Intermittent Hypoxemia Research Articles

The Effect of Lateral Pharyngeal Collapse Patterns on Therapy Response in Upper Airway Stimulation Surgery.

Obstructive sleep apnea (OSA) is characterized by repeated upper airway collapse while sleeping which leads to intermittent hypoxemia. Upper airway stimulation (UAS) is a commonly practiced modality for treating OSA in patients who cannot tolerate, or do not benefit from, positive airway pressure (PAP). The purpose of this study is to identify the effect of lateral pharyngeal collapse patterns on therapy response in UAS. A retrospective cohort study from a single, tertiary-care academic center was performed. Patients who underwent UAS between October 2016 and July 2019 were identified and analyzed. Drug-induced Sleep Endoscopy (DISE) outcomes between Apnea-Hypopnea Index (AHI) responders and AHI non-responders were compared. Those with complete concentric collapse at the velopharynx were not candidates for UAS. About 95 patients that underwent UAS were included in this study. Pre- to Post-UAS demonstrated significant improvements in Epworth Sleepiness Scale (12.0 vs 4.0, P = .001), AHI (29.8 vs 5.4, P < .001) and minimum oxygen saturation (79% vs 83%, P < .001). No DISE findings significantly predicted AHI response after UAS. Specifically, multiple types of lateral pharyngeal collapse patterns did not adversely effect change in AHI or AHI response rate. Demonstration of lateral pharyngeal collapse on DISE, in the absence of complete concentric velopharyngeal obstruction, does not appear to adversely affect AHI outcomes in UAS patients. VI.

Oxidative Stress Markers among Obstructive Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is a chronic respiratory disorder, which can be present in up to 50% of the population, depending on the country. OSA is characterized by recurrent episodes of partial or complete obstruction of the upper airways with consistent movement of the respiratory musculature during sleep. Apneas and hypopneas can lead to a decrease in oxygen saturation, an increase in carbon dioxide in the blood, and subsequent arousals and sleep fragmentation caused by repetitive activation of the central nervous system. As a consequence, intermittent hypoxemia and consequent reoxygenation result in the production of reactive oxygen species, leading to systematic oxidative stress, which is postulated to be a key mechanism of endothelial dysfunction and increased risk for cardiovascular disorders in patients with OSA. In this review, various biomarkers of oxidative stress, including high-sensitivity C-reactive protein, pregnancy-associated plasma protein-A, superoxide dismutase, cell-free DNA, 8-hydroxy-2-deoxyguanosine, advanced oxidation protein products, lipid peroxidation products, receptor for advanced glycation end-products, and thioredoxin are discussed. Biomarkers of oxidative stress have the potential to be used to assess disease severity and treatment response. Continuous positive airway pressure (CPAP) is one of the most common noninvasive treatments for OSA; it keeps the upper airways open during sleep. This reduces episodes of intermittent hypoxia, reoxygenation, and arousal at night. CPAP has been shown to have anti-inflammatory properties and decrease oxidative stress. The administration of certain compounds, like vitamins A, C, and E as well as N-acetylcysteine and allopurinol, can decrease oxidative stress markers. However, their role in the treatment of OSA remains unclear.

Rationale and design of the Hyperglycemic Profiles in Obstructive Sleep Apnea (HYPNOS) trial

