Effect of continuous positive airway pressure on atrial remodeling and diastolic dysfunction of patients with obstructive sleep apnea and metabolic syndrome: a randomized study.

OBJECTIVE: The aim of this study was to evaluate the role of obstructive sleep apnea (OSA) treatment on heart remodeling and diastolic dysfunction in patients with metabolic syndrome (MS). METHODS: This study is a prespecified analysis of a randomized placebo-controlled trial that enrolled patients with a recent diagnosis of MS and moderate-to-severe OSA to undergo continuous positive airway pressure (CPAP) or nasal dilators (placebo) for 6 months. Patients were invited to perform a transthoracic echocardiogram by a single investigator blinded to treatment assignment. RESULTS: A total of 99 (79% men; mean [SD], age: 48 [9] years; BMI: 33 [4] kg/m2 ) completed the study. At follow-up, in the placebo group, patients had a significant increase in atrial diameter: from 39.5 (37.0-43.0) mm to 40.5 (39.0-44.8) mm (p = 0.003). CPAP prevented atrial enlargement: from 40.0 (38.0-44.0) to 40.0 (39.0-45.0) mm (p = 0.194). In patients with diastolic dysfunction at baseline, almost half had diastolic dysfunction reversibility with CPAP (in comparison with only two patients in the placebo group, p = 0.039). In the regression analysis, the chance of diastolic dysfunction reversibility by CPAP was 6.8-fold (95% CI: 1.48-50.26, p = 0.025) compared with placebo. CONCLUSIONS: In patients with MS and OSA, 6 months of CPAP therapy prevented atrial remodeling and increased the chance of diastolic dysfunction reversibility.

Effects of CPAP on Metabolic Syndrome in Patients With OSA: A Randomized Trial.

BACKGROUND: OSA is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with CPAP can revert MS. RESEARCH QUESTION: Does OSA treatment with CPAP per se have effects on the MS reversibility and the associated metabolic, adiposity and vascular parameters? STUDY DESIGN AND METHODS: The TREATOSA-MS trial is a randomized placebo-controlled trial that enrolled adult patients with a recent diagnosis of MS and moderate or severe OSA (apnea-hypopnea index [AHI], ≥ 15 events/h) to undergo therapeutic CPAP or nasal dilator strips (placebo group) for 6 months. Before and after each intervention, we measured anthropometric variables, BP, glucose, and lipid profile. To control potential-related mechanisms and consequences, we also measured adiposity biomarkers (leptin and adiponectin), body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic fat), and endothelial function. RESULTS: One hundred patients (79% men; mean age, 48 ± 9 years; BMI, 33 ± 4 kg/m2; AHI, 58 ± 29 events/h) completed the study (n = 50 per group). The mean CPAP adherence was 5.5 ± 1.5 h/night. After 6 months, most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group (18% vs 4%; OR, 5.27; 95% CI, 1.27-35.86; P = .04). In the secondary analysis, CPAP did not promote significant reductions in the individual components of MS, weight, hepatic steatosis, lipid profile, adiponectin, and leptin, but did promote a very modest reduction in visceral fat and improved endothelial function (all analyses were adjusted for baseline values). INTERPRETATION: Despite the higher rate of MS reversibility after CPAP therapy as compared with placebo, most patients retained this diagnosis. The lack of significant or relevant effects on adiposity biomarkers and depots supports the modest role of OSA in modulating MS. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02295202; URL: www. CLINICALTRIALS: gov.

Obstructive sleep apnea, sleep duration and chronic kidney disease in patients with coronary artery disease.

BACKGROUND: Limited evidence is available addressing the potential role of sleep disorders on renal function. Here, we aimed to explore the associations of obstructive sleep apnea (OSA) and sleep duration (SD) with renal function in subjects with high cardiovascular risk. METHODS: Consecutive subjects with coronary artery disease (CAD) underwent clinical evaluation, sleep study to define OSA and one-week wrist actigraphy to objectively measure SD. OSA was defined by an apnea-hypopnea index (AHI) of ≥15 events/hour. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We analyzed the associations of OSA and SD with continuous eGFR values and according to the presence of CKD (eGFR<60 mL/min/1.73 m2) after adjusting for multiple confounding factors. RESULTS: We studied 242 subjects (62.8% men). The frequency of OSA was 55.4% and the median SD was 412.8 (363.4-457.25) min. There was no difference in the eGFRs between participants with and without OSA (69.3 ± 19.1 vs. 74.6 ± 19.3 mL/min/1.73 m2, p = 0.72) and the rate of eGFR <60 mL/min/1.73 m2 (34.3% vs. 25.9%; p = 0.21). Similarly, we did not find differences in patients in eGFR for those with SD ≥ 6 h versus SD < 6 h (72.5 ± 20.3 vs. 71.4 ± 19.1 mL/min/1.73 m2, p = 0.72). In the linear regression analysis, AHI was independently associated with an eGFR<60 mL/min/1.73 m2 in the unadjusted model [-0.15 (-0.27 to -0.04)], (P = 0.01), but not in the adjusted models. Analyses of continuous SD or the stratification in SD ≥ 6 h or <6 h also revealed neutral results on eGFR. CONCLUSION: OSA severity and SD were not independently associated with CKD in subjects with CAD.

