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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.)

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) therapy for cardiovascular disease (CVD) prevention among patients with obstructive sleep apnea (OSA) have been largely neutral. However, given that OSA is a heterogeneous disease, there may be unidentified subgroups demonstrating differential treatment effects. Objectives: We sought to apply a novel data-drive approach to identify nonsleepy OSA subgroups with heterogeneous effects of CPAP on CVD outcomes within the Impact of Sleep Apnea Syndrome in the Evolution of Acute Coronary Syndrome (ISAACC) study. Methods: Participants were randomly partitioned into two datasets. One for training (70%) our machine-learning model and a second (30%) for validation of significant findings. Model-based recursive partitioning was applied to identify subgroups with heterogeneous treatment effects. Survival analysis was conducted to compare treatment (CPAP vs. usual care [UC]) outcomes within subgroups. Results: A total of 1,224 nonsleepy OSA participants were included. Of 55 features entered into our model, only two appeared in the final model (i.e., average OSA event duration and hypercholesterolemia). Among participants at or below the model-derived average event duration threshold (19.5 s), CPAP was protective for a composite of CVD events (training hazard ratio [HR], 0.46; P  = 0.002). For those with longer event duration (>19.5 s), an additional split occurred by hypercholesterolemia status. Among participants with longer event duration and hypercholesterolemia, CPAP resulted in more CVD events compared with UC (training HR, 2.24; P  = 0.011). The point estimate for this harmful signal was also replicated in the testing dataset (HR, 1.83; P  = 0.118). Conclusions: We discovered subgroups of nonsleepy OSA participants within the ISAACC study with heterogeneous effects of CPAP. Among the training dataset, those with longer OSA event duration and hypercholesterolemia had nearly 2.5 times more CVD events with CPAP compared with UC, whereas those with shorter OSA event duration had roughly half the rate of CVD events if randomized to CPAP.

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.)

A non-dipping blood pressure (BP) pattern, which is frequently present in patients with obstructive sleep apnea (OSA), confers high cardiovascular risk. The mechanisms connecting these two conditions remain unclear. In the present study we performed a comprehensive analysis of the blood metabolipidome that aims to provide new insights into the molecular link between OSA and the dysregulation of circadian BP rhythmicity. This was an observational prospective longitudinal study involving adults with suspected OSA who were subjected to full polysomnography (PSG). Patients with an apnea-hypopnea index ≥ 5 events/h were included. Fasting plasma samples were obtained the morning after PSG. Based on the dipping ratio (DR; ratio of night/day BP values) measured via 24 h ambulatory BP monitoring, two groups were established: dippers (DR ≤ 0.9) and non-dippers (DR > 0.9). Treatment recommendations for OSA followed the clinical guidelines. Untargeted metabolomic and lipidomic analyses were performed in plasma samples via liquid chromatography-tandem mass spectrometry. Non-dipper patients represented 53.7% of the cohort (88/164 patients). A set of 31 metabolic species and 13 lipidic species were differentially detected between OSA patients who present a physiologic nocturnal BP decrease and those with abnormal BP dipping. Among the 44 differentially abundant plasma compounds, 25 were putatively identified, notably glycerophospholipids, glycolipids, sterols, and fatty acid derivates. Multivariate analysis defined a specific metabotype of non-dipping BP, which showed a significant dose-response relationship with PSG parameters of OSA severity, and with BP dipping changes after 6 months of OSA treatment with continuous positive airway pressure (CPAP). Bioinformatic analyses revealed that the identified metabolipidomic profile was found to be implicated in multiple systemic biological pathways, with potential physiopathologic implications for the circadian control of BP among individuals with OSA.

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.