The Hyperglycemic Profiles in Obstructive Sleep Apnea (HYPNOS) randomized clinical trial was conducted in adults with type 2 diabetes and moderate-to-severe obstructive sleep apnea (OSA) to determine whether treatment with positive airway pressure (PAP) therapy is associated with improvements in glycemic measures. Participants were randomly assigned to PAP therapy with lifestyle counseling or lifestyle counseling alone. While observational and experimental evidence indicate that intermittent hypoxemia and recurrent arousals in OSA may alter glucose metabolism and worsen glycemic measures, the effect of treating OSA with PAP therapy on these measures in type 2 diabetes is uncertain. Adequately powered randomized clinical trials have yet to be performed to demonstrate whether PAP therapy for OSA in patients with type 2 diabetes can improve glycemic measures. The HYPNOS trial was designed to determine whether PAP therapy for OSA in patients with type 2 diabetes over 3 months leads to improvements in glycemic measures including glycemic variability (standard deviation) based on Dexcom G4 Platinum continuous glucose monitoring. Secondary objectives were to assess the effects of PAP therapy for OSA on measures of: (1) glycemic variability based on Abbott Freestyle Pro Libre continuous glucose monitoring; (2) point-of-care hemoglobin A1c (HbA1c); (3) degree of post-prandial hyperglycemia as determined by 7-point self-monitoring of blood glucose; (4) clinic and ambulatory blood pressure; and (5) endothelial function. The HYPNOS trial was designed to address gaps in our understanding of the effects of PAP therapy on glucose metabolism in adults with type 2 diabetes and moderate-to-severe OSA.Trial Registration: ClinicalTrials.gov Identifier NCT02454153

Pharmacological inhibition of acetylcholine-regulated potassium current (IK,ACh) and associated A1- and M2-pathways prevent atrial arrhythmogenic changes in a rat model for obstructive sleep apnea

Abstract Background In obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase vagal tone and adenosine release, potentially resulting in an increased acetylcholine-regulated potassium current (IK,ACh). Here we elucidated acute atrial electrophysiological effects of obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) and the role of atrial IKACh activation by A1-receptor and M2-receptor activation. Methods In sedated spontaneously breathing rats (2% isoflurane), either IK,ACh-inhibitor (XAF-1407: 1mg/kg), M2-receptor inhibitor (atropine; 1μg/kg), A1-receptor inhibitor (Rolofylline; 1μg/kg) or a buffer-based vehicle was perfused (Control). INAP was applied non-invasively by a negative pressure device 14 times throughout 70 minutes. Simulated apneas were maintained for one minute with a four minute resting period. Atrial effective refractory period (AERP) and atrial activation time were acquired by a programmed atrial pacing protocol before, during and after applied INAP throughout the study. Results Independent of IK,Ach-inhibition, single INAP applications prolonged transiently atrial activation times (Control: INAP vs. pre-INAP p=0.034; XAF-1407: INAP vs. pre-INAP p=0.039). In control-rats, seventy minutes of repetitive INAP decreased AERP by 15.45±0.06% (vs. baseline p=0.0015), which was reversible upon 1 hour of recovery. AERP shortening correlated with the cumulative pressure applied per body weight (Pearson r=−0.773; p=0.025). Whilst only XAF-1407 and atropine increased baseline AERP, all drug interventions, XAF-1407, atropine and Rolofylline could prevent INAP-associated AERP shortening (end INAP-protocol vs. respective baseline XAF-1407 p=0.994; atropine p=0.984; Rolofylline p=0.951). Drops in oxygen saturation and applied INAP were comparable in all groups. Conclusion Short-term simulated OSA is associated with progressive AERP shortening, which was determined by the cumulative negative airway pressure applied. This potentially represents an important insight in future OSA treatment. Pharmacological IK,ACh inhibition prevented INAP-associated AERP-shortening suggesting an involvement in acute atrial arrhythmogenesis in OSA. However, if IK,Ach and its potential upstream activating A1- and M2-pathway pose a pharmacological treatment target for OSA-patients with AF, requires further investigation. Funding Acknowledgement Type of funding source: None

Dynamic changes in nocturnal blood glucose levels are associated with sleep-related features in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) has a bidirectional relationship with insulin resistance conditions; however, the mechanism remains unclear. This study aimed to compare dynamic nocturnal glucose changes among patients with OSA of varying levels of severity and evaluate temporal changes associated with the cardinal features of OSA (sympathetic hyperactivation, intermittent hypoxemia, and sleep fragmentation) in nondiabetic subjects. Nocturnal glucose was measured with a continuous glucose monitoring device every 5 min during polysomnography (PSG). The OSA features were evaluated using heart rate variability (HRV), minimum saturation, and electroencephalography. Eleven subjects with moderate to severe OSA and 12 subjects with no or mild OSA were evaluated. Those with moderate to severe OSA showed an increasing trend in blood glucose levels after sleep onset, whereas those without or with mild OSA showed a decreasing trend (F = 8.933, p < 0.001). Delta band power also showed different trends during sleep between the two groups (F = 2.991, p = 0.009), and minimum saturation remained lower in the moderate to severe OSA group than in the no or mild OSA group. High degrees of coupling between nocturnal glucose levels and each OSA feature were observed. Altered trends in nocturnal glucose in moderate to severe OSA may reflect glucose intolerance and result in metabolic consequences. Managing the features of sleep-related OSA may have implications for metabolic management in the future.

