Effect of continuous positive airway pressure on atrial remodeling and diastolic dysfunction of patients with obstructive sleep apnea and metabolic syndrome: a randomized study.

OBJECTIVE: The aim of this study was to evaluate the role of obstructive sleep apnea (OSA) treatment on heart remodeling and diastolic dysfunction in patients with metabolic syndrome (MS). METHODS: This study is a prespecified analysis of a randomized placebo-controlled trial that enrolled patients with a recent diagnosis of MS and moderate-to-severe OSA to undergo continuous positive airway pressure (CPAP) or nasal dilators (placebo) for 6 months. Patients were invited to perform a transthoracic echocardiogram by a single investigator blinded to treatment assignment. RESULTS: A total of 99 (79% men; mean [SD], age: 48 [9] years; BMI: 33 [4] kg/m2 ) completed the study. At follow-up, in the placebo group, patients had a significant increase in atrial diameter: from 39.5 (37.0-43.0) mm to 40.5 (39.0-44.8) mm (p = 0.003). CPAP prevented atrial enlargement: from 40.0 (38.0-44.0) to 40.0 (39.0-45.0) mm (p = 0.194). In patients with diastolic dysfunction at baseline, almost half had diastolic dysfunction reversibility with CPAP (in comparison with only two patients in the placebo group, p = 0.039). In the regression analysis, the chance of diastolic dysfunction reversibility by CPAP was 6.8-fold (95% CI: 1.48-50.26, p = 0.025) compared with placebo. CONCLUSIONS: In patients with MS and OSA, 6 months of CPAP therapy prevented atrial remodeling and increased the chance of diastolic dysfunction reversibility.

Mass Spectrometry Multiplexed Detection of SARS-CoV-2.

Testing of large populations for virus infection is now a reality worldwide due to the coronavirus (SARS-CoV-2) pandemic. The demand for SARS-CoV-2 testing using alternatives other than PCR led to the development of mass spectrometry (MS)-based assays. However, MS for SARS-CoV-2 large-scale testing have some downsides, including complex sample preparation and slow data analysis. Here, we describe a high-throughput targeted proteomics method to detect SARS-CoV-2 directly from nasopharyngeal and oropharyngeal swabs. This strategy employs fully automated sample preparation mediated by magnetic particles, followed by detection of SARS-CoV-2 nucleoprotein peptides by turbulent flow chromatography coupled with tandem mass spectrometry.

Effects of CPAP on Metabolic Syndrome in Patients With OSA: A Randomized Trial.

BACKGROUND: OSA is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with CPAP can revert MS. RESEARCH QUESTION: Does OSA treatment with CPAP per se have effects on the MS reversibility and the associated metabolic, adiposity and vascular parameters? STUDY DESIGN AND METHODS: The TREATOSA-MS trial is a randomized placebo-controlled trial that enrolled adult patients with a recent diagnosis of MS and moderate or severe OSA (apnea-hypopnea index [AHI], ≥ 15 events/h) to undergo therapeutic CPAP or nasal dilator strips (placebo group) for 6 months. Before and after each intervention, we measured anthropometric variables, BP, glucose, and lipid profile. To control potential-related mechanisms and consequences, we also measured adiposity biomarkers (leptin and adiponectin), body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic fat), and endothelial function. RESULTS: One hundred patients (79% men; mean age, 48 ± 9 years; BMI, 33 ± 4 kg/m2; AHI, 58 ± 29 events/h) completed the study (n = 50 per group). The mean CPAP adherence was 5.5 ± 1.5 h/night. After 6 months, most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group (18% vs 4%; OR, 5.27; 95% CI, 1.27-35.86; P = .04). In the secondary analysis, CPAP did not promote significant reductions in the individual components of MS, weight, hepatic steatosis, lipid profile, adiponectin, and leptin, but did promote a very modest reduction in visceral fat and improved endothelial function (all analyses were adjusted for baseline values). INTERPRETATION: Despite the higher rate of MS reversibility after CPAP therapy as compared with placebo, most patients retained this diagnosis. The lack of significant or relevant effects on adiposity biomarkers and depots supports the modest role of OSA in modulating MS. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02295202; URL: www. CLINICALTRIALS: gov.

