Hypoxic Burden Research Articles

Combination Drug Therapy with Acetazolamide, Eszopiclone +/- Venlafaxine for Obstructive Sleep Apnea (RESCUE-Combo): A Randomized, Double-blind, Placebo-controlled Trial.

Acetazolamide, eszopiclone, and venlafaxine may target different underlying mechanisms of obstructive sleep apnea (OSA) and individually may partially improve OSA severity in select patients. We tested whether acetazolamide+eszopiclone (DualRx) improves OSA severity. We further explored whether addition of venlafaxine (TripleRx) improves OSA in patients who do not fully respond to DualRx. In this double-blind, crossover trial, twenty OSA patients underwent a baseline polysomnography followed by DualRx/Placebo phases in random order. Subsequently, 18 patients underwent an open-label TripleRx phase. Each phase lasted 3 days and concluded with polysomnography. The primary outcome was the placebo-adjusted change in apnea-hypopnea index during supine, non-rapid eye movement sleep (AHINREM,supine) from baseline to DualRx. Secondary outcomes included other OSA metrics, sleep parameters, and select clinical outcomes (blood pressure, symptoms, vigilance). Participants were on average middle-aged, overweight and relatively diverse (20% women, 60% non-white) with severe OSA (median [IQR] AHINREM,supine 32.8 [20-48.8] events/h). Compared with placebo, DualRx was well tolerated, improved the AHINREM,supine (-13.8 [-24.1 to -5.2] events/h or -45 [-77 to -14] %, PWilcoxon=0.003), AHIOverall, hypoxic burden and sleep architecture (P<0.05), but not the selected clinical outcomes. TripleRx did not provide a clear benefit relative to DualRx, although some measures of OSA-related hypoxemia improved more substantially. There were no serious side effects. Short-term use of dual-drug therapy with acetazolamide+eszopiclone substantially improved OSA severity. Adding venlafaxine did not generally improve OSA severity but may be beneficial for some patients. Longer term studies are needed to assess effects on clinically important outcomes. Clinical trial registration available at www. gov, ID: NCT04639193.

Obstructive sleep apnoea and lung function, and their association with nocturnal hypoxemia: results from the Swedish CArdioPulmonary bioimage Study (SCAPIS) – a cross-sectional study

Obstructive sleep apnoea (OSA) and its associations with lung function.BackgroundOSA is highly prevalent and characterised by abnormal respiration during sleep. This large, population-based study aimed to investigate the associations between OSA and lung function in subjects aged 50–64 years.MethodThe population-based Swedish CArdioPulmonary bioimage Study includes information on anthropometry, comorbidities and spirometry. The current analysis included data from three centres (Gothenburg, Umeå and Uppsala) on whole-night respiratory polygraphy as a meta-analysis examining the overall effect size of lung function on sleep apnoea severity, expressed as ß-coefficient after stratifying for sex and adjusting for age, waist circumference and smoking status.ResultsData from9016participants (54%women, age58±4 years, body mass index27±4 kg/m2) with sleep recordings of good quality were included in the final analysis. Forced expiratory volume during1 s(FEV1) (ß=−0.10 (95% CI −0.16 to −0.03)),forced vital capacity(FVC) (−0.15 (−0.21 to −0.10)) anddiffusion capacity for carbon monoxide(DLCO) (−0.08 (−0.10 to −0.05)) were all negatively associated with theoxygen desaturation index(ODI) and also with per cent of registration with nocturnal oxygen saturation&lt;90% FVC(−0.44 (−0.87 to −0.01)), FEV1(−0.86 (−1.36 to −0.36)) and DLCO(−0.47 (−0.60 to −0.35)). Additionally, a positive association was observed between FEV1(0.13 (0.05 to 0.22)) and DLCO(0.07 (0.04 to 0.09)) with the mean nocturnal saturation. There was a negative association between DLCOandapnoea-hypopnoea index, AHI, (ß=−0.04 (95% CI−0.06 to −0.03)), while no associations were found between FEV1or FVC and AHI.ConclusionIn OSA, lower lung function is more distinctly associated with the nocturnal hypoxic burden than AHI. Potential lung function impairment should be investigated in OSA patients with a high ODI relative to AHI.

