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.

Decrease in sleep quality during COVID-19 outbreak.

PURPOSE: The COVID-19 outbreak witnessed in the first months of 2020 has led to unprecedented changes in society's lifestyles. In the current study, we aimed to investigate the effect of this unexpected context on sleep. METHODS: During the COVID-19 outbreak, we performed an online survey with individuals formerly recruited for validation of the Spanish version of the sleep questionnaire Satisfaction, Alertness, Timing, Efficiency, and Duration (SATED). In the current survey, we asked the participants to complete the previously answered questionnaires including the Pittsburgh Sleep Quality Index (PSQI), a modified version of the Epworth Sleepiness Scale (ESS), and the SATED questionnaire. We also assessed the mood by the Profile of Mood States (POMS) questionnaire. RESULTS: The 71 participants were mostly women (75%) with a mean (± SD) age of 40.7 ± 11.9 years. Comparing the previous PSQI score to that during the COVID-19 outbreak, we observed worsening sleep quality (5.45 ± 3.14 to 6.18 ± 3.03 points, p = 0.035). In parallel, there was an increase in the negative mood (p = 0.002). Accordingly, the decrease in sleep quality was substantially correlated with negative mood (p < 0.001). There were no differences in the ESS or SATED. CONCLUSIONS: The COVID-19 outbreak-associated events correlate with decreased sleep quality in association with an increase in negative mood. Considering the importance of sleep for a healthy life, and in particular for immune function, efforts should be made to improve awareness on this matter and to offer psychological assistance to affected individuals.

Management and Treatment of Patients With Obstructive Sleep Apnea Using an Intelligent Monitoring System Based on Machine Learning Aiming to Improve Continuous Positive Airway Pressure Treatment Compliance: Randomized Controlled Trial.

BACKGROUND: Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA), but treatment compliance is often unsatisfactory. OBJECTIVE: The aim of this study was to assess the effectiveness and cost-effectiveness of an intelligent monitoring system for improving CPAP compliance. METHODS: This is a prospective, open label, parallel, randomized controlled trial including 60 newly diagnosed patients with OSA requiring CPAP (Apnea-Hypopnea Index [AHI] >15) from Lleida, Spain. Participants were randomized (1:1) to standard management or the MiSAOS intelligent monitoring system, involving (1) early compliance detection, thus providing measures of patient's CPAP compliance from the very first days of usage; (2) machine learning-based prediction of midterm future CPAP compliance; and (3) rule-based recommendations for the patient (app) and care team. Clinical and anthropometric variables, daytime sleepiness, and quality of life were recorded at baseline and after 6 months, together with patient's compliance, satisfaction, and health care costs. RESULTS: Randomized patients had a mean age of 57 (SD 11) years, mean AHI of 50 (SD 27), and 13% (8/60) were women. Patients in the intervention arm had a mean (95% CI) of 1.14 (0.04-2.23) hours/day higher adjusted CPAP compliance than controls (P=.047). Patients' satisfaction was excellent in both arms, and up to 88% (15/17) of intervention patients reported willingness to keep using the MiSAOS app in the future. No significant differences were found in costs (control: mean €90.2 (SD 53.14) (US $105.76 [SD 62.31]); intervention: mean €96.2 (SD 62.13) (US $112.70 [SD 72.85]); P=.70; €1=US $1.17 was considered throughout). Overall costs combined with results on compliance demonstrated cost-effectiveness in a bootstrap-based simulation analysis. CONCLUSIONS: A machine learning-based intelligent monitoring system increased daily compliance, reported excellent patient satisfaction similar to that reported in usual care, and did not incur in a substantial increase in costs, thus proving cost-effectiveness. This study supports the implementation of intelligent eHealth frameworks for the management of patients with CPAP-treated OSA and confirms the value of patients' empowerment in the management of chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT03116958; https://clinicaltrials.gov/ct2/show/NCT03116958.

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.

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.

Management of continuous positive airway pressure treatment compliance using telemonitoring in obstructive sleep apnoea.

