Effect of 5-year continuous positive airway pressure treatment on MMPs and TIMPs: implications for OSA comorbidities.
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SUBMITTER: Simon B
PROVIDER: S-EPMC7248085 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Effect of 5-year continuous positive airway pressure treatment on MMPs and TIMPs: implications for OSA comorbidities.
Simon Beatrix B Barta Imre I Gabor Bettina B Paska Csilla C Boszormenyi Nagy Gyorgy G Vizi Eva E Antus Balazs B
Scientific reports 20200525 1
Continuous positive airway pressure (CPAP) treatment results in nearly complete remission of symptoms of obstructive sleep apnoea (OSA); however, its effect on OSA comorbidities including cardiovascular diseases remains contradictory. Here we investigated the short- and long-term effect of CPAP treatment on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with severe OSA. Serum levels of 7 MMPs and 3 TIMPs were followed in OSA patients (n = 28) wit ...[more]
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Project description:Study objectivesTo investigate the prevalence of mildly collapsible upper airways (defined by therapeutic continuous positive airway pressure [CPAP] values ≤ 8 cm H₂O) in moderate to severe obstructive sleep apnea patients treated with CPAP and to determine their clinical, functional, and nocturnal polysomnographic characteristics.MethodsEighty-seven patients with moderate to severe obstructive sleep apnea consecutively treated with CPAP were retrospectively investigated. Two nocturnal home sleep portable monitoring studies were performed at baseline and during treatment. Participants were categorized according to therapeutic CPAP values: ≤ 8 cm H₂O (group 1), 8-12 cm H₂O (group 2), ≥ 12 cm H₂O (group 3). Anthropometric, awake respiratory function, symptoms, comorbidities, and nocturnal home sleep portable monitoring studies data were collected.ResultsMild upper airway collapsibility (therapeutic CPAP values ≤ 8 cm H₂O) was present in 25.3% of patients. They showed more favorable apnea-hypopnea index, oxygen desaturation index, mean nocturnal saturation, sleep time with oxygen saturation < 90%, desaturation nadir, and supine position. Oxygen desaturation index showed a weak association with anatomical collapsibility. Using the receiver operating characteristic curve, the area under the curve for the oxygen desaturation index vs CPAP pressure requirements ≤ 8 cm H₂O was low and oxygen desaturation index ≤ 40.8/h showed a sensitivity of 63.3% and a specificity of 69.2% to detect patients with mild collapsibility.ConclusionsA quarter of moderate to severe patients under CPAP therapy had mild collapsibility and were likely to also be good candidates for alternative and better tolerated non-CPAP therapies. Baseline anthropometric, clinical, and respiratory function characteristics did not predict mild upper airway collapsibility determined by CPAP pressure requirements ≤ 8 cm H₂O.
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Project description:Obstructive sleep apnea (OSA) is associated with increased risk for end-organ morbidities, which can collectively be viewed as accelerated aging. Vascular senescence is an important contributor to end-organ dysfunction. Exosomes are released ubiquitously into the circulation, and transfer their cargo to target cells facilitating physiological and pathological processes. Plasma exosomes from 15 patients with polysomnographically diagnosed OSA at baseline (OSA-T1) after 12 months of adherent continuous positive airway pressure (CPAP) treatment (OSA-T2), 13 untreated OSA patients at 12-month intervals (OSA-NT1, OSA-NT2), and 12 controls (CO1 and CO2) were applied on naïve human microvascular endothelialcells-dermal (HMVEC-d). Expression of several senescence gene markers including p16 (CDKN2A), SIRT1, and SIRT6 and immunostaining for β-galactosidase activity (x-gal) were performed. Endothelial cells were also exposed to intermittent hypoxia (IH) or normoxia (RA) or treated with hydrogen peroxide (H2O2), stained with x-gal and subjected to qRT-PCR. Exosomes from OSA-T1, OSA-NT1, and OSA-NT2 induced significant increases in x-gal staining compared to OSA-T2, CO1, and CO2 (p-value < 0.01). p16 expression was significantly increased (p < 0.01), while SIRT1 and SIRT6 expression levels were decreased (p < 0.02 and p < 0.009). Endothelial cells exposed to IH or to H2O2 showed significant increases in x-gal staining (p < 0.001) and in senescence gene expression. Circulating exosomes in untreated OSA induce marked and significant increases in senescence of naïve endothelial cells, which are only partially reversible upon long-term adherent CPAP treatment. Furthermore, endothelial cells exposed to IH or H2O2 also elicit similar responses. Thus, OSA either directly or indirectly via exosomes may initiate and exacerbate cellular aging, possibly via oxidative stress-related pathways.