Sleep quality in glaucoma patients

The purpose of this study is to objectively assess by polysomnography total sleep time and sleep macrostructure in glaucomatous versus non-glaucomatous individuals after adjusting for possible confounding factors affecting the quality of sleep. This is an observational, prospective, single-center, case-controlled study using a sleep research database (MARS e-Cohort) collecting clinical data, comorbidities, medications, and sleep studies of glaucomatous and non-glaucomatous individuals. The diagnosis of glaucoma was confirmed with a full comprehensive ophthalmological examination including a visual field test. Total sleep time and the main sleep parameters (time spent in stages 1, 2, 3 and 4, microarousals, apnea–hypopnea index, and indices of hypoxic burden) were compared in glaucomatous and non-glaucomatous individuals after adjusting for age, anthropometric data, and comorbidities. The study included 33 glaucomatous and 66 non-glaucomatous individuals. The median total sleep time was 325 min [273; 398] for the control group and 311 min [244; 349] for the glaucoma group. After adjusting for the potential confounding factors, there was no significant difference in total sleep time (p = 0.3) and other sleep parameters between the control group and the glaucoma group. The sleep macrostructure was comparable in the glaucomatous and non-glaucomatous individuals after careful adjustment for confounders.

Sleep apnea physiological burdens and markers of white matter injury: the Multi-Ethnic Study of Atherosclerosis.

Obstructive sleep apnea (OSA) is associated with cognitive impairment; however, the underlying mechanisms remain incompletely understood. OSA is characterized by periods of interrupted ventilation ("ventilatory burden (VB)"), leading to hypoxemia ("hypoxic burden (HB)") and/or arousal ("arousal burden (AB)") from sleep. While hypoxemia is considered a key mechanism underlying white matter injury, its measurement has been limited. In our primary analysis, we assessed the association of HB, a quantitative measure of hypoxemia, with white matter hyperintensity volume (WMHv), a marker of small vessel disease, and compared with that of VB and AB (quantitative measures of ventilatory deficit and arousals). Data from participants in the Multi-Ethnic Study of Atherosclerosis with full polysomnograms (PSG) and brain MRI were analyzed. HB was defined as the total area under the oxygen desaturation curve per hour of sleep, while VB was defined as the event-specific area under the ventilation signal and AB was defined as the normalized cumulative duration of all arousals. The primary outcome was WMHv, with other MRI measures considered secondary outcomes. The analysis included PSGs from 587 participants (age: 65.5±8.2 years). In the fully adjusted model, each 1 standard deviation (SD) increase in HB was associated with a 0.09 SD increase in WMHv (p=0.023), after adjusting for demographics, study site, and comorbidities. In contrast, VB, AB, and conventional OSA measures were not associated with outcomes. Hypoxic burden was associated with white matter hyperintensity volume in a racially/ethnically diverse cohort of older individuals with a high prevalence of OSA.

Atomoxetine and spironolactone combine to reduce obstructive sleep apnea severity and blood pressure in hypertensive patients.

Norepinephrine reuptake inhibitors such as atomoxetine (ato) can improve OSA by increasing pharyngeal muscle activity. Mineralocorticoid antagonists such as spironolactone, may potentiate the reduction of OSA severity and reduce blood pressure. We evaluated whether adding spironolactone to atomoxetine (ato-spiro) improved responses in hypertensive OSA patients. Twenty-one patients with an apnea-hypopnea index (AHI) between 10 and 50 events/h and a history of hypertension were recruited and crossed-over in random order to ato 80mg and ato-spiro 80/50mg for 1 week after a 3-day low dose run-in period. Two dropped out due to drug related side effects. Polysomnography and 24-hour blood pressure (BP) monitoring were performed at baseline and after each treatment period. AHI decreased on both ato and ato-spiro from a baseline median(IQR) of 20.3(18.8 to 28.5) to 8.2(7 to 13.1) and 6.2(5.7 to 14.1), respectively (p < 0.001 for both). Systolic BP (mmHg) fell by mean(95%CI) -4.5(-13.8 to 4.8, p = 0.33) on ato and - 10.3(-19.2 to -1.5, p = 0.02) on ato-spiro, and diastolic BP dropped by -3.0(-8.0 to 2.0, p = 0.23) on ato and - 5.0(-9.1 to -0.9; p = 0.02) on ato-spiro. Both ato and ato-spiro led to a significant shift from apnea to hypopnea predominance (p < 0.001), and significant reductions in hypoxic burden (p ≤ 0.001) and REM sleep (p ≤ 0.001). Both ato-spiro and ato alone decreased OSA severity similarly, but ato-spiro led to even greater, statistically significant and clinically meaningful falls in systolic and diastolic BP. BP reductions were likely due to ato-related improvements in upper airway patency and hypoxemia, and to spiro-related reduced fluid retention. These findings show promise for ato-spiro as an oral treatment for hypertensive OSA patients. REGISTERED AT CLINICALTRIALS.GOV: NCT04905979.

