Search

BackgroundObesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions.AimTo examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community.MethodsObese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin.ResultsOut of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST).ConclusionsA defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities.

RATIONALE: Home respiratory polygraphy (HRP) is an alternative to polysomnography (PSG) for sleep apnea-hypopnea syndrome (SAHS) diagnosis. However, therapeutic decision-making is a different process than diagnosis. OBJECTIVES: This study aimed to determine the agreement between HRP and in-hospital PSG for therapeutic decision-making in a large sample. METHODS: Patients with an intermediate or high SAHS suspicion were included in a multicenter study (eight sleep centers) and assigned to home and hospital protocols in a random order. Therapeutic decisions (continuous positive airway pressure, no continuous positive airway pressure, or impossible decision) were made by an investigator in each center, based on using either HRP or PSG and a single set of auxiliary clinical variables. Patients and diagnostic methods (HRP and PSG) were assessed in random order using an electronic database. After a month the same therapeutic decision-making procedure was repeated with the same method. MEASUREMENTS AND MAIN RESULTS: Of 366 randomized patients, 348 completed the protocol. The 'impossible decision' case was not observed with either PSG or HRP. Therapeutic decisions using HRP had a sensitivity of 73%, a specificity of 77%, and an agreement level (sum of true positives and negatives) of 76%. Patients with higher HRP apnea-hypopnea index (AHI) scores (>= 30; 41% of the total sample) had a sensitivity of 94%, a specificity of 44%, and the agreement level was 91%. CONCLUSIONS: The HRP-based therapeutic decision was adequate when AHI was high, but deficient in the large population of patients with mild to moderate AHI. Therefore, both selecting patients with a high suspicion and severity of SAHS and future prospective cost-effectiveness studies are necessary. [ABSTRACT FROM AUTHOR]

Rationale: Although obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated., Objective: To characterize the molecular pathways that relate OSA with CVE recurrence., Methods: This post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea-hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology., Results: Proteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m 2 ). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes., Conclusion: A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Hypoxic burden (HB) has emerged as a strong predictor of cardiovascular risk in obstructive sleep apnoea (OSA). We aimed to assess the potential of HB to predict the cardiovascular benefit of treating OSA with continuous positive airway pressure (CPAP)., Methods: This was a post hoc analysis of the ISAACC trial (ClinicalTrials.gov: NCT01335087) including non-sleepy patients with acute coronary syndrome (ACS) diagnosed with OSA (apnoea-hypopnoea index ≥15 events·h -1 ) by respiratory polygraphy. Patients were randomised to CPAP or usual care and followed for a minimum of 1 year. HB was calculated as the total area under all automatically identified desaturations divided by total sleep time. Patients were categorised as having high or low baseline HB according to the median value (73.1%min·h -1 ). Multivariable Cox regression models were used to assess whether the effect of CPAP on the incidence of cardiovascular outcomes was dependent on the baseline HB level., Results: The population (362 patients assigned to CPAP and 365 patients assigned to usual care) was middle-aged (mean age 59.7 years), overweight/obese and mostly male (84.5%). A significant interaction was found between the treatment arm and the HB categories. In the high HB group, CPAP treatment was associated with a significant reduction in the incidence of cardiovascular events (HR 0.57, 95% CI 0.34-0.96). In the low HB group, CPAP-treated patients exhibited a trend toward a higher risk of cardiovascular outcomes than those receiving usual care (HR 1.33, 95% CI 0.79-2.25). The differential effect of the treatment depending on the baseline HB level followed a dose-response relationship., Conclusion: In non-sleepy ACS patients with OSA, high HB levels were associated with a long-term protective effect of CPAP on cardiovascular prognosis., Competing Interests: Conflict of interest: M.Á. Martinez-Garcia received grants from VitalAire and Philips, Spain, and serves as a consultant for ResMed Inc., Australia, companies that develop products related to sleep apnoea. L. Messineo received a consultancy fee from Apnimed. A. Wellman works as a consultant for Apnimed, SomniFix and Nox, and has received grants from SomniFix and Sanofi; A. Wellman has a financial interest in Apnimed, a company developing pharmacological therapies for sleep apnoea. His interests were reviewed and are managed by Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict of interest policies. S. Redline received grant support and consulting fees from Jazz Pharmaceuticals, and consulting fees from Apnimed and Lilly Pharma. S. Sands receives personal fees as a consultant for Nox Medical and Merck, outside the submitted work, and receives grant support from Apnimed and ProSomnus. F. Barbé received a research grant from ResMed Inc., Australia, a company that develops products related to sleep apnoea. A. Azarbarzin reports grant support from SomniFix and serves as a consultant for SomniFix, Respicardia, Eli Lilly and Apnimed. Apnimed is developing pharmacological treatments for obstructive sleep apnoea. A. Azarbarzin's interests were reviewed by Brigham and Women's Hospital and Mass General Brigham in accordance with their institutional policies. All other authors declare no competing interests., (Copyright ©The authors 2023.)

