Long-term effect of obstructive sleep apnoea management on blood pressure in patients with resistant hypertension: the SARAH study.

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.

The Hypoxic Burden, Clinical Implication of a New Biomarker in the Cardiovascular Management of Sleep Apnea Patients: A Systematic Review.

Background: Obstructive sleep apnea (OSA) is a highly prevalent sleep-disordered breathing. It is associated with adverse co-morbidities, being the most scientific evidence of cardiovascular (CV) disease. Currently, OSA is measured through the apnea-hypopnea index (AHI), the total number of respiratory events per hour of sleep. However, different studies have questioned its utility in OSA management, highlighting the need to search for new parameters that better reflect the heterogeneity of the disease. Hypoxic burden (HB) has emerged as a novel biomarker that informs about the frequency, duration and depth of the desaturation related to the respiratory events. We conducted a systematic review in order to find publications about the heterogeneity of OSA measured by HB and its associations with future disease. Methods: Systematic review was conducted using PubMed and Web of Science. The terms "sleep apne" and "hypoxic burden" were used to look for publications from the date of inception to August 15, 2023. Inclusion criteria: articles in English published in peer-reviewed journals. Exclusion criteria: (1) not available publications; (2) duplicated articles; (3) letters, editorials, and congress communications; (4) articles not including information about HB as a specific biomarker of OSA. Results: 33 studies were included. The results were classified in 2 main sections: (1) HB implication in the CV sphere: HB showed to be a better predictor of CV risk in OSA patients than traditional measures such as AHI with possible clinical management implication in OSA. (2) HB response to OSA treatment: pharmacological and nonpharmacological treatments have demonstrated to be effective in improving hypoxia measured through the HB. Conclusions: HB could be a better and more effective parameter than traditional measurements in terms of diagnosis, risk prediction and therapeutic decisions in patients with OSA. This measure could be incorporated in sleep units and could play a role in OSA management, driving the clinic to a more personalized medicine.

Predictors and markers of the cardiovascular impact of obstructive sleep apnoea.

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is the most common form of sleep-disordered breathing and has been linked to cardiovascular health. However, some of the findings supporting this are controversial. These discrepancies might be a result of heterogeneity among OSA patients, and thus, additional information would be required to better stratify OSA patients according to cardiovascular risk. In this review, we aim to discuss the potential of biomarkers to fulfil this role. RECENT FINDINGS: Randomized controlled trials have been unable to confirm whether OSA treatment with continuous positive airway pressure (CPAP) has a positive effect on cardiovascular outcomes. Emerging physiology-based metrics of OSA seem to be more suitable for identifying patients at higher risk of cardiovascular disease and predicting the effects of CPAP outcomes on cardiovascular health. Similarly, blood-based molecular markers have gained attention in this context over the last few years. SUMMARY: Accurate cardiovascular risk stratification and appropriate treatment allocation for OSA patients remain challenging. However, significant efforts are being made to develop novel tools to address these important issues.

Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea.

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.

Use of pedicled flaps after oncologic resections in pediatric patients.

The aim of this study is to review the indications of pedicled flaps and analyze the results. A observational retrospective study of under 18-year-old oncology patients who required reconstructive surgery with pedicled flaps between 2011 and 2022 was performed. Demographic and clinical variables, indications, complications, and outcomes were collected. 236 patients were reviewed and 13 met inclusion criteria, eight girls and five boys (mean age: 10.6 years). Indications were Ewing's sarcoma (5), osteosarcoma (5), neuroblastoma, desmoid tumor, and neurofibroma. Preoperative PET-CT, MRI and bone scintigraphy were performed. The flaps were used on costal and extremity reconstruction: latissimus dorsi (5), pectoralis (2), medial gastrocnemius (2), combined latissimus dorsi, trapezius and serratus muscle, biceps femoris, fascio-neuro-cutaneous saphenous and cutaneous advancement-rotation. Two were performed on allograft and eight on prosthesis. All allowed immediate and complete closure. Six patients received intraoperative radiotherapy. One flap infection and two vascular complications were reported, a total necrosis, which required a new flap, and a partial necrosis, treated with a local plasty. Chemotherapy was resumed after 21 days (15-31). Mean follow-up time was 5.34 years. Flaps are an effective therapeutic option allowing reconstruction of large defects after pediatric oncologic surgeries. The most frequent complication was vascular.