OSA Symptom Subtypes and Hypoxic Burden Independently Predict Distinct Cardiovascular Outcomes

Study ObjectivesStudies on obstructive sleep apnea (OSA) have identified clinically relevant symptom-based subtypes and novel OSA-specific nocturnal hypoxic measures. Both traits are individually associated with cardiovascular outcomes, but evidence about their independent or shared effects is unknown. This study investigated the simultaneous contributions of OSA symptom subtypes and hypoxic burden (HB) on incident cardiovascular outcomes.MethodsSleep Heart Health Study participants with high-quality oxygen saturation, apnea-hypopnea index (AHI), and symptom data were included. Participants with OSA (AHI≥5 events/hour) were grouped into symptom subtypes. HB was calculated from respiratory event-related hypoxia. Cox proportional hazards models assessed whether symptom subtypes and/or HB were independently associated with cardiovascular mortality and major adverse cardiovascular events (MACE).Results4396 participants free of cardiovascular disease were analyzed, with median follow-up &gt;11 years. Higher HB was associated with worse cardiovascular mortality (HR [95% CI]: 1.63 [1.13,2.35]; p=0.009) independently of symptom subtypes. Compared to those without OSA, the excessively sleepy OSA subtype had higher risk of incident MACE (1.62 [1.23,2.15]; p&lt;0.001), independently of HB. Among participants with moderate-severe OSA (AHI ≥15 events/hour), excessively sleepy participants had higher risk of cardiovascular endpoints compared to other subtypes, but HB was not associated with cardiovascular mortality or MACE risk.ConclusionOSA symptom subtypes and HB are independently associated with MACE and cardiovascular mortality, respectively. Thus, both are important for understanding OSA-related cardiovascular risk. Future studies using clinical samples including OSA therapy information that incorporate symptom subtypes and novel biomarkers, such as HB, could improve predictive models for cardiovascular disease risk.

Sleep apnea-specific hypoxic burden and pulse rate response in children using high flow nasal cannula therapy compared with continuous positive airway pressure

BackgroundElevated sleep apnea-specific hypoxic burden (HB) and pulse rate response (ΔHR) are associated with a higher cardiovascular risk in adults. The clinical significance of HB and ΔHR in children with obstructive sleep apnea (OSA) and their responses to therapy have not yet been investigated. This study aimed to compare the efficacy of high flow nasal cannula (HFNC) and continuous positive airway pressure (CPAP) in reducing HB and ΔHR in children. MethodsThis analysis included 17 children (11 males, mean age: 12.6 ± 3.9 years) with obesity and/or medical complexity and moderate-to-severe OSA. Each participant underwent two additional sleep studies: one for HFNC titration and another for CPAP titration. HB and ΔHR were derived from the oximetry and pulse rate signals from overnight sleep studies, respectively. ResultsBoth HFNC and CPAP demonstrated significant reductions in HB from baseline, with similar magnitudes [HFNC: −129 (standard error, SE 55) %min/h, p = 0.003; CPAP: −138 (SE 53) %min/h, p = 0.005]. However, for ΔHR, a significant reduction from baseline was observed only in the CPAP group [–2.7 (SE 1.1) beats/min, p = 0.049], not the HFNC group [–1.0 (SE 1.4) beats/min, p = 0.67]. ConclusionsHFNC is as effective as CPAP in treating hypoxia in children with OSA, but HFNC might be less effective than CPAP in mitigating cardiovascular stress from autonomic disturbances during obstructive events.