Background: Obstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases., Methods: This post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24-72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE., Results: We included 86 patients (median age: 61 years, median BMI: 29.4 kg/m 2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71-0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems., Conclusion: In ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management., Competing Interests: Conflict of interest statement FB received a research grant from ResMed (an Australian company that develops products related to sleep apnea), the Health Research Fund, the Spanish Ministry of Health, the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin (Spain), Oxigen Salud (Spain), and ALLER to develop the ISAACC trial. ResMed partly funded the ISAACC study but did not participate in nor was involved in decisions regarding study development or the present manuscript. All other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Rationale: Obstructive sleep apnea (OSA) is prevalent in patients with acute coronary syndrome (ACS) and is a cause of secondary hypertension. Objectives: To explore the long-term effects of OSA and continuous positive airway pressure (CPAP) treatment on blood pressure (BP) in patients with ACS. Methods: Post hoc analysis of the ISAACC study (Continuous Positive Airway Pressure in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea; NCT01335087) included 1,803 patients admitted for ACS. Patients with OSA (apnea-hypopnea index [AHI], ⩾15 events/h) were randomly assigned to receive either CPAP or usual care and were seen in follow-up for 1-5 years. Office BP was determined at each visit. Results: We included 596 patients without OSA, 978 patients in the usual care or poor CPAP adherence group, and 229 patients in the good CPAP adherence group. At baseline, 52% of the patients were diagnosed with hypertension. Median (25th to 75th percentile) age and body mass index were 59 (52.0 to 67.0) years and 28.2 (25.6 to 31.2) kg/m 2 , respectively. After a median (25th to 75th percentile) follow-up of 41.2 (18.3 to 59.6) months, BP changes were similar in the OSA and non-OSA groups. However, we observed an increase in BP in the third tertile of the AHI (AHI, >40 events/h), with a maximum difference in mean BP of +3.3 mm Hg at 30 months. Patients with OSA with good CPAP adherence (⩾4 h/night) reduced mean BP after 18 months compared with patients with usual care/poor CPAP adherence, with a maximum mean difference (95% confidence interval) of -4.7 (-6.7 to -2.7) mm Hg. In patients with severe OSA, we observed a maximum mean difference of -7.1 (-10.3 to -3.8) mm Hg. Conclusions: In patients with ACS, severe OSA is associated with a long-term increase in BP, which is reduced by good CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT01335087).

Introduction: Obstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS., Methods: Post hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO 2 ), average duration of events and percentage of time with SaO 2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components., Results: From the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO 2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO 2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p -value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events., Conclusion: A RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS., 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 Zapater, Solelhac, Sánchez-de-la-Torre, Gracia-Lavedan, Benitez, Torres, De Batlle, Haba-Rubio, Berger, Abad, Duran-Cantolla, Urrutia, Mediano, Masdeu, Ordax-Carbajo, Masa, De la Peña, Mayos, Coloma, Montserrat, Chiner, Mínguez, Pascual, Cortijo, Martínez, Dalmases, Lee, McEvoy, Barbé, Heinzer and Sánchez-de-la-Torre.)