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Introduction: Among all patients with hypertension, those with resistant hypertension (RH) have the highest rates of subclinical organ damage (SOD). The prevalence of obstructive sleep apnea (OSA) is high in RH patients, and it could contribute to SOD. We aimed to investigate how OSA and its treatment are related to SOD in a large cohort of RH patients., Methods: This is an ancillary analysis to the SARAH study, a multicentre observational cohort aiming to evaluate the impact of OSA on RH. Individuals with RH who were undergoing a sleep study and have information on at least one of the SOD variables (vascular, cardiac or renal damage) were selected. Patients were followed-up for three years., Results: In total, 503 subjects were included. The participants were predominantly male, obese, and the median (IQR) apnea-hypopnea index (AHI) was 15.5 (7.90-31.5)events/h. No differences in the presence of vascular or cardiac damage were observed between OSA and non-OSA patients. A lower estimated glomerular filtration rate (eGFR) was observed in participants with OSA than in those without OSA, with an adjusted effect of -8.69mL/min/1.73m 2 (-13.59, -3.79; p value<0.001). Kidney damage was also greater in subjects with OSA, with an adjusted OR (95% CI) of 1.77 (1.09, 2.87; p value=0.02). The eGFR showed a linear dose-response relationship with OSA severity. Among patients treated with CPAP, lower eGFR values were observed in noncompliant subjects., Conclusions: OSA could contribute to worsening renal function in patients with RH. No compliance with CPAP was associated with lower values of eGFR., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: There is a close relationship between obstructive sleep apnoea (OSA) and resistant hypertension (RH). However, studies assessing the long-term effect of diagnosing and treating OSA on blood pressure (BP) control in these patients are lacking., Methods: To address this gap, we recruited 478 RH patients from hypertension units and followed them prospectively after they were screened for OSA through a sleep study. By performing 24-h ambulatory BP monitoring (ABPM) annually, the effect of OSA management was assessed., Results: The patients had a median (interquartile range (IQR)) age of 64.0 (57.2-69.0) years, 67% were males and most were nonsleepy, with a median (IQR) apnoea-hypopnoea index (AHI) of 15.8 (7.9-30.7) events·h -1 . The median (IQR) follow-up time was 3.01 (2.93-3.12) years. At baseline, severe OSA was associated with uncontrolled BP, nocturnal hypertension and a nondipper circadian BP pattern. Moreover, these patients had higher BP values during follow-up than did patients in the other groups. However, among patients with moderate and severe OSA, the management of sleep disordered breathing, including the implementation of continuous positive airway pressure treatment, was associated with a reduction in 24-h ABPM parameters, especially night-time BP values, at the 1-year follow-up. These benefits were attenuated over time and only subjects with severe OSA maintained an ABPM night-time reduction at 3 years. Furthermore, clinical variables such as uncontrolled BP, sex and age showed a predictive value for the BP response at 1 year of follow-up., Conclusion: A favourable long-term decrease in BP was detected by diagnosing and treating OSA in a cohort of RH patients from hypertension units, but over time this decrease was only partially maintained in severe OSA patients., Competing Interests: Conflict of interest: F. Barbé received research grants from Philips Respironics Inc. and ResMed (companies that develop products related to sleep apnoea), the Health Research Fund, the Spanish Ministry of Health, and the Spanish Respiratory Society to develop the SARAH study. Philips Respironics Inc. and ResMed partly funded the SARAH study but did not participate in nor were they involved in decisions regarding study development or the present manuscript. The remaining authors declare no competing interests., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Importance: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated., Objective: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials., Data Sources: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023., Study Selection: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included., Data Extraction and Synthesis: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597])., Main Outcomes and Measures: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day)., Results: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92])., Conclusions and Relevance: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.

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.)