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Project description:INTRODUCTION:Little is known about the impact of spousal involvement on continuous positive airway pressure (CPAP) adherence. The aim of this study was to determine whether spouse involvement affects adherence with CPAP therapy, and how this association varies with gender. METHODS:194 subjects recruited from Apnea Positive Pressure Long Term Efficacy Study (APPLES) completed the Dyadic Adjustment Scale (DAS). The majority of participants were Caucasian (83%), and males (73%), with mean age of 56 years, mean BMI of 31 kg/m2. & 62% had severe OSA. The DAS is a validated 32-item self-report instrument measuring dyadic consensus, satisfaction, cohesion, and affectional expression. A high score in the DAS is indicative of a person's adjustment to the marriage. Additionally, questions related to spouse involvement with general health and CPAP use were asked. CPAP use was downloaded from the device and self-report, and compliance was defined as usage ? 4 h per night. RESULTS:There were no significant differences in overall marital quality between the compliant and noncompliant subjects. However, level of spousal involvement was associated with increased CPAP adherence at 6 months (p=0.01). After stratifying for gender these results were significant only among males (p=0.03). Three years after completing APPLES, level of spousal involvement was not associated with CPAP compliance even after gender stratification. CONCLUSION:Spousal involvement is important in determining CPAP compliance in males in the 1st 6 months after initiation of therapy but is not predictive of longer-term adherence. Involvement of the spouse should be considered an integral part of CPAP initiation procedures. SUPPORT:HL068060.
| S-EPMC5512877 | biostudies-literature
Project description:The treatment of choice for obstructive sleep apnoea (OSA) is continuous positive airway pressure therapy (CPAP). Since its introduction in clinical practice, CPAP has been used in various clinical conditions with variable and heterogeneous outcomes. In addition to the well-known effects on the upper airway CPAP impacts on intrathoracic pressures, haemodynamics and blood pressure (BP) control. However, short- and long-term effects of CPAP therapy depend on multiple variables which include symptoms, underlying condition, pressure used, treatment acceptance, compliance and usage. CPAP can alter long-term cardiovascular risk in patients with cardiorespiratory conditions. Furthermore, the effect of CPAP on the awake patient differs from the effect on the patients while asleep, and this might contribute to discomfort and removal of the use interface. The purpose of this review is to highlight the physiological impact of CPAP on the cardiorespiratory system, including short-term benefits and long-term outcomes.
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Project description:BACKGROUND:Obstructive sleep apnea (OSA) is common in acute coronary syndrome (ACS) and a possible cause of increased morbidity and mortality. OBJECTIVES:The main objective is to determine in patients with ACS and OSA if CPAP treatment reduces the incidence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and hospitalization for unstable angina or transient ischemic attack). The secondary objectives are to determine the prevalence of nonsleepy OSA in patients with ACS; assess the effect of CPAP on the incidence of newly diagnosed diabetes mellitus, symptoms, and quality of life; identify biomarkers of risk involved in cardiovascular complications in these patients; and conduct a cost-effectiveness analysis of diagnosis and treatment. POPULATION AND METHODOLOGY:Multicenter, prospective, randomized and controlled study. Patients are admitted to the coronary care unit with diagnosis of ACS and without daytime sleepiness (Epworth Sleepiness Scale ?10) at 15 teaching hospitals in Spain. All patients undergo a sleep study by cardiorespiratory polygraphy. Patients with an apnea-hypopnea index ?15/hour will be randomized to treatment with CPAP (group 1, 632 patients) or conservative treatment (group 2, 632 patients). Patients with an apnea-hypopnea index <15/hour (group 3, 600 patients) will be followed as a reference group. Patients will be monitored at baseline (T0), 1 month (T1), 3 months (T2), 6 months (T3), 12 months (T4), and every 6 months thereafter (where applicable) during the follow-up period. CONCLUSIONS:The ISAACC trial will contribute to evaluating the effect of CPAP treatment on cardiovascular events in patients with ACS and OSA.