Hypoxic burden - definitions, pathophysiological concepts, methods of evaluation, and clinical relevance.

Obstructive sleep apnea (OSA) is a common chronic condition that affects over a billion people worldwide and is associated with adverse cardio- and cerebrovascular consequences. Currently, the go-to clinical measure that determines the presence and severity of OSA is the apnea-hypopnea index (AHI). The AHI captures the frequency of respiratory events due to changes in ventilation that are associated with either oxygen desaturations or arousal from sleep. The AHI is poorly correlated to adverse outcomes in OSA with poor prognostic ability. To overcome the limitations of AHI and perhaps driven by the ease of acquisition, several studies have suggested characterizing nocturnal hypoxia in OSA, termed as "hypoxic burden". The purpose of this review is to focus on the hypoxic burden in OSA, its various definitions, and its utility in moving OSA diagnosis beyond the AHI. Several measures and definitions of hypoxic burden have been proposed and studied that show promise in overcoming limitations of AHI and also have a greater prognostic ability than AHI. More recently, area-based measures that attempt to characterize the depth and duration of oxygen desaturations, i.e., nocturnal hypoxia in OSA, have been shown to better relate to incident cardiovascular disease than AHI. In this review, we delve into the evidence for these novel area-based metrics and also delve into the pathophysiological concepts underlying nocturnal hypoxia while cautioning the reader on interpretation of the recent findings relating hypoxic burden to adverse outcomes in OSA. In this review on hypoxic burden, we focus on the need that has driven the sudden influx of studies assessing hypoxic burden for various outcomes of OSA, its underlying pathophysiology, the various definitions, and clinical relevance. We hope that the reader can appreciate the nuances underlying hypoxic burden in OSA and suggest the need for a cohesive framework for moving beyond the AHI with hypoxic burden.

Morphological Prediction of CPAP Associated Acute Respiratory Instability.

Multiple mechanisms are involved in the pathogenesis of obstructive sleep apnea (OSA). Elevated loop gain is a key target for precision OSA care and may be associated with treatment intolerance when the upper airway is the sole therapeutic target. Morphological or computational estimation of LG is not yet widely available or fully validated - there is a need for improved phenotyping/endotyping of apnea to advance its therapy and prognosis. This study proposes a new algorithm to assess self-similarity as a signature of elevated loop gain using respiratory effort signals and presents its use to predict the probability of acute failure (high residual event counts) of continuous positive airway pressure (CPAP) therapy. Effort signals from 2145 split-night polysomnography studies from the Massachusetts General Hospital were analyzed for SS and used to predict acute CPAP therapy effectiveness. Logistic regression models were trained and evaluated using 5-fold cross-validation. Receiver operating characteristic (ROC) and precision-recall (PR) curves with AUC values of 0.82 and 0.84, respectively, were obtained. Self-similarity combined with the central apnea index (CAI) and hypoxic burden outperformed CAI alone. Even in those with a low CAI by conventional scoring criteria or only mild desaturation, SS was related to poor therapy outcomes. The proposed algorithm for assessing SS as a measure of expressed high loop gain is accurate, non-invasive, and has the potential to improve phenotyping/endotyping of apnea, leading to more precise sleep apnea treatment strategies.