Advances and challenges in pursuing biomarkers for obstructive sleep apnea: Implications for the cardiovascular risk.

Obstructive sleep apnea (OSA) is a common clinical condition associated with increased cardiovascular morbidity and mortality. Recent evidence from clinical studies and animal models suggest that OSA can promote cardiovascular disease by inducing autonomic, hemodynamic, inflammatory and metabolic dysregulation. However, most of the evidence addressing hard endpoints in humans is derived from observational studies. Several challenges have been noted in the pursuit of a comprehensive knowledge base about the impact of OSA including: 1) the precise mechanisms by which OSA causes metabolic and cardiovascular consequences are not clear, which limits our current ability to address potential targets in OSA; 2) several patients with OSA, even with severe forms, present with no or mild daytime symptoms. Beyond the obvious challenges for obtaining good adherence for conventional OSA treatments, there is evidence that symptomatic vs. asymptomatic patients with OSA do not necessarily have the same metabolic and cardiovascular outcomes; and 3) the cardiovascular response to OSA treatment may vary even in those patients with good adherence. In this scenario, there is an obvious need to develop biomarkers in the OSA research area. This review focuses on describing the advances that have occurred so far in exploring potential OSA biomarkers with clear emphasis for the cardiovascular risk. Particular attention will be devoted to discuss molecular biomarkers including the potential role of microRNAs, proteomics and metabolomics. We also discuss the major challenges and perspectives in this growing research field.

Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2 in large clinical sample cohorts.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pressing public health systems around the world, and large population testing is a key step to control this pandemic disease. Here, we develop a high-throughput targeted proteomics assay to detect SARS-CoV-2 nucleoprotein peptides directly from nasopharyngeal and oropharyngeal swabs. A modified magnetic particle-based proteomics approach implemented on a robotic liquid handler enables fully automated preparation of 96 samples within 4 hours. A TFC-MS system allows multiplexed analysis of 4 samples within 10 min, enabling the processing of more than 500 samples per day. We validate this method qualitatively (Tier 3) and quantitatively (Tier 1) using 985 specimens previously analyzed by real-time RT-PCR, and detect up to 84% of the positive cases with up to 97% specificity. The presented strategy has high sample stability and should be considered as an option for SARS-CoV-2 testing in large populations.

Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation.

PURPOSE: Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. METHODS: We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group (n = 6), mild OSA group (n = 12), moderate OSA group (n = 15), and severe OSA group (n = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). RESULTS: The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 (ß = 68.4; EP = 29.8; p = 0.02) and miR-320e (ß = 76.1; EP = 31.3; p = 0.02). CONCLUSION: Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.

Metabolomic and lipidomic profile in men with obstructive sleep apnoea: implications for diagnosis and biomarkers of cardiovascular risk.

The use of metabolomic and lipidomic strategies for selecting potential biomarkers for obstructive sleep apnoea (OSA) has been little explored. We examined adult male patients with OSA (defined by an apnoea-hypopnoea index ≥15 events/hour), as well as age-, gender-, and fat-composition-matched volunteers without OSA. All subjects were subjected to clinical evaluation, sleep questionnaires for detecting the risk of OSA (Berlin and NoSAS score), metabolomic analysis by gas chromatography coupled to mass spectrometry and lipidomic analysis with liquid chromatography followed by detection by MALDI-MS. This study included 37 patients with OSA and 16 controls. From the 6 metabolites and 22 lipids initially selected, those with the best association with OSA were glutamic acid, deoxy sugar and arachidonic acid (metabolites), and glycerophosphoethanolamines, sphingomyelin and lyso-phosphocholines (lipids). For the questionnaires, the NoSAS score performed best with screening for OSA (area under the curve [AUC] = 0.724, p = 0.003). The combination of the NoSAS score with metabolites or lipids resulted in an AUC for detecting OSA of 0.911 and 0.951, respectively. In conclusion, metabolomic and lipidomic strategies suggested potential early biomarkers in OSA that could also be helpful in screening for this sleep disorder beyond traditional questionnaires.