Impact of obstructive sleep apnea on left ventricular mass index in men with coronary artery disease.

Left ventricular hypertrophy (LVH) is associated with augmented risk for mortality in patients with coronary artery disease (CAD). These patients often have obstructive sleep apnea (OSA). We aimed to evaluate the relationship between OSA and the left ventricular mass index (LVMI) in men with CAD. Consecutive patients with CAD were recruited and underwent overnight portable monitoring for the assessment of OSA. LVMI was ascertained using high-resolution echocardiography. Univariate and multivariate regression analyses were conducted to explore the associations between the OSA parameters and the LVMI levels. Of the 1,053 examined male patients with CAD, 425 (40.4%) had moderate-to-severe OSA (respiratory event index ≥ 15 events/h). The prevalence of LVH (LVMI > 125 g/m²) was 36.0% (n = 379). The mean LVMI values increased with increasing OSA severity (P < .001). Patients with respiratory event index ≥ 30 events/h had 2.30 (95% confidence interval 1.50-3.54, P < .001) times increased risk of LVH than those without OSA (respiratory event index < 5 events/h) independent of confounders. The minimum oxygen saturation levels were the strongest factor correlated with LVMI (β = -0.299, P = .004) of several OSA indices. Patients with minimum oxygen saturation < 70% had an adjusted odds ratio of 3.62 (95% confidence interval 1.81-7.25, P < .001) for LVH development compared with those with minimum oxygen saturation ≥ 90%. OSA severity was associated with a higher likelihood of LVH in men with CAD, which is partially related to severe nocturnal intermittent hypoxemia. Aggressive effort at managing OSA among patients with CAD may further reduce the cardiovascular risk.

Caffeine prophylaxis to improve intermittent hypoxaemia in infants born late preterm: a randomised controlled dosage trial (Latte Dosage Trial)

IntroductionInfants born late preterm (34+0 to 36+6 weeks’ gestational age) have frequent episodes of intermittent hypoxaemia compared with term infants. Caffeine citrate reduces apnoea and intermittent hypoxaemia and improves long-term...