Three-year effects of bariatric surgery on obstructive sleep apnea in patients with obesity grade 1 and 2: a sub-analysis of the GATEWAY trial.

BACKGROUND: Most of the evidence on bariatric surgery on obstructive sleep apnea (OSA) is based on observational studies and/or short-term follow-up in patients with obesity grade 3. SUBJECTS/METHODS: This randomized study compared the effects of roux-en-Y gastric bypass (RYGB) or usual care (UC) on OSA severity in patients with obesity grade 1-2. Mild, moderate, and severe OSA was defined by the apnea-hypopnoea index (AHI): 5-14.9; 15-29.9, and ≥30 events/h, respectively. OSA remission was defined by converting any form of OSA into normal AHI (<5 events/h). RESULTS: After 3-year of follow-up, the body-mass index increased in the UC while decreased in the RYGB group: +1.7 (-1.9; 2.7) versus -10.6 (-12.7; -9.2) kg/m2, respectively. The AHI increased by 5 (-4.2; 12.7) in the UC group while reduced in the RYGB group to -13.2 (-22.7; -7) events/h. UC significantly increase the frequency of moderate OSA (from 15.4 to 46.2%). In contrast, RYGB had a huge impact on reaching no OSA status (from 4.2 to 70.8%) in parallel to a decrease of moderate (from 41.7 to 8.3%) and severe OSA (from 20.8 to 0%). CONCLUSIONS: RYGB is an attractive strategy for mid-term OSA remission or decrease moderate-to-severe forms of OSA in patients with obesity grade 1-2.

OSA, Short Sleep Duration, and Their Interactions With Sleepiness and Cardiometabolic Risk Factors in Adults: The ELSA-Brasil Study.

BACKGROUND: OSA and short sleep duration (SSD) are frequently associated with daytime symptoms and cardiometabolic deregulation. However, the vast majority of studies addressing OSA have not evaluated SSD, and vice versa. Our aim was to evaluate the association of OSA, SSD, and their interactions with sleepiness and cardiometabolic risk factors in a large cohort of adults. METHODS: Consecutive subjects from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) participated in clinical evaluations, sleep questionnaires, home sleep monitoring, and actigraphy. OSA was defined as an apnea-hypopnea index ≥ 15 events/hour. SSD was defined by a mean sleep duration < 6 h. RESULTS: Data from 2,064 participants were used in the final analysis (42.8% male; mean age, 49 ± 8 years). The overall frequency of OSA and SSD were 32.9% and 27.2%, respectively. Following an adjustment for multiple confounding factors, excessive daytime sleepiness was independently associated with SSD (OR, 1.448; 95% CI, 1.172-1.790) but not with OSA (OR, 1.107; 95% CI, 0.888-1.380). The SSD interaction with OSA was not significant. Prevalent obesity (OR, 3.894; 95% CI, 3.077-4.928), hypertension (OR, 1.314; 95% CI, 1.035-1.667), and dyslipidemia (OR, 1.251; 95% CI, 1.006-1.555) were independently associated with OSA but not with SSD. Similarly, the interactions of OSA with SSD were not significant. An additional analysis using < 5 h for SSD or continuous sleep duration did not change the lack of association with the cardiometabolic risk factors. CONCLUSIONS: Objective SSD but not OSA was independently associated with daytime sleepiness. By contrast, OSA, but not SSD, was independently associated with obesity, hypertension, and dyslipidemia.

Nondipping Blood Pressure Patterns Predict Obstructive Sleep Apnea in Patients Undergoing Ambulatory Blood Pressure Monitoring.