Hypoxic burden to guide CPAP treatment allocation in patients with obstructive sleep apnoea: a post hoc study of the ISAACC trial.

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.

Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation.

BACKGROUND: In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-ß signalling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed. METHODS: In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-ß were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions. RESULTS: PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-ß expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics. CONCLUSION: In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

Aquatic therapy improves self-reported sleep quality in fibromyalgia patients: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effectiveness of aquatic therapy on pain, sleep quality, psychological symptoms, quality of life, and health status in people diagnosed with fibromyalgia. METHODS: We searched PubMed, CINAHL, The Cochrane Library, PEDro and Scopus databases. Articles were eligible if they were randomised controlled trials (RCTs) analysing the effects of aquatic therapy in adult people diagnosed with fibromyalgia, and published by October of 2022 in English or Spanish. The Cochrane Risk of Bias tool was employed to conduct the methodological quality assessment of the encompassed studies, and the overall quality of evidence for each comparison was determined using the GRADE approach. RESULTS: Of 375 articles found, 22 met the inclusion criteria. Forest plot analysis of Pittsburgh sleep quality index at short- and mid-term follow-up showed a trend in favour of aquatic therapy, although not statistically significant, with weighted mean difference (WMD) = -1.71 (95% CI: -4.17 to -0.75, p = 0.17). Heterogeneity was substantial (χ2 = 8.74, df = 5 (p < 0.000001; I2 = 95%). Relating the pain outcome by fibromyalgia impact questionnaire (FIQ) short term showed a trend in favour of the aquatic therapy group with WMD = -5.04 (95% CI: - 9.26 to - 0.82, p =  = 0.02) with heterogeneity χ2 = 11.07, df = 4 (p = 0.03; I2 = 64%). Great heterogeneity was found between trials in medium term. CONCLUSION: This systematic review and meta-analysis demonstrated the effectiveness of aquatic therapy as an adjunct treatment to usual care in people suffering from fibromyalgia. Aquatic therapeutic exercise improves the symptomats of sleep quality, pain, and quality of life of adults with fibromyalgia. Further research on long-term outcomes may contribute to the currently available evidence.

Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.

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.

Analysis of the Ischemia-Modified Albumin as a Potential Biomarker for Cardiovascular Damage in Obstructive Sleep Apnea Patients with Acute Coronary Syndrome.

Obstructive sleep apnea (OSA) has been identified as a cardiovascular (CV) risk factor. The potential of OSA promoting the synthesis of CV biomarkers in acute coronary syndrome (ACS) is unknown. Ischemia-modified albumin (IMA) has been identified as a specific CV biomarker. The aim of this study was to evaluate the role of IMA as a potential biomarker for determining the impact of OSA in ACS patients. A total of 925 patients (15.5% women, age: 59 years, body mass index: 28.8 kg/m2) from the ISAACC study (NCT01335087) were included. During hospitalization for ACS, a sleep study for OSA diagnosis was performed and blood samples extraction for IMA determination were obtained. IMA values were significantly higher in severe OSA (median (IQR), 33.7 (17.2-60.3) U/L) and moderate (32.8 (16.9-58.8) U/L) than in mild/no OSA (27.7 (11.8-48.6) U/L) (p = 0.002). IMA levels were very weakly related to apnea-hypopnea index (AHI) as well as hospital and intensive care unit stay, although they only maintained a significant relationship with days of hospital stay after adjusting for sex, age and BMI (ß = 0.410, p = 0.013). The results of the present study would suggest a potentially weaker role of OSA in the synthesis of the CV risk biomarker IMA in patients with ACS than in primary prevention.

Micro-RNA in obstructive sleep apnoea: biomarker of cardiovascular outcome?