PAY ATTENTION! AN UNUSUAL CASE OF DYSPNEA

SESSION TITLE: Medical Student/Resident Cardiothoracic Surgery Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Platypnea-orthodeoxia is an uncommon syndrome characterized by dyspnea and hypoxemia in upright position that improves with recumbent position. It can occur due to intracardiac shunts, pulmonary arteriovenous shunts and ventilation perfusion mismatch. We present a unique and rare cause of platypnea-orthodeoxia syndrome. CASE PRESENTATION: A 68 years old man with history of coronary artery disease and COPD presented with acute onset chest pain and associated difficulty breathing. Patient did have several months’ history of exertional dyspnea which did not improve with rest this time. On presentation, patient was noted to be hypoxic with oxygen saturation of 88% and ABG showed PH 7.41, PaO2 47 mmHg and PaCO2 22.4 mmHg. Oxygen saturation improved to 94% with 3L of supplemental oxygen. EKG and troponin were unremarkable. CT PE was unremarkable for pulmonary embolism as well. IV heparin drip was started for suspected unstable angina and patient underwent cardiac catheterization that revealed non-obstructive coronary artery disease. Echocardiography showed ejection fraction of 55-60% with mild mitral and tricuspid regurgitationDuring the course of hospitalization, patient was noted to have intermittent positional hypoxemia. He had normal resting saturation on 2 L of oxygen which dropped to 88% sitting upright and dropped to 84% on 2 L of oxygen upon raising both arms. Platypnea-orthodeoxia syndrome was strongly suspected with possible intra-cardiac or intrapulmonary shunt. Meanwhile, CT chest was unremarkable for interstitial lung disease. Right heart catheterization revealed normal right atrial RA (68.9%) and pulmonary arterial PA (68.3%) saturation at rest but reduced RA (42.5%) and PA (43.2%) saturation with sitting up. Echocardiography with bubble study showed right-to-left shunting and trans-esophageal echocardiography revealed a small 0.5 cm atrial septal defect (ASD) with bidirectional shunting. Patient was diagnosed with Platypnea-orthodeoxia syndrome secondary to ASD. He was discharged home on supplemental oxygen and outpatient follow-up for ASD closure. DISCUSSION: Platypnea-orthodeoxia is a rare syndrome. Patent foramen ovale is the most common cardiac cause of platypnea-orthodeoxia syndrome followed by ASD. Transesophageal echocardiography is the best test to diagnose atrial septal defect but it is important to rule out pulmonary causes of platypnea-orthodeoxia syndrome as well. ASD is successfully treated with percutaneous closure and prognosis of is good after correction of the defect. CONCLUSIONS: Platypnea-orthodeoxia syndrome is rare syndrome but it can be easily recognized with careful history and physical examination. Reference #1: Henkin S, Negrotto S, Pollak PM, Cullen MW, O'Cochlain DF, Wright RS. Platypnea-Orthodeoxia Syndrome: Diagnostic Challenge and the Importance of Heightened Clinical Suspicion. Tex Heart Inst J. 2015;42(5):498-501. Published 2015 Oct 1. doi:10.14503/THIJ-14-4596 Reference #2: Kazawa S, Enomoto T, Suzuki N, et al. Platypnea-orthodeoxia Syndrome in a Patient with an Atrial Septal Defect: The Diagnosis and Choice of Treatment. Intern Med. 2017;56(2):169-173. doi:10.2169/internalmedicine.56.7728 Reference #3: PLATYPNEA ORTHODEOXIA SYNDROME: A RARE COMPLICATION OF IATROGENIC ATRIAL SEPTAL DEFECT. Bharat Avirneni, Christopher Rosse, Joseph Choo, Kalpan Desai. J Am Coll Cardiol. 2020 Mar, 75 (11 Supplement 1) 2799. DISCLOSURES: No relevant relationships by Muhammad Aamir, source=Web Response No relevant relationships by Muhammad Afzal, source=Web Response No relevant relationships by Saleha Dar, source=Web Response

Effects of β-adrenergic stimulation on fetal heart rate, heart rate variability, and T-wave elevation during brief umbilical cord occlusions in fetal sheep.

Circulating catecholamines are critical for fetal adaptation to hypoxia by regulating fetal heart rate (FHR) and promoting myocardial contractility and peripheral vasoconstriction. They have been hypothesized to contribute to changes in FHR variability (FHRV) and T-wave morphology, clinical indexes of fetal well-being during labor. β-Adrenergic blockade with propranolol does not affect FHRV during labor-like hypoxemia and only attenuated the increase in T-wave height between the episodes of hypoxemia. To further investigate the potential role of catecholamines, we investigated whether pharmacological β-adrenergic stimulation could increase FHRV and T-wave elevation during intermittent labor-like hypoxemia. Nineteen chronically instrumented fetal sheep at 0.85 of gestation received isoprenaline hydrochloride (n = 7) or saline (control, n = 12), followed by three 1-min complete umbilical cord occlusions (UCOs) separated by 4-min reperfusion periods. Before the UCOs, infusion of isoprenaline increased FHR (P < 0.001), absolute-T/QRS ratio (P < 0.001), and one measure of FHRV [root-mean-square of successive RR interval differences (RMSSD), P < 0.05]. UCOs triggered deep FHR decelerations. During UCOs, isoprenaline was associated with increased FHR (P < 0.001) and absolute-T/QRS ratio (P < 0.05), but no effect on T/QRS ratio was observed when normalized to baseline before UCOs (normalized-T/QRS ratio). Between UCOs, isoprenaline increased FHR (P < 0.001) and absolute-T/QRS ratio (P < 0.05) but did not affect normalized-T/QRS ratio or any measures of FHRV. Arterial pressure was not affected by isoprenaline at any point. Our findings indicate that circulating catecholamines regulate FHR but not FHRV during labor-like hypoxemia and promote T-wave elevation between but not during intermittent fetal hypoxemia.