Rationale: Primary care clinicians may be well placed to play a greater role in obstructive sleep apnea (OSA) management. Objectives: To evaluate the outcomes and cost-effectiveness of sleep apnea management in primary versus specialist care, using an individual-participant data meta-analysis to determine whether age, sex, severity of OSA, and daytime sleepiness impacted outcomes. Methods: Data sources were the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP, Scopus, ProQuest, U.S. National Institutes of Health Ongoing Trials Register, and ISRCTN registry (inception until 09-25-2019). Hand searching was undertaken. Two authors independently assessed articles and included trials that randomized adults with a suspected diagnosis of sleep apnea to primary versus specialist management within the same study and reported daytime sleepiness using the Epworth Sleepiness Scale (range 0-24; >10 indicates pathological sleepiness; minimum clinically important difference 2 units) at baseline and follow-up. Results: The primary analysis combined data from 970 (100%) participants (four trials). Risk of bias was assessed (Cochrane Tool). One-stage intention-to-treat analysis showed a slightly smaller decrease in daytime sleepiness (0.8; 0.2 to 1.4), but greater reduction in diastolic blood pressure in primary care (-1.9; -3.2 to -0.6 mm Hg), with similar findings in the per-protocol analysis. Primary care-based within-trial healthcare system costs per participant were lower (-$448.51 U.S.), and quality-adjusted life years and daytime sleepiness improvements were less expensive. Similar primary outcome results were obtained for subgroups in both management settings. Conclusions: Similar outcomes in primary care at a lower cost provide strong support for implementation of primary care-based management of sleep apnea.

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558)., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The COVID-19 emergency pandemic resulting from infection with SARS-CoV-2 represents a major threat to public health worldwide. There is an urgent clinical demand for easily accessible tools to address weaknesses and gaps in the management of COVID-19 patients. In this context, transcriptomic profiling of liquid biopsies, especially microRNAs (miRNAs), has recently emerged as a robust source of potential clinical indicators for medical decision-making. Nevertheless, the analysis of the circulating miRNA signature and its translation to clinical practice requires strict control of a wide array of methodological details. In this review, we indicate the main methodological aspects that should be addressed when evaluating the circulating miRNA profiles in COVID-19 patients, from preanalytical and analytical variables to the experimental design, impact of confounding, analysis of the data and interpretation of the findings, among others. Additionally, we provide practice points to ensure the rigour and reproducibility of miRNA-based biomarker investigations of this condition. Abbreviations: ACE: angiotensin-converting enzyme; ARDS: acute respiratory distress syndrome; COVID-19: coronavirus disease 2019; ERDN: early Detection Research Network; LMWH: low molecular weight heparin; miRNA: microRNA; ncRNA: noncoding RNA; SARS-CoV-2: severe acute respiratory syndrome coronavirus-2; SOP: standard operating procedure.

Background: Membrane-derived extracellular vesicles (EVs) are released to the circulation by cells found in adipose tissue, transferring microRNAs (miRNAs) that may mediate the adaptive response of recipient cells. This study investigated plasma EVs from obese vs. nonobese women and their functional impact in adipocytes., Methods: Plasma EVs were isolated by differential centrifugation. Concentration and size were examined by nanoparticle tracking analysis (NanoSight). RNA was purified from plasma and plasma EVs of 45 women (47 ± 12 years, 58% of obesity) and profiles of mature miRNAs were assessed. Functional analyses were performed in human adipocytes., Findings: Smaller plasma EVs were found in obese when compared to nonobese women. Positive associations were identified between circulating EVs numbers and parameters of impaired glucose tolerance. Almost 40% of plasma cell-free miRNAs were also found in isolated plasma EVs, defined as Ct values < 37 in ≥75% of samples. BMI together with parameters of insulin resistance were major contributors to EVs-contained miRNA patterns. Treatments of cultured human adipocytes with EVs from obese women led to a significant reduction of genes involved in lipid biosynthesis, while increasing the expression of IRS1 (12.3%, p = 0.002)., Interpretation: Size, concentration and the miRNA cargo of plasma EVs are associated with obesity and parameters of insulin resistance. Plasma EVs may mediate intercellular communication relevant to metabolism in adipocytes., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)