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is a global health problem with important cardiovascular consequences. Risk assessment tools are essential in OSA to identify patients at increased risk of cardiovascular disease and to achieve a cost-effective clinical management of the disease in the era of precision medicine. The objective is to provide an updated perspective on the role of microRNAs (miRNAs) in OSA as a biomarker of cardiovascular risk. RECENT FINDINGS: Specific miRNAs have already been associated with patients with OSA and specific cardiovascular diseases such as hypertension, myocardial infarction or endothelial dysfunction. Numerous studies have addressed the use of miRNAs to identify the cardiovascular risk associated with OSA, both in patients and in animals with in vivo hypoxia models. Thus, these studies identified profiles of differentially expressed miRNAs in patients with OSA. In addition, the in vitro studies suggest that therapies with miRNA inhibitors that could help reduce cardiovascular risk. Therefore, this review highlights the primary approaches of the potential of miRNAs as biomarkers at the prognostic, diagnostic and therapeutic strategy levels. SUMMARY: Given the heterogeneity of OSA and its cardiovascular consequences, miRNAs have emerged as powerful biomarkers that can help improve the clinical management of OSA and its cardiovascular risk.

Immunotherapy in hepatocellular carcinoma.

Hepatocellular carcinoma is a highly prevalent tumor worldwide and when it reaches an advanced stage, few systemic treatments are available to improve the survival of these patients. However, greater knowledge about the tumor microenvironment and the role of the immune system in the control of tumor progression has allowed the development of treatments targeting immune checkpoints, which result in encouraging tumor response rates and prolonged survival. Although most of these treatments are well tolerated, up to 20 % of patients may experience side effects derived from non-specific stimulation of the immune system. In the cirrhotic patient, the early diagnosis and treatment of such adverse events is particularly challenging. Therefore, the ongoing investigation on the use of these new therapies will allow us to better understand the profile of the patients who will benefit most.

Proangiogenic factor midkine is increased in melanoma patients with sleep apnea and induces tumor cell proliferation.

Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM patients, sleep studies and MDK serum level measurements were performed. The effect of MDK on cell proliferation was assessed using HLEC and melanoma cell lines with patient sera under both normoxia and IH. MDK levels were higher in severe OSA compared to mild OSA or non-OSA patients, whereas no differences in VEGF levels emerged. In OSA patients, MDK levels correlated with nocturnal hypoxemia and CM mitotic rate. In vitro, MDK promotes HLEC proliferation under IH conditions. Moreover, cultures of the human melanoma cell line C81-61 with sera from patients with the highest MDK levels promoted tumor cell proliferation, which was attenuated after the addition of MDK antibody. These responses were enhanced by IH exposures. In conclusion, in CM patients, OSA severity is associated with higher MDK levels, which, appear to enhance both the lymphangiogenesis as the intrinsic aggressiveness of CM tumor cells.

Canonical Pathways Associated with Blood Pressure Response to Sleep Apnea Treatment: A Post Hoc Analysis.

BACKGROUND: Several studies have reported an association between microRNAs (miRNAs) and hypertension or cardiovascular disease (CVD). In a previous study performed on a group of 38 patients, we observed a cluster of 3 miRNAs (miR-378a-3p, miR-100-5p, and miR-486-5p) that were functionally associated with the cardiovascular system that predicted a favorable blood pressure (BP) response to continuous positive airway pressure (CPAP) treatment in patients with resistant hypertension (RH) and obstructive sleep apnea (OSA) (HIPARCO score). However, little is known regarding the molecular mechanisms underlying this phenomenon. OBJECTIVES: The aim of the study was to perform a post hoc analysis to investigate the genes, functions, and pathways related to the previously found HIPARCO score miRNAs. METHODS: We performed an enrichment analysis using Ingenuity pathway analysis. The genes potentially associated with the miRNAs were filtered based on their confidence level. Particularly for CVD, only the genes regulated by at least 2 of the miRNAs were studied. RESULTS: We observed that the miRNAs studied regulate 200-249 molecules associated with several functions and diseases, including extracranial solid tumors and abdominal neoplasms, among others. The cardiac hypertrophy and NF-kB signaling pathways were identified as the cardiovascular pathways most influenced by these 3 miRNAs. CONCLUSIONS: The mechanisms by which CPAP treatment decreases the BP in OSA patients with RH could be related to the cardiac hypertrophy and NF-kB signaling pathways. Further investigations will be necessary to confirm these findings, contributing to the elucidation of new therapeutic targets in patients who do not respond to CPAP treatment.