Dysfunction in Automatic Processing of Emotional Facial Expressions in Patients with Obstructive Sleep Apnea Syndrome: An Event-Related Potential Study.

AimObstructive sleep apnea syndrome (OSAS) is a prevalent chronic disease characterized by sleep fragmentation and intermittent hypoxemia. Several studies suggested that electrophysiological changes and neurocognitive abnormalities occurred in OSAS patients. In this study, we compared automatic processing of emotional facial expressions schematic in OSAS patients and matched healthy controls via assessing expression-related mismatch negativity (EMMN).MethodsTwenty-two OSAS patients (mean age 44.59 years) and twenty-one healthy controls (mean age 42.71 years) were enrolled in this study. All participants underwent Montreal Cognitive Assessment (MoCA) scale test and polysomnographic recording. An expression-related oddball paradigm was used to elicit EMMN and the electroencephalogram was recorded and analyzed. Furthermore, Pearson’s correlations were calculated to discuss the correlation between neuropsychological test scores, clinical variables and electrophysiological data.ResultsCompared with healthy controls, OSAS sufferers demonstrated significantly reduced EMMN mean amplitudes within corresponding time intervals, regardless of happy or sad conditions. Meanwhile, we observed that amplitude of sad EMMN was larger (more negative) than happy EMNN in healthy controls, while not in patients. Moderate correlations were found between MoCA test scores, sleep parameters and EMMN amplitudes.ConclusionOur findings suggested pre-attentive dysfunction of processing emotional facial expressions in patients with OSAS, without the existence of negative bias effect. Moreover, correlation analysis showed that clinical characteristics of OSAS patients could affect EMMN amplitudes. Further studies on the advantages of EMMN as clinical and electrophysiological indicators of OSAS are warranted.

Troubles urinaires et génito-sexuels dans le syndrome d’apnée obstructive du sommeil : revue de la littérature

The objective of this work was to make a review of urinary tract symptoms and erectile dysfunction involved in obstructive sleep apnea (OSA) but also to study their physiopathology and potential treatments. We conducted a literature review in the Pubmed database using PRISMA guidelines and the MeSH terms: sleep apnea, urinary incontinence, erectile dysfunction, sexuality. All French and English articles published up to 2020 were evaluated. The initial evaluation identified 240 articles from which 30 were included. References lists review allowed the inclusion of 26 additional articles. Nocturia, overactive bladder (OAB) and erectile dysfunction (ED) were associated with OSA. Increased levels of natriuretic peptides are behind nocturia. Nocturia is associated with higher Apnea/Hypopnea Index (AHI) (49±11 vs 24±8 episodes/hour with P=0.0001). The severity of nocturia is proportional to the severity of OSA with a positive predictive value of 71%. Intermittent nocturnal hypoxemia causes peripheral axonal damage with subsequent urgency incontinence. There is correlation between severity of OAB and the severity of OSA especially when the latter is moderate or severe. An odds ratio of 0.45 (CI95%: 0.18-0.71) is found for ED in patients who don't have OSA, associating the latter to an increased risk of ED. Intermittent nocturnal hypoxemia, the decrease in the levels of nitric oxide, and the increase in blood pressure and levels of endothelin 1 contribute to the development of ED. An early treatment of OSA with continuous positive airway pressure (CPAP) may allow a partial but significant control of urinary symptoms and erectile dysfunction associated with OSA. OSA is associated with urinary tract symptoms (nocturia and OAB) and erectile dysfunction. The severity of associated symptoms is related to the severity of OSA. Urinary and sexual troubles are reversible after treatment of OSA by CPAP. OSA research is reasonable in case of pathologic nocturia or ED with loss of morning erections.