Hypoxic burden and sleep hypoventilation in obese patients

IntroductionNovel biomarkers of hypoxic load have emerged, as sleep apnea-specific hypoxic burden which provides more precise assessment of intermittent hypoxemia severity. Our main objective was to assess the potential benefit of hypoxic burden to identify obesity-related sleep hypoventilation. We hypothesized that hypoxic burden may help diagnose obesity-related sleep hypoventilation better than usual sleep respiratory measures (i.e., apnea-hypopnea index (AHI), mean SpO2, time with SpO2 < 90 %). MethodsThis retrospective study was conducted from June 2022 to October 2023 at the University Hospital of Rouen, France. All consecutive obese patients (BMI ≥30 kg/m2), adults, with no other respiratory or neurological diseases who underwent a polysomnography or polygraphy with concomitant capnography were included. Sleep hypoventilation was defined according to American Academy of Sleep Medicine criteria based on transcutaneous CO2 monitoring (PtcCO2). Diagnostic performance of sleep-related respiratory measures i.e., sleep apnea-specific hypoxic burden, apnea-hypopnea index (AHI), mean SpO2, time with SpO2 < 90 % was evaluated using Receiver Operating Characteristic (ROC) curves. Correlations between sleep-related respiratory measures were assessed by a Spearman correlation matrix. ResultsAmong 107 obese patients with analyzed capnography, 37 (35 %) had sleep hypoventilation. Patients were 53 ± 14 years old, mean BMI = 38 ± 6 kg/m2, mean AHI = 26.5 ± 25/h, mean hypoxic burden = 67 ± 109 %min/h, mean SpO2 = 91.5 ± 3 %, mean time with SpO2<90 % = 19.4 ± 28 %, mean PtcCO2 = 6.2 ± 0.7 kPa. A low positive correlation was found between hypoxic burden and mean PtcCO2 (r = 0.4, p < 0.001). Multivariate logistic regression model explaining sleep hypoventilation was insufficient with area under ROC curve of hypoxic burden estimated at 0.74 (95 % CI 0.65 to 0.84). ConclusionHypoxic burden has low correlation with transcutaneous CO2 pressure and a low ability to diagnose obesity-related sleep hypoventilation.

Obstructive Sleep Apnea, Platelet Aggregation, and Cardiovascular Risk.

Although related, the precise mechanisms linking obstructive sleep apnea (OSA) and cardiovascular disease (CVD) are unclear. Platelets are mediators of CVD risk and thrombosis and prior studies suggested associations of OSA and platelet activity. The aim of this study is to assess the link between OSA, platelet activity, and CVD-related risk factors. We studied the association of OSA-measures and platelet aggregation in participants dually enrolled in the SHHS (Sleep Heart and Health Study) and FHS (Framingham Heart Study). We applied linear regression models with adjustment for demographic and clinical covariates and explored interactions with OSA and CVD-related factors, including age, sex, body mass index, hypertension, OSA diagnosis (apnea-hypopnea index 4%≥5), and aspirin use. Our final sample was of 482 participants (60 years [14.00], 50.4% female). No associations were observed between apnea-hypopnea index 4% and platelet aggregation in the main sample. Stratified analysis revealed an association in aspirin users (n=65) for our primary exposure (apnea-hypopnea index 4%, β=0.523; P<0.001; n=65), and secondary exposures: hypoxic burden (β=0.358; P<0.001), minimum saturation (β=-0.519; P=0.026), and oxygen desaturation index 3% (β=74.672; P=0.002). No associations were detected in nonaspirin users (n=417). No associations were detected between OSA and platelet aggregation in a community sample. Our finding that OSA associates with increased platelet aggregation in the aspirin group, most of whom use it for primary prevention of CVD, suggests that platelet aggregation may mediate the adverse impact of OSA on vascular health in individuals with existing CVD risk, supporting further investigation.

Acetazolamide as an Add-on Therapy Following Barbed Reposition Pharyngoplasty in Obstructive Sleep Apnea: A Randomized Controlled Trial.

Surgical interventions, like barbed reposition pharyngoplasty (BRP), are a valuable alternative for patients with obstructive sleep apnea (OSA) who are unable to tolerate continuous positive airway pressure (CPAP). However, predicting surgical success remains challenging, partly due to the contribution of non-anatomical factors. Therefore, combined medical treatment with acetazolamide, known to stabilize respiratory drive, may lead to superior surgical results. This double-blind, parallel-group randomized controlled trial evaluates the efficacy of acetazolamide as an add-on therapy to BRP in OSA. A total of 26 patients with moderate to severe OSA undergoing BRP were randomized to receive either acetazolamide or placebo post-surgery for 16 weeks. The group who was treated with BRP in combination with acetazolamide showed a reduction in AHI of 69.4%, significantly surpassing the 32.7% reduction of the BRP + placebo group (p < 0.01). The sleep apnea-specific hypoxic burden also decreased significantly in the group who was treated with BRP + acetazolamide (p < 0.01), but not in the group receiving BRP + placebo (p = 0.28). Based on these results, acetazolamide as an add-on therapy following BRP surgery shows promise in improving outcomes for OSA patients, addressing both anatomical and non-anatomical factors.