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnoea (OSA), but treatment compliance is often unsatisfactory. This study investigated the efficacy and cost-effectiveness of telemonitoring for improving CPAP compliance.100 newly diagnosed OSA patients requiring CPAP (apnoea-hypopnoea index >15 events·h-1) were randomised to standard management or a telemonitoring programme that collected daily information about compliance, air leaks and residual respiratory events, and initiated patient contact to resolve issues. Clinical/anthropometric variables, daytime sleepiness and quality of life were recorded at baseline and after 3 months. Patient satisfaction, additional visits/calls, side-effects and total costs were assessed.There were no significant differences between the standard and telemedicine groups in terms of CPAP compliance (4.9±2.2 versus 5.1±2.1 h·night-1), symptoms, clinical variables, quality of life and unwanted effects. Telemedicine was less expensive than standard management (EUR123.65 versus EUR170.97; p=0.022) and was cost-effective (incremental cost-effectiveness ratio EUR17 358.65 per quality-adjusted life-year gained). Overall patient satisfaction was high, but significantly more patients rated satisfaction as high/very high in the standard management versus telemedicine group (96% versus 74%; p=0.034).Telemonitoring did not improve CPAP treatment compliance and was associated with lower patient satisfaction. However, it was more cost-effective than traditional follow-up.

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial.

BACKGROUND: Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. AIM: To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. METHODS: A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. RESULTS: We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. CONCLUSIONS: A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). TRIAL REGISTER NUMBER: NCT01716676.

Polysomnographic characterization of circadian blood pressure patterns in patients with obstructive sleep apnea.

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.

Breathing cessation events that compose the apnea-hypopnea index are distinctively associated with the adverse outcomes in Alzheimer's disease.

BACKGROUND: Previous studies challenge the impact of obstructive sleep apnea (OSA) once patients are diagnosed with Alzheimer's disease (AD). Nevertheless, OSA recognizably disrupts sleep, and relevant associations between sleep, AD pathological markers, and cognition have been demonstrated. We aimed to further explore this, evaluating the associations between each breathing cessation event that compose the apnea-hypopnea index (AHI) and the sleep structure to finally investigate whether this was related to increased levels of AD markers and higher cognitive decline. METHODS: Observational, prospective study, including consecutive patients diagnosed with mild-moderate AD. The participants were submitted to overnight polysomnography followed by a cerebrospinal fluid collection for AD pathological markers levels determination. Neuropsychological assessment was performed at baseline and after 12 months of follow-up. RESULTS: The cohort was composed of 116 patients (55.2% females) with a median [p25;p75] age of 76.0 [72.0;80.0] years and an AHI of 25.9 [15.1;48.5], which was mainly defined by the presence of hypopneas and obstructive apneas. These were distinctively associated with the sleep structure, with obstructive apneas being related to arousals and sleep lightening and hypopneas being related to an increased number of arousals only. Despite having a lower frequency, mixed and central apneas also presented associations with the sleep structure, particularly increasing the time spent in the lighter sleep stages. In relation to AD pathological markers, obstructive and mixed apneas were related to an augment in neurofilament light levels while hypopneas were associated with a higher phosphorylated-tau/amyloid-beta protein ratio. Hypopneas were the most important event for an increased cognitive decline at the 12-month follow-up. CONCLUSIONS: Our findings highlight the importance of a patient-centered approach, with a comprehensive and detailed analysis of the AHI to effectively predict the different outcomes and tailor the appropriate therapeutic strategies.

Endogenous controls and microRNA profile in female patients with obstructive sleep apnea.

Recent studies have evaluated the potential of circulating microRNAs (miRNAs) as valuable biomarkers for characterizing obstructive sleep apnea (OSA) in males. The potential use of miRNAs as clinical indicators in females is unknown. The objective is to identify a set of miRNAs to be used as endogenous controls (ECs) in female patients with OSA. Then, to analyze differences in the miRNA expression profile between patients with and without OSA. This observational, longitudinal study included 85 females with suspected OSA who underwent a polysomnography. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The study population was stratified into 50 OSA patients and 38 non-OSA patients. Exploratory expression profiling of 188 miRNAs consistent and reliable in plasma was performed in a discovery cohort of 21 patients by TaqMan-Low-Density-Array (TLDA). The best ECs were identified by mean centre + standard deviation normalization and concordance correlation restricted normalization. Differentially expressed candidate miRNAs were selected for RT-qPCR validation in a validation cohort of 64 patients. Three circulating miRNAs (miR-30a-5p, miR-93-3p and miR-532-5p) were identified as most stable for use as ECs. Twenty-seven miRNA candidates were identified as potential biomarkers for OSA screening (p value < 0.025) in the TLDA cohort. However, validation cohort showed no differences in the circulating miRNA profile in female patients with and without OSA. We identified a set of ECs in females with OSA that may contribute to result homogeneity in determining circulating miRNAs. Exploratory analysis did not identify a significantly miRNA profile between female patients with and without OSA.