The Relationship between Oxidative Stress, Intermittent Hypoxemia, and Hospital Duration in Moderate Preterm Infants

Introduction: Lipid peroxidation products are present following oxidation of polyunsaturated fatty acids in the eye, brain, and various cell membranes. Elevated levels of lipid peroxidation products and increased intermittent hypoxemia (IH) events have been associated with adverse outcomes in extremely preterm infants. The moderate preterm newborn has a still-developing oxidant defense system and immature respiratory control, but little is known about lipid peroxidation levels and IH in this larger and more common preterm population. Objective: To determine the association between oxidative stress and IH in moderate preterm infants. Method: Oxygen saturation was continuously monitored in 51 moderate preterm infants (i.e., 31 + 0/7 to 33 + 6/7 weeks’ gestation). Urine samples were collected at the end of the first and second weeks of life. Samples were analyzed for total lipid peroxidation products (neurofurans, isofurans, neuroprostanes, isoprostanes, and di-homo-isofurans). Result: At week 1, there was a correlation between increased IH frequency and neurofurans (p < 0.04) and di-homo-isofurans (p < 0.003). At week 2, there was no correlation between IH and lipid peroxidation markers. Ele­vations in neurofurans, isofurans, neuroprostanes, and di-homo-isofurans in the first and/or second week of life were associated with a longer stay in hospital. Conclusion: Elevations in lipid peroxidation biomarkers in moderate preterm infants during their first weeks of life are associated with a higher frequency of IH and prolonged hospitalization.

Aberrant Awake Spontaneous Brain Activity in Obstructive Sleep Apnea: A Review Focused on Resting-State EEG and Resting-State fMRI.

As one of the most common sleep-related respiratory disorders, obstructive sleep apnea (OSA) is characterized by excessive snoring, repetitive apnea, arousal, sleep fragmentation, and intermittent nocturnal hypoxemia. Focused on the resting-state brain imaging techniques, we reviewed the OSA-related resting-state electroencephalogram and resting-state functional magnetic resonance imaging (rsfMRI) studies. Compared with the healthy control group, patients with OSA presented increased frontal and central δ/θ powers during resting-state wakefulness, and their slow-wave activity showed a positive correlation with apnea–hypopnea index. For rsfMRI, the prefrontal cortex and insula may be the vital regions for OSA and are strongly related to the severity of the disease. Meanwhile, some large-scale brain networks, such as the default-mode network, salience network, and central executive network, play pivotal roles in the pathology of OSA. We then discussed the contribution of resting-state brain imaging as an evaluation approach for disease interventions. Finally, we briefly introduced the effects of OSA-related physiological and mental diseases and discussed some future research directions from the perspective of resting-state brain imaging.

SMAD4 Overexpression in Patients with Sleep Apnoea May Be Associated with Cardiometabolic Comorbidities.

Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic and cardiovascular risk. Although the mechanisms involved in the development of these disorders may vary, OSA patients frequently present an increase in transforming growth factor beta (TGFβ), the activity of which is higher still in patients with hypertension, diabetes or cardiovascular morbidity. Smad4 is a member of the small mother against decapentaplegic homologue (Smad) family of signal transducers and acts as a central mediator of TGFβ signalling pathways. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with an apnoea–hypopnoea index (AHI) ≥30 and 26 healthy volunteers. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in HIF1α, mTOR and circadian genes. Moreover, we associated high concentrations of Smad4 plasma protein with the presence of diabetes, dyslipidaemia and hypertension in these patients. Results suggest that increased levels of SMAD4, mediated by intermittent hypoxaemia and circadian rhythm deregulation, may be associated with cardiometabolic comorbidities in patients with sleep apnoea.

Oxygen desaturation rate as a novel intermittent hypoxemia parameter in severe obstructive sleep apnea is strongly associated with hypertension.