Imaging of bee honey sugar crystals by second-harmonic generation microscopy.

Bee honey is an exceptionally nutritious food with unique chemical and mineral contents. This report introduces the use of the second-harmonic generation (SHG) microscopy for imaging honey sugar crystals' morphology as an alternative for its authentication process. The crystals and their boundaries are clearly observed with SHG compared with bright-field microscopy, where the liquid honey avoids the visualization of a sharp image. Four different honey samples of Mexico's various floral origins and geographical regions are analyzed in our study. These samples are representative of the diversity and valuable quality of bee honey production. The SHG image information is complemented with Raman spectroscopy (RS) analysis, since this optical technique is widely used to validate the bee's honey composition stated by its floral origin. We relate the SHG imaging of honey crystals with the well-defined fructose and glucose peaks measured by RS. Size measurement is introduced using the crystal´s length ratio to differentiate its floral origin. From our observations, we can state that SHG is a promising and suitable technique to provide a sort of optical fingerprint based on the floral origin of bee honey.

The Effect of Sleep Apnea on Cardiovascular Events in Different Acute Coronary Syndrome Phenotypes.

Rationale: Obstructive sleep apnea (OSA) is associated with increased cardiovascular disease (CVD) risk. Conversely, OSA has not been shown to increase recurrent cardiovascular events in patients with acute coronary syndrome (ACS). This lack of homogeneity could suggest that the deleterious effect of OSA and its contribution to CVD could depend on specific patient profiles.Objectives: To evaluate the effect of OSA on cardiovascular risk for patients with different ACS phenotypes.Methods:Post hoc analysis of the ISAACC (Continuous Positive Airway Pressure in Patients with ACS and OSA) study, including 1,701 patients admitted for ACS (NCT01335087). To evaluate the presence of OSA (apnea-hypopnea index ≥ 15 events · h-1), all patients underwent polygraphy. Patients were followed up for a minimum period of 1 year. We performed nonsupervised clustering using latent class analysis to identify subgroups of patients on the basis of 12 clinical factors associated with cardiovascular risk. The effect of OSA on recurrent cardiovascular event risk was evaluated for each phenotype identified.Measurements and Main Results: Two phenotypes were identified: patients without previous heart disease and without previous ACS ("no-previous-CVD" phenotype; 81%) and patients with previous heart disease and previous ACS ("previous-CVD" phenotype; 19%). The median (interquartile range) at follow-up was 2.67 (3.8) years. For the no-previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio (95% confidence interval) of 1.54 (1.06-2.24; P value = 0.02), whereas for the previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio of 0.69 (0.46-1.04; P value = 0.08).Conclusions: For patients with ACS and a specific phenotype, OSA is associated with an increased risk of recurrent cardiovascular events. These patients are mainly characterized by no previous heart disease and admission for a first ACS occurrence.

Understanding the pathophysiological mechanisms of cardiometabolic complications in obstructive sleep apnoea: towards personalised treatment approaches.

In January 2019, a European Respiratory Society research seminar entitled "Targeting the detrimental effects of sleep disturbances and disorders" was held in Dublin, Ireland. It provided the opportunity to critically review the current evidence of pathophysiological responses of sleep disturbances, such as sleep deprivation, sleep fragmentation or circadian misalignment and of abnormalities in physiological gases such as oxygen and carbon dioxide, which occur frequently in respiratory conditions during sleep. A specific emphasis of the seminar was placed on the evaluation of the current state of knowledge of the pathophysiology of cardiovascular and metabolic diseases in obstructive sleep apnoea (OSA). Identification of the detailed mechanisms of these processes is of major importance to the field and this seminar offered an ideal platform to exchange knowledge, and to discuss pitfalls of current models and the design of future collaborative studies. In addition, we debated the limitations of current treatment strategies for cardiometabolic complications in OSA and discussed potentially valuable alternative approaches.