Liraglutide Improves Forced Vital Capacity in Individuals With Type 2 Diabetes: Data From the Randomized Crossover LIRALUNG Study.

To evaluate the effect of liraglutide, a glucagon-like peptide 1 receptor agonist, on pulmonary function and serum levels of surfactant protein D (SP-D) in type 2 diabetes. A double-blind, randomized, crossover, placebo-controlled clinical trial comprising 76 patients with a baseline forced expiratory volume in 1 s <90% of that predicted. Liraglutide was administered for 7 weeks (2 weeks of titration plus 5 weeks at 1.8 mg daily). This short duration was intentional to minimize weight loss as a potential confounding factor. Serum level of SP-D was used as a biomarker of alveolar-capillary barrier integrity. Liraglutide exerted a positive impact on forced vital capacity (FVC) in comparison with placebo (ΔFVC 5.2% of predicted [from 0.8 to 9.6]; P = 0.009). No differences in the other pulmonary variables were observed. Participants under liraglutide treatment also experienced a decrease in serum SP-D (P = 0.038). The absolute change in FVC correlated with final serum SP-D in participants receiving liraglutide (r = -0.313, P = 0.036). Stepwise multivariate regression analysis showed that final serum SP-D independently predicted changes in FVC. In conclusion, liraglutide increased FVC in patients with type 2 diabetes. This effect was associated with a significant decrease of circulating SP-D, thus pointing to a beneficial effect in the alveolar-capillary function.

Plasma profiling reveals a blood-based metabolic fingerprint of obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is a chronic, heterogeneous and multicomponent disorder with associated cardiovascular and metabolic alterations. Despite being the most common sleep-disordered breathing, it remains a significantly undiagnosed condition. OBJECTIVE: We examined the plasma metabolome and lipidome of patients with suspected OSA, aiming to identify potential diagnosis biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease. Additionally, we evaluated the impact of continuous positive airway pressure (CPAP) treatment on the circulating metabolomic and lipidomic profile. MATERIAL AND METHODS: Observational-prospective-longitudinal study including 206 consecutive subjects referred to the sleep unit. OSA was defined as an apnea-hypopnoea index ≥ 15 events/h after polysomnography (PSG). Patients treated with CPAP were followed-up for 6 months. Untargeted plasma metabolomic and lipidomic profiling was performed using liquid chromatography coulpled to massspectrometry. RESULTS: A plasma profile composed of 33 metabolites (mainly glycerophospholipids and bile acids) was identified in OSA vs. non-OSA patients. This profile correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses disclosed a 4-metabolites-signature that provided an accuracy (95% CI) of 0.98 (0.95-0.99) for OSA detection. CPAP treatment was associated with changes in 5 plasma metabolites previously altered by OSA. CONCLUSIONS: This analysis of the circulating metabolome and lipidome reveals a molecular fingerprint of OSA, which was modulated after effective CPAP treatment. Our results suggest blood-based biomarker candidates with potential application in the personalized management of OSA and suggest the activation of adaptive mechanisms in response to OSA-derived hypoxia.

Prediabetes Is Associated with Increased Prevalence of Sleep-Disordered Breathing.