To investigate the effects of different intermittent hypoxemia properties on blood pressure (BP) and short-term blood pressure variability (BPV) in severe obstructive sleep apnea (OSA) patients. Nocturnal BP was continuously monitored by measuring pulse transmit time. Apnea-related systolic BP elevation values were used to reflect BPV. Beat-to-beat R-R interval data were incorporated in polysomnography for heart rate variability analysis. The low-frequency/high-frequency band ratio was used to reflect sympathovagal balance. The rate of pulse oxyhemoglobin saturation (SpO₂) decrease was counted as the change in the percentage of SpO₂ per second after obstructive apnea and expressed as the oxygen desaturation rate (ODR). Patients with severe OSA (n = 102) were divided into 2 groups according to the median ODR: faster ODR (FODR group: ODR > 0.37, n = 50) and slower ODR (ODR ≤ 0.37, n = 52). Comparisons between the 2 groups showed significantly higher systolic BP (SBP) values in the FODR group than in the slower ODR group (awake SBP 149.9 ± 18.3 vs 131.8 ± 15.6 mm Hg; asleep SBP: 149.6 ± 19.9 vs 128.7 ± 15.6 mm Hg; both P < .001), as well as short-term BPV (15.0 ± 4.8 vs 11.6 ± 3.6 mm Hg; P < .001), and the prevalence of hypertension (74.0% vs 26.9%; P < .001). Multiple linear regression analyses revealed that after adjusting for body mass index, functional residual capacity, expiratory reserve volume, and baseline SpO2, ODR, as assessed by ΔSpO₂/Δt, had the strongest association with both BP and short-term BPV. Correlation analysis showed that ODR was positively correlated with the low-frequency/high-frequency band ratio (r = .288, P = .003). ODR, as a novel hypoxemia profile, was more closely associated with the elevation of BP and BPV in patients with severe OSA. FODR might be associated with enhanced sympathetic activity. Registry: ClinicalTrials.gov; Name: Characteristics of Obstructive Sleep Apnea Syndrome Related Hypertension and the Effect of Continuous Positive Airway Pressure Treatment on Blood Pressure; URL: https://clinicaltrials.gov/ct2/show/NCT03246022; Identifier: NCT03246022.

When will we ditch the AHI?

When will we ditch the AHI?

Can Long-term Treatment of Obstructive Sleep Apnea With CPAP Improve Glycemia and Prevent Type 2 Diabetes?

Obstructive sleep apnea (OSA) is a prevalent sleep disorder caused by intermittent partial or complete collapse of the upper airway during sleep resulting in intermittent hypoxemia and hypercapnia, sleep fragmentation, increased oxidative stress, and systemic inflammation. The prevalence of moderate-to-severe OSA in the general population, estimated at 23.4% in women and 49.7% in men, has increased over the past few decades (1,2), due in part to the obesity epidemic (3). Multiple observational studies have reported an association between OSA, insulin resistance, and increased risk of incident type 2 diabetes (4,5). In a meta-analysis, the presence of OSA was independently associated with a 1.35-fold increase in the risk of developing type 2 diabetes (4). In addition to being a risk factor for developing type 2 diabetes, OSA is highly prevalent in adults with type 2 diabetes, with prevalence estimates between 58% and 86%, with moderate-to-severe OSA being present in 25–59% of individuals (4). Although increasing severity of OSA has been associated with worsened glycemic control (6), continuous positive airway pressure (CPAP), the gold standard treatment of OSA, has not been consistently shown to improve glycemic control or reduce insulin resistance in clinical trials in which CPAP was used for 1–6 months (4,7–10). Multiple factors may contribute to the heterogeneity of the results, including different levels of CPAP adherence, various durations of CPAP therapy, background glycemic control, and the use of antihyperglycemic agents, the number of which has been ever increasing. In well-controlled laboratory experiments, however, there is evidence that short-term CPAP use with ensured compliance of 8 h nightly for 1–2 weeks results in improved …

Intermittent Hypoxemia in Preterm Infants: A Potential Proinflammatory Process.

A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants. Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation. A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56-0.74, all p < 0.01). We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process. · IH events are common.. · IH is associated with elevated C-reactive protein.. · Longer IH events (>1 min) are of most significance..