Purpose: The determination of the programmed death ligand-1 (PD-L1) expression is part of the diagnostic algorithm for advanced non-small cell lung cancer (NSCLC) patients. We aimed to analyze the diagnostic performance of EBUS-TBNA performed as first-choice nodal staging procedure for the determination of PD-L1 expression in NSCLC patients., Methods: Longitudinal-prospective study including NSCLC patients diagnosed between January 2018 and October 2019, for whom a primary tumor biopsy sample and an EBUS-TBNA cytological malignant sample were available. Samples with fewer than 100 malignant cells were considered inadequate. PDL-1 IHC 22C3 pharmDx antibody was used. The percentage of tumor cells expressing PD-L1, setting 1% and 50% as cutoff points, was collected. The weighted kappa coefficient was used to assess the concordance of PD-L1 expression. The PD-L1 expression was compared in precision terms., Results: From a total of 43 patients, 53 pairs of samples were obtained, of which 23 (43.4%) were adequate and included for analysis. The weighted kappa coefficient for PD-L1 expression was 0.41 (95% CI 0.15-0.68) and 0.56 (95% CI 0.23-0.9) for cutoff values ≥ 1% and ≥ 50%, respectively. In advanced stages, the weighted kappa coefficient was 0.6 (95% CI 0.3-0.9) and 1 (95% CI 1-1) for PD-L1 expression cutoff values ≥ 1% and ≥ 50%, respectively. EBUS-TBNA showed a sensitivity, specificity, positive predictive value, and negative predictive value of 1 to detect PDL-1 expression ≥ 50% in advanced stages., Conclusion: EBUS-TBNA performed as first nodal staging procedure in advanced NSCLC patients provides reliable specimens for the detection of PD-L1 expression ≥ 50% and could guide immunotherapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus ( N  = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N  = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) ( N  = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or <15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P  = 0.031; and 2.35 [1.12-4.93], P  = 0.024) and in the PLSC (1.36 [1.13-1.63], P  = 0.001; and 1.44 [1.06-1.94], P  = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P  = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P  = 0.031; and HR, 0.91 [0.86-0.96], P  < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

We characterized the polysomnography (PSG) parameters associated with alterations in the circadian blood pressure (BP) pattern aiming to identify the main contributors to explain the nondipper profile in obstructive sleep apnea (OSA). This is an observational prospective-multicenter study that included participants referred to the sleep unit for suspected OSA. Following a PSG study, subjects with an apnea-hypopnea index (AHI) ≥5 events/hr were included. Two groups were established based on the 24-hr ambulatory blood pressure monitoring dipping ratio (DR; night/day BP ratio): dippers (DR ≤ 0.9) and nondippers (DR > 0.9). The cohort consisted of 299 patients: 131 (43.8%) dippers and 168 (56.2%) nondippers. A significant increase in the risk of presenting a nondipper BP pattern was found along with AHI gain [odds ratio (OR) (95% CI) = 1.71 (1.28 to 2.28)]. The best AHI cutoff for predicting nondipper status was 25.2 events/hr, increasing the OR (95% CI) to 3.50 (2.02 to 6.07). The hypopnea index [OR (95% CI) = 1.70 (1.27 to 2.26)], TSat90 [OR (95% CI) = 1.41 (1.06 to 1.87)], and respiratory arousal index [OR (95% CI) = 1.74 (1.30 to 2.34)] were individually associated with the risk of a nondipping pattern. Multivariate variable selection processes identified the respiratory arousal index as the most relevant risk factor for the nondipper profile, beyond classical clinical risk factors and usual PSG metrics., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

Breast and prostate cancers have been associated with circadian disruption. Some previous studies examined associations of sleep duration and breast or prostate cancer risk though findings remain inconsistent. This study examines associations of a range of detailed sleep characteristics and breast and prostate cancer risk in a large-scale population-based case-control study, MCC-Spain. A total of 1738 incident breast cancer cases, 1112 prostate cancer cases and frequency matched controls (n = 1910, and 1493 respectively) were recruited. Detailed data on habitual sleep duration, quality, timing, and daytime napping ("siesta") were collected at recruitment. Additional data on sleep habits during both the previous year and at age 40 years were also subsequently captured. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated. There were no associations of habitual sleep duration (h), timing of sleep, or any or specific sleep problems, and either breast and prostate cancer risk. There was a significant positive association of ever taking habitual siestas at recruitment and breast cancer risk (OR = 1.22, 95% CI 1.06-1.42), which strengthened with increased frequency or duration. There were also significant positive associations observed for both breast and prostate cancer, among those reporting recent sleep problems, but not sleep problems at age 40 years, in a subsequent circadian questionnaire. Adverse associations with siesta and disturbed sleep during the previous year likely reflect symptoms of developing/diagnosed cancer and comorbidities. Overall, there was no clear association between various sleep characteristics and breast or prostate cancer risk observed., (© 2022. The Author(s).)

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).

