Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea–hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370.)

Poor adherence to continuous positive airway pressure (CPAP) commonly affects therapeutic response in obstructive sleep apnea (OSA). We aimed to determine predictors of adherence to CPAP among participants of the Sleep Apnea and cardioVascular Endpoints (SAVE) trial. SAVE was an international, randomized, open trial of CPAP plus usual care versus usual care (UC) alone in participants (45–75 years) with co-occurring moderate-to-severe OSA (≥12 episodes/h of ≥4% oxygen desaturation) and established cardiovascular (CV) disease. Baseline sociodemographic, health and lifestyle factors, OSA symptoms, and 1-month change in daytime sleepiness, as well as CPAP side effects and adherence (during sham screening, titration week, and in the first month), were entered in univariate linear regression analyses to identify predictors of CPAP adherence at 24 months. Variables with p <0.2 were assessed for inclusion in a multivariate linear mixed model with country, age, and sex included a priori and site as a random effect. Significant univariate predictors of adherence at 24 months in 1,121 participants included: early adherence measures, improvement in daytime sleepiness at 1 month, fixed CPAP pressure, some measures of OSA severity, cardiovascular disease history, breathing pauses, and very loud snoring. While observed adherence varied between countries, adherence during sham screening, initial titration, and the first month of treatment retained independent predictive value in the multivariate model along with fixed CPAP pressure and very loud snoring. Early CPAP adherence had the greatest predictive value for identifying those at highest risk of non-adherence to long-term CPAP therapy. SAVE is registered with clinicaltrials.gov (NCT00738179).

Obstructive sleep apnea (OSA) can result in hypertension and significantly increase cardiovascular morbidity and mortality. There are few reports on the long-term effects of continuous positive airway pressure (CPAP) on blood pressure in patients with uncontrolled hypertension with coronary heart disease (CHD) and OSA. We conducted a prospective, long-term follow-up study in 83 patients with uncontrolled hypertension, CHD, and OSA randomized to control or CPAP groups. Daytime systolic blood pressure (SBP), diastolic blood pressure (DBP), and severe cardiovascular and cerebrovascular events (SCCEs) were recorded at baseline and follow-up. Seventy-three patients completed the study with a median follow-up of 36 (interquartile range = 24–54) months. The 2 groups had similar characteristics at baseline. CPAP was used for 4.5±1.1 hour/night. SBP in the CPAP group was significantly reduced at follow-up (143±7mm Hg vs. 139±7mm Hg, P = 0.04), and SBP decreased by 8mm Hg (95% confidence interval = 1.4–9.9; P = 0.01). Hypertension control was improved (CPAP, 69.4% for CPAP users vs. 43.2% for control subjects; P = 0.02); however, DBP did not reach statistical difference between the groups (81±10mm Hg vs. 79±8mm Hg; P = 0.49). In the CPAP group, the Epworth Sleepiness Scale was markedly reduced (7.0±3.4 vs. 3.7±2.3; P < 0.001). There was 1 SCCE in the CPAP group (heart failure), and 5 SCCEs in the control group (acute myocardial infarction: 2 (with 1 death); stroke: 3), but there was no significant difference identified. Long-term CPAP application in uncontrolled hypertension with CHD and OSA significantly reduced daytime SBP, improved hypertension control and daytime sleepiness, and decreased the trend in SCCEs compared with control subjects. ClinicalTrials.gov NCT02059993.