PREVALENCE, CHARACTERISTICS, AND ASSOCIATION OF OBSTRUCTIVE SLEEP APNEA (OSA) AND INTERMITTENT HYPOXEMIA WITH COGNITIVE FUNCTION IN PATIENTS WITH MILD-MODERATE ALZHEIMER DISEASE (AD)

TYPE: Abstract Publication TOPIC: Sleep Disorders PURPOSE: Analysis of several prospective populational studies had indicated that those subjects with OSA were more likely to develop cognitive impairment and AD. However, poor is known about the implications of OSA and intermittent hypoxemia in patients with early AD. The aim of this work was to evaluate the prevalence of OSA in patients with a new diagnosis of mild-moderate AD and to evaluate the repercussion on cognitive function. METHODS: We included prospectively 128 subjects with new diagnosis of AD, stratified by their apnea/hypoapnea index evaluated by polysomnography. Subjects were studied by means of a sleep questionnaire that included the Epworth scale and extensive neuropsychological battery RESULTS: Prevalence of OSA was 90,6%. According the severity of OSA, 23% were mild, 29% moderate and 39% severe. The score on the Epworth scale was 5.66, without significant differences between groups (p>0.05). We evaluated the characteristics of cognition according to the severity of OSA. No statistically significant differences were observed. Given oxygen desaturation severity, we observed that patients with severe intermittent hypoxemia showed better cognitive performances in overall items related to verbal memory (Table 1) When we analysed intermittent hypoxia data by gender groups, all differences were observed in female group CONCLUSIONS: High prevalence of no diagnosed OSA in patients with a new diagnosis of AD. This prevalence is not related with an increase of diurnal somnolence. Severe intermittent hypoxemia seems related with a better neuropsychological profile in several cognitive domains. CLINICAL IMPLICATIONS: Maybe, chronic hypoxia throw the phenomenon of ischemic tolerance could have a benefit effect. DISCLOSURE: No significant relationships. KEYWORDS: OSA, Intermittent hypoxia, Alzheimer Disease

741Pharmacological inhibition of the acetylcholine-regulated potassium channel (IK,ACh) prevents atrial arrhythmogenic changes in a rat model for obstructive sleep apnea

Abstract Background In obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase vagal tone, resulting in an increased acetylcholine-regulated potassium current (IK,ACh). Here we elucidated acute atrial electrophysiological effects of obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) and the role of atrial IKACh activation. Methods In sedated spontaneously breathing rats (2% isoflurane), either IK,ACh-inhibitor (XAF-1407: 1mg/kg) or a buffer-based vehicle was perfused (Control). INAP was applied non-invasively by a negative pressure device 14 times throughout 70 minutes. Simulated apneas were maintained for one minute with a four minute resting period. Atrial effective refractory period (AERP), inducible atrial fibrillation (AF)-durations and atrial activation time were acquired by a programmed atrial pacing protocol before, during and after applied INAP throughout the study. Results During single INAP applications atrial activation times prolonged transiently in both groups (Control: INAP vs. pre-INAP p = 0.034; XAF-1407: INAP vs. pre-INAP p = 0.039). In control-rats, seventy minutes of repetitive INAP prolonged P-wave duration (+10.8 ± 2.7% vs. baseline, p = 0.008) and decreased AERP by 14.6 ± 3.1% (vs. baseline p = 0.001). AERP shortening correlated with the cumulative pressure applied per body weight (Pearson r= -0.773; p= 0.025). XAF-1407 could prevent P-wave prolongation and AERP shortening. Inducible AF-durations (CTR 0.94 ± 0.34s vs. XAF-1407 0.1 ± 0.09s p = 0.049) were shorter in XAF-1407 treated rats. Drops in oxygen saturation or applied INAP were comparable in control and XAF-1407 rats. Conclusion Short-term simulated OSA is associated with AF-related arrhythmogenic changes, which could be prevented by pharmacological IK,ACh inhibition. Moreover, the cumulative negative airway pressure applied determined aERP shortening and may represent a target for OSA treatment. These findings have important implications for the antiarrhythmic management of AF patients with OSA.