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Cardiovascular morbidities of obstructive sleep apnea and the role of circulating extracellular vesicles.

ABSTRACT: Obstructive sleep apnea (OSA) is characterized by recurrent upper airway collapse during sleep resulting in impaired blood gas exchange, namely intermittent hypoxia (IH) and hypercapnia, fragmented sleep (SF), increased oxidative stress and systemic inflammation. Among a myriad of potential associated morbidities, OSA has been particularly implicated as mechanistically contributing to the prevalence and severity of cardiovascular diseases (CVD). However, the benefits of continuous positive airway pressure (CPAP), which is generally employed in OSA treatment, to either prevent or improve CVD outcomes remain unconvincing, suggesting that the pathophysiological mechanisms underlying the incremental CVD risk associated with OSA are not clearly understood. One of the challenges in development of non-invasive diagnostic assays is the ability to identify clinically and mechanistically relevant biomarkers. Circulating extracellular vesicles (EVs) and their cargos reflect underlying changes in cellular homeostasis and can provide insights into how cells and systems cope with physiological perturbations by virtue of the identity and abundance of miRNAs, mRNAs, proteins, and lipids that are packaged in the EVs under normal as well as diseased states, such as OSA. EVs can not only provide unique insights into coordinated cellular responses at the organ or systemic level, but can also serve as reporters of the effects of OSA in CVD, either by their properties enabling regeneration and repair of injured vascular cells or by damaging them. Here, we highlight recent progress in the pathological CVD consequences of OSA, and explore the putative roles of EVs in OSA-associated CVD, along with emerging diagnostic and therapeutic opportunities. The reviews of this paper are available via the supplemental material section.

SUBMITTER: Khalyfa A

PROVIDER: S-EPMC6923690 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Cardiovascular morbidities of obstructive sleep apnea and the role of circulating extracellular vesicles.

Khalyfa Abdelnaby A Castro-Grattoni Anabel L AL Gozal David D

Therapeutic advances in respiratory disease 20190101

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway collapse during sleep resulting in impaired blood gas exchange, namely intermittent hypoxia (IH) and hypercapnia, fragmented sleep (SF), increased oxidative stress and systemic inflammation. Among a myriad of potential associated morbidities, OSA has been particularly implicated as mechanistically contributing to the prevalence and severity of cardiovascular diseases (CVD). However, the benefits of continuous positive airwa ...[more]

PMID: 31852426

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Project description:Study objectivesUncertainty exists over whether continuous positive airway pressure (CPAP) treatment improves moderate to vigorous physical activity levels in those with obstructive sleep apnea. We aimed to determine effects of CPAP on moderate to vigorous physical activity among participants with co-occurring cardiovascular disease and obstructive sleep apnea.MethodsThe Sleep Apnea cardioVascular Endpoints (SAVE) trial recruited participants with confirmed cardiovascular disease history and obstructive sleep apnea, 45-75 years old. The 2,687 participants (1,346 randomized to CPAP plus usual care and 1,341 to usual care alone) were followed up for a mean of 3.7 years. Self-reported physical activity was recorded at baseline, 6, 24, and 48 months using the Godin-Shepard Leisure Time Exercise Questionnaire (LTEQ). We also determined effects on any limitation of physical activity reported on the physical functioning subscale of the 36-item short form questionnaire (SF-36) and proportions of participants reaching guideline recommended physical activity levels.ResultsAmong 2,601 participants with available data, those in the CPAP group reported significantly more physical activity compared to the usual care group, with approximately 20% higher reported moderate activities on the LTEQ during follow-up (adjusted mean 95% confidence interval) scores: 8.7, 7.5-9.9 vs 7.3, 6.1-8.5; P = .003). Those in the CPAP group also reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score 1.66, 95% confidence interval 0.87-2.45; P < 0.001), and more reported sufficient levels of physical activity to meet recommendations.ConclusionsCPAP has positive effects on improving physical activity levels, consistent with long-term health benefits.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease (SAVE); URL: https://clinicaltrials.gov/ct2/show/NCT00738179; Identifier: NCT00738179; and Registry: Australian New Zealand Clinical Trials Registry; Name: Sleep Apnea cardioVascular Endpoints study-An investigation of continuous positive airway pressure for the treatment of obstructive sleep apnea to prevent cardiovascular disease; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83062&isReview=true; Identifier: ACTRN12608000409370.

Project description:Rationale: Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular consequences.Objectives: To characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study.Methods: Data from 1,207 patients with OSA (apnea-hypopnea index ≥ 15 events/h) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease and its components (coronary heart disease, heart failure, and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality.Measurements and Main Results: Four symptom subtypes were identified (disturbed sleep [12.2%], minimally symptomatic [32.6%], excessively sleepy [16.7%], and moderately sleepy [38.5%]), similar to prior studies. In adjusted models, although no significant associations with prevalent cardiovascular disease were found, the excessively sleepy subtype was associated with more than threefold increased risk of prevalent heart failure compared with each of the other subtypes. Symptom subtype was also associated with incident cardiovascular disease (P < 0.001), coronary heart disease (P = 0.015), and heart failure (P = 0.018), with the excessively sleepy again demonstrating increased risk (hazard ratios, 1.7-2.4) compared with other subtypes. When compared with individuals without OSA (apnea-hypopnea index < 5), significantly increased risk for prevalent and incident cardiovascular events was observed mostly for patients in the excessively sleepy subtype.Conclusions: OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.

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Cardiovascular morbidities of obstructive sleep apnea and the role of circulating extracellular vesicles.

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Cardiovascular morbidities of obstructive sleep apnea and the role of circulating extracellular vesicles.

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