Background: Treatment of chronic hypercapnic failure in COPD patients with home noninvasive ventilation (HNIV) remains unclear., Aim: To create a curated cohort of all COPD patients on HNIV in Catalonia, perform a cluster analysis, and evaluate mortality evolution., Study Design and Methods: This study was a multicenter, observational study including all COPD patients on HNIV on 1st January of 2018. Patients were selected through the Catalan Health Service, and administrative and clinical data were obtained in the previous four years. Principal component analysis of mixed data and hierarchical clustering were performed to identify clusters of patients. Mortality was evaluated from 1 January 2018 until 31 December 2020., Results: A total of 247 patients were enrolled. They were mostly male (78.1%), with a median (SD) age of 70.4 (9.4) years old. In 60%, 55% and 29% of patients, obesity, sleep apnea and heart failure coexisted, respectively. Cluster analysis identified four well-differentiated groups labeled for their clinical characteristics: (1) obese smokers, (2) very severe COPD, (3) sleep apnea and (4) older comorbid males. Patients belonging to Clusters (2) and (4) had a worse prognosis than patients in Clusters (1) and (3)., Interpretation: A high heterogeneity in the prescription of HNIV was demonstrated. Cluster analysis identifies four different groups, of which only one had COPD as the main cause of ventilation, while the other three clusters showed a predominance of other comorbidities. This leads to different survival outcomes, including an overlapping phenotype of obesity-related disease and sleep apnea with better survival., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

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.)

Introduction: Classic cardiovascular risk factors do not explain all the cardiovascular events. Obstructive sleep apnoea (OSA) has been proposed as a potential and prevalent cardiovascular risk factor. Our study aimed to describe the prevalence of OSA in a middle-aged cohort with mild-moderate cardiovascular risk and evaluate its association with atherosclerotic disease., Methods: This is an observational cross-sectional ancillary study of the ILERVAS project which was aimed to study subclinical arterial disease in a cohort with mild-moderate cardiovascular risk. In a sample of consecutive subjects, we performed a sleep study and evaluate OSA prevalence and its association with carotid and femoral atheroma plaques and atherosclerotic burden., Results: Overall, 966 subjects with a median age of 57 years (25-75th percentile; 52-62) and a body mass index (BMI) of 28.5kg/m 2 (25.6-31.6) were included. Of these, 72.6% (69.7%-75.3%) had OSA (apnoea-hypopnoea index (AHI)≥5/h); 35.7% (32.8%-38.8%) had mild OSA (AHI 5-14.9/h) and 36.9% (33.9%-39.9%) had moderate/severe OSA (AHI≥15/h). Mean oxygen saturation and the percentage of time with oxygen saturation<90% (CT90) were associated with atherosclerotic burden (e β (95%CI) 0.932 (0.892, 0.974); 1.005 (1.002, 1.009), respectively) and total plaque (OR (95%CI) 0.88 (0.797,0.971); 1.013 (1.004,1.021), respectively). No association with the AHI or oxygen desaturation index was found., Conclusions: This study confirms a high prevalence of OSA in patients with mild-moderate cardiovascular risk and shows an association between atherosclerotic burden, total and femoral plaque with CT90 and mean oxygen saturation, suggesting the importance of OSA-related hypoxaemia in the induction of atherosclerotic disease., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water associated with colorectal cancer risk but mechanisms are not well understood., Objectives: We explored the association between exposure to THMs and nitrate in drinking water and inflammation markers, and the link with colorectal cancer risk., Methods: A subset of 198 colorectal cancer cases and 205 controls from the multicase-control study MCC-Spain were included. Average concentration of THMs (chloroform, bromodichloromethane, dibromochloromethane, bromoform) and nitrate in tap water at the residence was estimated from age 18 until 2 years before the interview ("long term") and for a recent period (3 years before diagnosis). Serum levels of EGF, eotaxin, G-CSF, IL-17E, IL-1rA, IL-8, IP-10, MDC, MPO, periostin, VEGF, and C-reactive protein (CRP) were measured. We estimated the linear association between inflammation markers and exposure among controls, and the odds ratio of colorectal cancer associated with THM and nitrate exposure, and inflammation markers. A mediation analysis was conducted to identify inflammation markers in the pathway between THM/nitrate exposure and colorectal cancer., Results: Serum concentrations of EGF, IL-8, IL-17E and eotaxin increased with recent residential levels of brominated THMs, chloroforom and/or total THM. No associations were observed for nitrate and for long-term residential THM levels. All residential exposures except chloroform were positively associated with colorectal cancer. Serum concentrations of VEGF and periostin were positively associated with colorectal cancer, while EGF was inversely associated. One protein-exposure combination (periostin-recent ingested brominated THMs) slightly mediated the association with colorectal cancer risk., Discussion: Results suggest that estimated THM exposure is involved in inflammation processes. However, the study design was limited to stablish etiologically relevant associations between the protein levels and colorectal cancer risk. The lack of association between nitrate exposure and inflammation markers suggests other biological mechanisms are involved in the link with colorectal cancer., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10-24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010-2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects' personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08-1.73)) for postnatal average residential THMs higher than 66 μg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91-3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)