A nondipping blood pressure (BP) pattern is common in patients with obstructive sleep apnea (OSA). However, it is unclear how useful a nondipping BP pattern is in screening for OSA. In this cross-sectional study, we recruited consecutive patients with clinical indications for performing ambulatory BP monitoring evaluating the following dipping patterns: (1) normal: ≥10% but <20%; (2) extreme: ≥20%; (3) reduced: ≥0% but <10%; and (4) reverse (riser): <0%. Sleep questionnaires and sleep studies were performed within 7 days after ambulatory BP monitoring. OSA was defined as an apnea-hypopnea index ≥15 events/h. We evaluated 153 patients (OSA frequency, 50.3%). Patients with OSA had higher BPs during sleep, were taking more antihypertensive drugs, and more frequently used hypertensive drugs during the night than patients without OSA. Considering systolic BP, the frequency of OSA in patients with reverse dippers (73.5%) was higher than normal (37.3%), extreme (46.2%), and reduced dippers (49.1%; P=0.012). For diastolic BP, OSA was more common in reduced (66.7%) and reverse dippers (69.6%) as compared to normal (41.4%) or extreme dippers (33.3%; P=0.007). In the regression analysis, reverse systolic dipper was independently associated with OSA (odds ratio, 3.92; 95% CI, 1.31-11.78). Both reduced and reverse diastolic dippers increased the likelihood of OSA for 2.7-fold and 3.5-fold, respectively. Snoring and positive sleep questionnaire findings were associated with a modest increase in the accuracy of reverse dipping pattern for predicting OSA. In conclusion, reverse systolic, as well as reduced and reverse diastolic dippers are independently associated with OSA.

Performance of NoSAS score versus Berlin questionnaire for screening obstructive sleep apnoea in patients with resistant hypertension

ABSTRACT: Obstructive sleep apnoea (OSA) is the main secondary form associated with resistant hypertension (RH), but it is largely underdiagnosed and consequently undertreated in clinical practice. The Berlin questionnaire (BQ) is a useful tool among general population, but seems to not perform well among patients with RH. Recently, NoSAS score was validated in a large population, however, has not been tested in the cardiovascular scenario. Thus, we aimed to compare BQ versus the NoSAS score as screening tools for OSA in RH. In the present study, patients with confirmed diagnosis of RH were invited to perform polysomnography. OSA was diagnosed by an apnoea-hypopnoea index (AHI) ≥15 events/h. BQ and NoSAS were applied in a blinded way. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of the two sleep questionnaires to detect OSA in RH. The frequency of OSA was 64%. The BQ presented a better sensitivity (91 vs. 72%) and higher values of NPV (67 vs. 54%) than NoSAS score. In contrast, the NoSAS score had higher specificity for excluding OSA (58 vs. 33%) and higher PPV (75 vs. 70%). Compared to the BQ, NoSAS score had a better AUC (0.55 vs. 0.64) but these values are in the fail to poor accuracy range. In conclusion, both BQ and NoSAS score had low accuracy for detecting OSA in RH. Considering the high frequency of OSA, objective sleep study may be considered in these patients.

Performance of NoSAS score versus Berlin questionnaire for screening obstructive sleep apnoea in patients with resistant hypertension.

Obstructive sleep apnoea (OSA) is the main secondary form associated with resistant hypertension (RH), but it is largely underdiagnosed and consequently undertreated in clinical practice. The Berlin questionnaire (BQ) is a useful tool among general population, but seems to not perform well among patients with RH. Recently, NoSAS score was validated in a large population, however, has not been tested in the cardiovascular scenario. Thus, we aimed to compare BQ versus the NoSAS score as screening tools for OSA in RH. In the present study, patients with confirmed diagnosis of RH were invited to perform polysomnography. OSA was diagnosed by an apnoea-hypopnoea index (AHI) ≥15 events/h. BQ and NoSAS were applied in a blinded way. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of the two sleep questionnaires to detect OSA in RH. The frequency of OSA was 64%. The BQ presented a better sensitivity (91 vs. 72%) and higher values of NPV (67 vs. 54%) than NoSAS score. In contrast, the NoSAS score had higher specificity for excluding OSA (58 vs. 33%) and higher PPV (75 vs. 70%). Compared to the BQ, NoSAS score had a better AUC (0.55 vs. 0.64) but these values are in the fail to poor accuracy range. In conclusion, both BQ and NoSAS score had low accuracy for detecting OSA in RH. Considering the high frequency of OSA, objective sleep study may be considered in these patients.

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study.

BACKGROUND: Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS: A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION: There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention.

BACKGROUND: There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. METHODS AND RESULTS: The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10-2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. CONCLUSIONS: OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.

Management of Hypertension in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is considered to be a secondary form of hypertension and in clinical practice OSA is frequently associated with hypertension, even if proof of causality cannot be established. Growing evidence suggests that OSA is associated with worse blood pressure control, alterations in night-time blood pressure dipping, increased target organ damage, and arterial stiffness in patients with hypertension. This review summarizes the current evidence for managing hypertension in patients with OSA. Particular focus will be devoted to discuss the impact of lifestyle changes, preferences for anti-hypertensive treatment in patients with OSA, and the effects of OSA treatment with continuous positive airway pressure on blood pressure.