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Project description:Study objectivesOral appliance therapy has emerged as an important alternative to continuous positive airway pressure (CPAP) in treating patients with obstructive sleep apnea syndrome (OSAS). In this study we report about the subjective and objective treatment outcome of oral appliance therapy and CPAP in patients with OSAS.DesignCohort study of a previously conducted randomized clinical trial.SettingUniversity Medical Center, Groningen, The Netherlands.Patients or participantsOne hundred three patients with OSAS.InterventionsCPAP and oral appliance therapy (Thornton Adjustable Positioner type-1, Airway Management, Inc., Dallas, TX, USA).Measurements and resultsObjective (polysomnography) and subjective (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Medical Outcomes Study 36-item Short Form Health Survey [SF-36]) parameters were assessed after 1 and 2 years of treatment. Treatment was considered successful when the apnea-hypopnea index (AHI) was < 5 or showed substantial reduction, defined as reduction in the index of at least 50% from the baseline value to a value of < 20 in a patient without OSAS symptoms while undergoing therapy. Regarding the proportions of successful treatments, no significant difference was found between oral appliance therapy and CPAP in treating mild to severe OSAS in a 2-year follow-up. More patients (not significant) dropped out under oral appliance therapy (47%) compared with CPAP (33%). Both therapies showed substantial improvements in polysomnographic and neurobehavioral outcomes. However, CPAP was more effective in lowering the AHI and showed higher oxyhemoglobin saturation levels compared to oral appliance therapy (P < 0.05).ConclusionsOral appliance therapy should be considered as a viable treatment alternative to continuous positive airway pressure (CPAP) in patients with mild to moderate obstructive sleep apnea syndrome (OSAS). In patients with severe OSAS, CPAP remains the treatment of first choice.Clinical trial informationThe original randomized clinical trial, of which this study is a 2-year follow-up, is registered at ISRCTN.org; identifier: ISRCTN18174167; trial name: Management of the obstructive sleep apnea-hypopnea syndrome: oral appliance versus continuous positive airway pressure therapy; URL: http://www.controlled-trials.com/ISRCTN18174167.
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Project description:PURPOSE:To determine if a real-time magnetic resonance imaging (RT-MRI) method during continuous positive airway pressure (CPAP) can be used to measure neuromuscular reflex and/or passive collapsibility of the upper airway in individual obstructive sleep apnea (OSA) subjects. MATERIALS AND METHODS:We conducted experiments on four adolescents with OSA and three healthy controls, during natural sleep and during wakefulness. Data were acquired on a clinical 3T scanner using simultaneous multislice (SMS) RT-MRI during CPAP. CPAP pressure level was alternated between therapeutic and subtherapeutic levels. Segmented airway area changes in response to rapid CPAP pressure drop and restoration were used to estimate 1) upper airway loop gain (UALG), and 2) anatomical risk factors, including fluctuation of airway area (FAA). RESULTS:FAA significantly differed between OSA patients (2-4× larger) and healthy controls (Student's t-test, P < 0.05). UALG and FAA measurements indicate that neuromuscular reflex and passive collapsibility varied among the OSA patients, suggesting the presence of different OSA phenotypes. Measurements had high intrasubject reproducibility (intraclass correlation coefficient r > 0.7). CONCLUSION:SMS RT-MRI during CPAP can reproducibly identify physiological traits and anatomical risk factors that are valuable in the assessment of OSA. This technique can potentially locate the most collapsible airway sites. Both UALG and FAA possess large variation among OSA patients. LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1400-1408.
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