Obstructive sleep apnoea and cognitive decline in mild-to-moderate Alzheimer's disease.

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease.In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography.The mean±sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of -3.36 (95% CI 0.19-0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI -1.26-4.64; p=0.445). No significant differences were found among different OSA severity groups.We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.

Effect of age on the cardiovascular remodelling induced by chronic intermittent hypoxia as a murine model of sleep apnoea.

BACKGROUND AND OBJECTIVE: Chronic intermittent hypoxia (CIH) is a major determinant of the cardiovascular morbidity associated with obstructive sleep apnoea (OSA), and the magnitude of CIH impact may be influenced by ageing. Here, we assessed the role of ageing in the early cardiovascular structural remodelling induced by severe CIH in a murine model of OSA. METHODS: Cardiovascular remodelling was assessed in young (2 months old, n = 20) and aged (18 months old, n = 20) C57BL/6 female mice exposed to CIH (20% O2 for 40 s, 5% O2 for 20 s) or normoxia (room air) for 8 weeks (6 h/day). RESULTS: Early vascular remodelling was observed in young mice exposed to CIH as illustrated by intima-media thickening (mean change: 4.6 ± 2.6 µm; P = 0.02), elastin fibre disorganization (mean change: 9.2 ± 4.5%; P = 0.02) and fragmentation (mean change: 2.5 ± 0.8%; P = 0.03), and collagen (mean change: 3.2 ± 0.6%; P = 0.001) and mucopolysaccharide accumulation (mean change: 2.4 ± 0.8%; P = 0.01). In contrast, vascular remodelling was not apparent in aged mice exposed to CIH. Furthermore, left ventricular perivascular fibrosis (mean change: 0.71 ± 0.1; P < 0.001) and hypertrophy (mean change: 0.17 ± 0.1; P = 0.038) were increased by CIH exposure in young mice, but not in aged mice. Principal component analysis identified similar cardiovascular alterations among the young mice exposed to CIH and both older mouse groups, suggesting that CIH induces premature cardiovascular senescence. CONCLUSION: Cardiovascular remodelling induced by severe CIH is affected by the age at which CIH onset occurs, suggesting that the deleterious cardiovascular effects associated with CIH may be more pronounced in younger populations, and such changes resemble chronological age-related declines in cardiovascular structural integrity.

MicroRNA Profile of Cardiovascular Risk in Patients with Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disease caused by repeated episodes of collapse of the upper airway during sleep and is associated with the development of cardiovascular disease (CVD). However, there is high heterogeneity in the impact of OSA on patients. Until now, the profile of OSA patients at risk of developing CVD has not been defined, including the measurable variables that could be used to predict the CVD risk of a patient with OSA. OBJECTIVE: The aim of this study was to identify the microRNA (mi-RNA) profile associated with CVD in patients with OSA. METHOD: This is an observational, cross-sectional study that included 132 male patients. Three groups were defined as OSA patients, OSA patients with hypertension, and OSA patients who developed a major cardiovascular event. Polysomnography and ambulatory blood pressure measurements were performed. The expression profiling of 188 miRNAs in plasma was performed in 21 subjects (matched by BMI and age) by the TaqMan low density array (TLDA). miRNAs differentially expressed in the different subgroups of patients and miRNAs that correlated with the cardiovascular risk SCORE were selected for validation by RT-qPCR in the 111 remaining patients. RESULTS: From the TLDA analysis, 7 miRNAs were selected for validation. Differential expression was not confirmed in any of the miRNAs. miR-143 was associated with nocturnal systolic blood pressure. miR-107 correlated with 24-h blood pressure parameters and with nocturnal hypertension. miR-486 was associated with the cardiovascular risk SCORE. CONCLUSIONS: The circulating profile of miRNAs does not seem to be different in any of the subgroups of patients with OSA and different cardiovascular risk factors. Nevertheless, miR-107 and miR-143 are associated with specific blood pressure parameters in patients with OSA and miR-486 is associated with the cardiovascular risk SCORE.