Apnea-Specific Pulse-Rate Response is Associated With Early Subclinical Atherosclerosis in Obstructive Sleep Apnea

IntroductionIn patients with obstructive sleep apnea (OSA), novel metrics such as hypoxic burden (HB) and sleep apnea-specific pulse-rate response (ΔHR) may better correlate with cardiovascular diseases (CVD) than the apnea–hypopnea index (AHI). This manuscript aims to assess the correlation between ΔHR and HB with subclinical atherosclerosis in patients with OSA, testing the hypothesis that elevated ΔHR and HB are associated with subclinical atherosclerosis development. MethodsIn a prospective study, individuals aged 20–65 years with suspected OSA without known comorbidities were consecutively recruited and defined as OSA (AHI≥5events/h) or healthy controls. Using bilateral carotid ultrasonography, common carotid intima-media thickness (CIMT) was assessed and the identification of at least one atheromatous plaque defined the presence of subclinical atherosclerosis. ΔHR, and HB were derived from pulse-oximetry. ResultsWe studied 296 patients of 45±10 years old, of whom 28% were women, and a BMI of 30.3±5.3kg/m2. Overall, 245 had OSA and 51 were healthy controls. After controlling for confounding variables higher ΔHR but not HB, was associated with higher CIMT (p=0.006) and higher time spent with oxygen saturation below 90% (T90) was associated with an increase in carotid atheroma plaques (p=0.032). When stratifying OSA based on HB tertiles, we observed that within tertile 2 of HB, an increase in ΔHR was associated with larger CIMT (p=0.017). ConclusionA higher ΔHR is associated with an increase in CIMT among adult patients with OSA. This study suggests that ΔHR could be a biomarker of risk for CVD in patients with OSA.

Hypoxic indices for obstructive sleep apnoea severity and cardiovascular disease risk prediction: A comparison and application in a community population.

The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) encounter challenges in capturing the intricate relationship between obstructive sleep apnoea (OSA) and cardiovascular disease (CVD) risks. Although novel hypoxic indices have been proposed to tackle these limitations, there remains a gap in comprehensive validation and comparisons across a unified dataset. Samples were derived from the Sleep Heart Health Study (SHHS), involving 4485 participants aged over 40 years after data quality screening. The study compared several key indices, including AHI, ODI, the reconstructed hypoxic burden (rHB), the percentage of sleep time with the duration of respiratory events causing desaturation (pRED_3p) and the sleep breathing impairment index (SBII), in relation to CVD mortality and morbidity risks. Adjusted Cox proportional models were employed to calculate hazard ratios (HRs) for each index, and comparisons were performed. SBII and pRED_3p exhibited significant correlations with both CVD mortality and morbidity, with SBII showing the highest adjusted HR (95% confidence interval) for mortality (2.04 [1.25, 3.34]) and pRED_3p for morbidity (1.43 [1.09-1.88]). In contrast, rHB was only significant in predicting CVD mortality (1.63 [1.05-2.53]), while AHI and ODI did not show significant correlations with CVD outcomes. The adjusted models based on SBII and pRED_3p exhibited optimal performance in the CVD mortality and morbidity datasets, respectively. This study identified the optimal indices for OSA-related CVD risks prediction, SBII for mortality and pRED_3p for morbidity. The open-source online platform provides the computation of the indices.

Independent relationship between sleep apnea-specific hypoxic burden and glucolipid metabolism disorder: a cross-sectional study.

Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown. We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles. The SASHB was independently associated with fasting blood glucose (FBG) (β = 0.058, P = 0.016), fasting insulin (FIN) (β = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.058, P = 0.011), total cholesterol (TC) (β = 0.100, P < 0.001), total triglycerides (TG) (β = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (β = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (β = 0.051, P = 0.049), apolipoprotein B (apoB) (β = 0.136, P < 0.001), apolipoprotein E (apoE) (β = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles. We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA. ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China.