Obstructive sleep apnoea (OSA) is a common comorbidity in patients with cardiovascular (CV) disease. We aimed to identify specific OSA clinical phenotypes relating to risks of serious CV events and response to continuous positive airway pressure (CPAP) treatment. Post-hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) study in participants with moderate-to-severe OSA and coronary artery disease (CAD) and/or cerebrovascular disease (CeVD) randomised to CPAP plus usual care or usual care alone. Latent class analysis (LCA) was used to identify OSA clinical phenotypes among 2649 (out of 2687 total) patients with complete data on 19 patient-centered variables, supported by Bayesian information criteria and clinical interpretability. Cox regression models were used to evaluate risks of composite cardiac and stroke outcome events in phenotype groups. Preferential response to CPAP treatment was evaluated using interaction terms as well as the Chi-square test. LCA identified four OSA clinical phenotypes: CAD alone and with diabetes mellitus (CAD + DM), and CeVD alone and with DM (CeVD + DM), in 39%, 15%, 37% and 9% of participants, respectively. The rates of composite CV events were the highest in CAD + DM phenotype (HR 2.08, 95% CI 1.57-2.76) and for stroke were highest in CeVD + DM phenotype (HR 6.84, 95% CI 3.77-12.42). Adherence to CPAP treatment (nil or < 4 h vs ≥ 4 h in the first two years of the study) was shown to influence the risk of composite CV outcome in the phenotypes (P-interaction = 0.04); CPAP adherent patients of the CeVD + DM phenotype had the lowest risk of CV outcome (P = 0.02). High risk clinical phenotypes were identified in relation to CV events and response to CPAP treatment, which may allow improved targeting of therapies in OSA patients. The National Health and Medical Research Council (NHMRC) of Australia, Fisher & Paykel Healthcare, and ResMed.

Whether continuous positive airway pressure (CPAP) treatment can improve depression or anxiety symptoms in obstructive sleep apnoea (OSA) patients remains uncertain. Secondary analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, combined with a systematic review of randomised evidence. The SAVE secondary analyses involved 2410 patients with co-existing moderate-severe OSA and established cardiovascular disease randomly allocated to CPAP treatment plus usual care or usual care alone and followed up for 3·7 (SD 1·6) years. We evaluated the effect of CPAP treatment on depression and anxiety caseness (scores ≥ 8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A]) for OSA patients. CPAP treatment was associated with reduced odds of depression caseness (adjusted odds ratio [OR] 0·80, 95% confidence interval [CI] 0·65-0·98, P = 0·031) compared to usual care in the SAVE trial and the treatment effect was greater in those with pre-existing depression symptoms. A systematic review of 20 randomised trials including 4255 participants confirmed a benefit of CPAP in reducing depression symptoms in OSA patients: the overall effect (standardised mean difference) was - 0·18 (95% CI - 0·24 to - 0·12). No effect of CPAP treatment on anxiety caseness was found both in patients of the SAVE study (adjusted OR 0·98, 95% CI 0·78-1·24, P = 0·89) and the systematic review. CPAP reduces depression symptoms in patients with co-existing OSA and CVD independently of improvements in sleepiness.

Background: Balloon pulmonary angioplasty (BPA) has been demonstrated to improve cardiac function and exercise capacity in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its instant impact on cardiopulmonary function has seldom been evaluated. This study aims to determine the safety and efficacy of BPA and its immediate and lasting effects on cardiopulmonary function among CTEPH patients.Methods: From May 2018 to January 2019, patients with inoperable CTEPH who underwent BPA sessions were consecutively enrolled. Hemodynamics were measured by right heart catheterization, selective pulmonary angiography and BPA were successively conducted. Hemodynamic variables, WHO functional class (WHO-FC), 6-min walk distance (6MWD) and serum NT-proBNP were evaluated before and after BPA sessions during hospitalization. Pulmonary function testing (PFT) and cardiopulmonary exercise testing (CPET) were performed within 1–3 days pre and post BPA to evaluate the effect of BPA on cardiopulmonary function.Results: Twenty-five patients with inoperable CTEPH who underwent a total of forty BPA sessions were consecutively enrolled. A total of 183 segmental or subsegmental vessels (4.6 ± 1.9 vessels per session) in 137 segments (3.4 ± 1.6 segments per session) were dilated. No procedure-related complications occurred. Instant hemodynamics, WHO-FC, 6MWD and NT-proBNP were all significantly improved after a single BPA session. Significant improvement in cardiopulmonary function was also evident as assessed by PFT indexes (forced vital capacity, forced expiratory volume in the first second, maximal voluntary ventilation) and CPET parameters (peak work rate, peak VO₂, oxygen uptake efficiency slope). Further analysis among ten CTEPH patients receiving multiple BPA sessions (2–4 sessions) indicated BPA resulted in lasting improvements in hemodynamics and cardiopulmonary function.Conclusions: BPA, a safe and effective approach, can bring instant improvements after a single session and lasting benefits after multiple sessions to hemodynamics and cardiopulmonary function for patients with inoperable CTEPH.