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.

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.

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.

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.

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.

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.

Differential blood pressure response to continuous positive airway pressure treatment according to the circadian pattern in hypertensive patients with obstructive sleep apnoea.

Continuous positive airway pressure (CPAP) has a heterogeneous effect on blood pressure (BP) in hypertensive patients. However, the effect of CPAP on BP in hypertensive subjects regarding circadian BP pattern has never been explored. This study aimed to assess the effect of CPAP on BP, taking into consideration the circadian BP pattern in untreated hypertensive patients.This study is a post hoc analysis of the Spanish Cohort for the Study of the Effect of CPAP in Hypertension (CEPECTA), a multicentre, randomised trial of CPAP versus sham-CPAP in patients with new-onset systemic hypertension and an apnoea-hypopnoea index >15 events·h-1 We included patients for whom 24-h ambulatory BP monitoring (ABPM) data were available at baseline and 12 weeks after the intervention. Subjects were classified based on the dipping ratio (dipper/non-dipper). We evaluated the effect of CPAP on ABPM parameters after 12 weeks of treatment.Overall, 272 hypertensive subjects were included in the analysis (113 dippers and 159 non-dippers). Baseline clinical and polysomnographic variables were similar between the groups. CPAP treatment in non-dipper patients was associated with reductions in 24-h ambulatory BP variables and night-time ambulatory BP measurements. However, a nonsignificant effect was reported in the dipper group. The differential effects of CPAP between the groups were -2.99 mmHg (95% CI -5.92-- -0.06 mmHg) for the mean 24-h ambulatory BP and -5.35 mmHg (95% CI -9.01- -1.69 mmHg) for the mean night-time ambulatory BP.Our results show a differential effect of CPAP treatment on BP in hypertensive patients depending on the circadian pattern. Only non-dipper patients benefited from CPAP treatment in terms of BP reduction.

Soluble PD-L1 is a potential biomarker of cutaneous melanoma aggressiveness and metastasis in obstructive sleep apnoea patients.

Obstructive sleep apnoea (OSA) upregulates the programmed cell death-1 receptor and its ligand (PD-L1) pathway, potentially compromising immunosurveillance. We compared circulating levels of soluble PD-L1 (sPD-L1) in patients with cutaneous melanoma according to the presence and severity of OSA, and evaluated relationships with tumour aggressiveness and invasiveness.In a multicentre observational study, 360 patients with cutaneous melanoma underwent sleep studies, and serum sPD-L1 levels were assayed using ELISA. Cutaneous melanoma aggressiveness indices included mitotic rate, Breslow index, tumour ulceration, Clark level and tumour stage, and sentinel lymph node (SLN) metastasis was recorded as a marker of invasiveness.sPD-L1 levels were higher in severe OSA compared to mild OSA or non-OSA patients. In OSA patients, sPD-L1 levels correlated with Breslow index and were higher in patients with tumour ulceration, advanced primary tumour stages or with locoregional disease. The incorporation of sPD-L1 to the classic risk factors to SLN metastasis led to net improvements in the classification of 27.3%.Thus, sPD-L1 levels are increased in melanoma patients with severe OSA, and, in addition, might serve as a potential biomarker of cutaneous melanoma aggressiveness and invasiveness in this group of subjects.

Management of obstructive sleep apnoea in a primary care vs sleep unit setting: a randomised controlled trial.

OBJECTIVE: To assess the effectiveness and cost-effectiveness of primary care (PC) and sleep unit (SU) models for the management of subjects with suspected obstructive sleep apnoea (OSA). METHODS: Multicentre, open-label, two-arm, parallel-group, non-inferiority randomised controlled trial. A total of 302 subjects with suspected OSA and/or resistant hypertension were consecutively enrolled, 149 were treated at 11 PC units and 153 patients at a SU. The primary outcomes were a 6-month change in the Epworth Sleepiness Scale (ESS) score and Health Utilities Index (HUI). The non-inferiority margin for the ESS score was -2.0. RESULTS: A total of 80.2% and 70.6% of the PC and SU patients were diagnosed with OSA, respectively, and 59.3% and 60.4% of those were treated with CPAP in PC and SU units, respectively. The Apnoea-Hypopnoea Index was similar between the groups (PC vs SU (median (IQR); 23.1 (26.8) events/h vs 21.8 (35.2) events/h), and the baseline ESS score was higher in the PC than in the SU group (10.3 (6.6) vs 9 (7.2)). After 6 months, the ESS score of the PC group decreased from a mean of 10.1 to 7.6 (-2.49; 95% CI -3.3 to -1.69), and that of the SU group decreased from 8.85 to 5.73 (-3.11; 95% CI -3.94 to 2.28). The adjusted difference between groups for the mean change in the ESS score was -1.25 (one-sided 95% CI -1.88; p=0.025), supporting the non-inferiority of PC management. We did not observe differences in the HUI between groups. The cost analysis showed a median savings of €558.14/patient for the PC setting compared with the SU setting. CONCLUSIONS: Among patients with suspected OSA, the PC model did not result in a worse ESS score or HUI than the specialist model and generated savings in terms of management cost. Therefore, the PC model was more cost-efficient than the SU model. TRIAL REGISTRATION: Results; >>NCT02234765, Clinical Trials.gov.