -0.428, p = 0.002). On forward logistic regression analysis, the association remained significant in the final multiple regression model (β = -0.107, p < 0.001). The serum irisin concentration was significantly correlated with OSA severity, independently of BMI and PA. Further studies are needed to determine the molecular mechanisms in play.