Type 2 diabetes leads to severe nocturnal hypoxemia, with an increase in apnea events and daytime sleepiness. Hence, we assessed sleep breathing parameters in the prediabetes stage. A cross-sectional study conducted on 966 middle-aged subjects without known pulmonary disease (311 patients with prediabetes and 655 controls with normal glucose metabolism) was conducted. Prediabetes was defined by glycated hemoglobin (HbA1c), and a nonattended overnight home sleep study was performed. Participants with prediabetes (n = 311) displayed a higher apnea−hypopnea index (AHI: 12.7 (6.1;24.3) vs. 9.5 (4.2;19.6) events/h, p < 0.001) and hypopnea index (HI: 8.4 (4.0;14.9) vs. 6.0 (2.7;12.6) events/h, p < 0.001) than controls, without differences in the apnea index. Altogether, the prevalence of obstructive sleep apnea was higher in subjects with prediabetes than in controls (78.1 vs. 69.9%, p = 0.007). Additionally, subjects with prediabetes presented impaired measurements of the median and minimum nocturnal oxygen saturation, the percentage of time spent with oxygen saturations below 90%, and the 4% oxygen desaturation index in comparison with individuals without prediabetes (p < 0.001 for all). After adjusting for age, sex, and the presence of obesity, HbA1c correlated with the HI in the entire population (r = 0.141, p < 0.001), and the presence of prediabetes was independently associated with the AHI (B = 2.20 (0.10 to 4.31), p = 0.040) as well as the HI (B = 1.87 (0.61 to 3.14), p = 0.004) in the multiple linear regression model. We conclude that prediabetes is an independent risk factor for an increased AHI after adjusting for age, sex, and obesity. The enhanced AHI is mainly associated with increments in the hypopnea events.

Prevalence of Obstructive Sleep Apnoea and Its Association With Atherosclerotic Plaques in a Cohort of Subjects With Mild-Moderate Cardiovascular Risk.

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/m2 (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 (eß (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.

Effect of CPAP treatment on BP in resistant hypertensive patients according to the BP dipping pattern and the presence of nocturnal hypertension.

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

Long-Term Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment on Blood Pressure in Patients with Acute Coronary Syndrome: A Clinical Trial.

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/m2, 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).

Respiratory Polygraphy Patterns and Risk of Recurrent Cardiovascular Events in Patients With Acute Coronary Syndrome.

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 (SaO2), average duration of events and percentage of time with SaO2 < 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 SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 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.

The effect of chronic intermittent hypoxia in cardiovascular gene expression is modulated by age in a mice model of sleep apnea.

STUDY OBJECTIVES: Chronic intermittent hypoxia (CIH) is a major determinant in obstructive sleep apnea cardiovascular morbidity and this effect is influenced by age. The objective of the present study was to assess the differential molecular mechanisms at gene-level expression involved in the cardiovascular remodeling induced by CIH according to chronological age. METHODS: Two- and 18-month-old mice (N = 8 each) were subjected to CIH or normoxia for 8 weeks. Total messenger RNA (mRNA) was extracted from left ventricle myocardium and aortic arch, and gene expression of 46 intermediaries of aging, oxidative stress, and inflammation was measured by quantitative real-time polymerase chain reaction. RESULTS: Cardiac gene expression of Nrf2 (2.05-fold increase, p < 0.001), Sod2 (1.9-fold increase, p = 0.035), Igf1r (1.4-fold increase, p = 0.028), Mtor (1.8-fold increase, p = 0.06), Foxo3 (1.5-fold increase, p = 0.020), Sirt4, Sirt6, and Sirt7 (1.3-fold increase, p = 0.012; 1.1-fold change, p = 0.031; 1.3-fold change, p = 0.029) was increased after CIH in young mice, but not in old mice. In aortic tissue, endothelial isoform of nitric oxide synthase was reduced in young mice (p < 0.001), Nrf2 was reduced in 80% (p < 0.001) in young mice and 45% (p = 0.07) in old mice, as its downstream antioxidant target Sod2 (82% reduced, p < 0.001). IL33. CONCLUSIONS: CIH effect in gene expression is organ-dependent, and is modulated by age. CIH increased transcriptional expression of genes involved in cardioprotection and cell survival in young, but not in old mice. In aortic tissue, CIH reduced gene expression related to an antioxidant response in both young and old mice, suggesting vascular oxidative stress and a proaging process.

Sleep profile predicts the cognitive decline of mild-moderate Alzheimer's disease patients.

STUDY OBJECTIVES: To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer's disease. METHODS: Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer's disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers). RESULTS: The cohort included 125 patients with a median [IQR] of 75.0 [72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of -1.51 (95% CI: -2.43 to -0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose-response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023). CONCLUSIONS: Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer's disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline. CLINICAL TRIAL INFORMATION: Role of Hypoxia Ans Sleep Fragmentation in Alzheimer's Disease. and Sleep Fragmentation. Completed. NCT02814045.