The Hypoxic Burden, Clinical Implication of a New Biomarker in the Cardiovascular Management of Sleep Apnea Patients: A Systematic Review.

Obstructive sleep apnea (OSA) is a highly prevalent sleep-disordered breathing. It is associated with adverse co-morbidities, being the most scientific evidence of cardiovascular (CV) disease. Currently, OSA is measured through the apnea-hypopnea index (AHI), the total number of respiratory events per hour of sleep. However, different studies have questioned its utility in OSA management, highlighting the need to search for new parameters that better reflect the heterogeneity of the disease. Hypoxic burden (HB) has emerged as a novel biomarker that informs about the frequency, duration and depth of the desaturation related to the respiratory events. We conducted a systematic review in order to find publications about the heterogeneity of OSA measured by HB and its associations with future disease. Systematic review was conducted using PubMed and Web of Science. The terms "sleep apne" and "hypoxic burden" were used to look for publications from the date of inception to August 15, 2023. Inclusion criteria: articles in English published in peer-reviewed journals. Exclusion criteria: (1) not available publications; (2) duplicated articles; (3) letters, editorials, and congress communications; (4) articles not including information about HB as a specific biomarker of OSA. 33 studies were included. The results were classified in 2 main sections: (1) HB implication in the CV sphere: HB showed to be a better predictor of CV risk in OSA patients than traditional measures such as AHI with possible clinical management implication in OSA. (2) HB response to OSA treatment: pharmacological and nonpharmacological treatments have demonstrated to be effective in improving hypoxia measured through the HB. HB could be a better and more effective parameter than traditional measurements in terms of diagnosis, risk prediction and therapeutic decisions in patients with OSA. This measure could be incorporated in sleep units and could play a role in OSA management, driving the clinic to a more personalized medicine.

Sleep apnea-related hypoxic burden as a predictor of pregnancy and neonatal outcome

Study objectivesTo determine the clinical impact of sleep apnea-related hypoxic burden in pregnant women and neonates. MethodsThis is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) study. Hypoxia burden was calculated from the home sleep apnea test (HSAT) and defined as the total area under respiratory events. Logistic regression analysis assessed the relationship between hypoxia burden and pregnancy/neonatal outcomes. ResultsA total of 3006 subjects in the early term, and 2326 subjects in the middle term of pregnancy, had HSAT. A hypoxic burden greater than 6.8%min was present in 1740 at early term and associated with a higher risk of preeclampsia (odds ratio 1.297, 95 % confidence interval 1.032–1.630, p: 0.026) after adjusted by obstructive sleep apnea (OSA) severity. In the middle term, 1058 subjects had a hypoxia burden more than 11.8%min, which was a predictor for higher incidence of gestational diabetes (OR 1.795, 95 % CI 1.097–2.938, p: 0.020) and an Apgar <7 at 1 min (OR 1.446, 95 % CI 1.079–1.939, p: 0.012) after adjusted by obstructive sleep apnea (OSA) severity. After adjusted by oxygenation disturbance index, HB was not related with Apgar <7 at 1 min (p:0.565). ConclusionsThe hypoxic burden is an independent predictor for preeclampsia and gestational diabetes and an Apgar <7 at 1 min.

0481 A Novel Phenotype Classification for Obstructive Sleep Apnea Based on Hypoxic Burden

0481 A Novel Phenotype Classification for Obstructive Sleep Apnea Based on Hypoxic Burden

0453 Sleep Apnea-Specific Hypoxic Burden and Delta Heart Rate in Relation to Atrial Fibrillation in a Clinical Cohort

0453 Sleep Apnea-Specific Hypoxic Burden and Delta Heart Rate in Relation to Atrial Fibrillation in a Clinical Cohort

0485 Can Hypoxic Burden Predict Improvement in Sleepiness and Cognition in Response to CPAP Treatment in OSA Patients?

0485 Can Hypoxic Burden Predict Improvement in Sleepiness and Cognition in Response to CPAP Treatment in OSA Patients?