Mechanisms of heart failure and chronic kidney disease protection by SGLT2 inhibitors in nondiabetic conditions.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for type 2 diabetes (T2D) treatment, have demonstrated significant cardiovascular and renal benefits in heart failure (HF) and chronic kidney disease (CKD), irrespective of T2D. This review provides an analysis of the multifaceted mechanisms underlying the cardiorenal benefits of SGLT2i in HF and CKD outside of the T2D context. Eight major aspects of the protective effects of SGLT2i beyond glycemic control are explored: (i) the impact on renal hemodynamics and tubuloglomerular feedback; (ii) the natriuretic effects via proximal tubule Na+/H+ exchanger NHE3 inhibition; (iii) the modulation of neurohumoral pathways with evidence of attenuated sympathetic activity; (iv) the impact on erythropoiesis, not only in the context of local hypoxia, but also systemic inflammation and iron regulation; (v) the uricosuria and mitigation of the hyperuricemic environment in cardiorenal syndromes; (vi) the multiorgan metabolic reprogramming including the potential induction of a fasting-like state, improvement in glucose and insulin tolerance and stimulation of lipolysis and ketogenesis; (vii) the vascular endothelial growth factor A (VEGF-A) upregulation and angiogenesis, and (viii) the direct cardiac effects. The intricate interplay between renal, neurohumoral, metabolic, and cardiac effects underscore the complexity of SGLT2i actions and provides valuable insights into their therapeutic implications for HF and CKD. Furthermore, this review sets the stage for future research to evaluate the individual contributions of these mechanisms in diverse clinical settings.

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

Optimal cardiovascular health is associated with slower cognitive decline.

BACKGROUND: Life's Simple 7, a lifestyle and cardiovascular index associated with cognition, has been updated to Life's Essential 8 (LE8) to include sleep. LE8 has been related to cardiovascular outcomes but its association with cognition is unclear. METHODS: In this longitudinal analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), LE8 score was based on health behaviors (diet, physical activity, nicotine exposure, and sleep health) as well as health-related factors (body mass index, blood lipids, blood glucose, and blood pressure). Cognition was assessed in three waves, 4 years apart, using the Consortium to Establish a Registry for Alzheimer's Disease - Word List, semantic and phonemic verbal fluency, the Trail-Making Test B (TMT-B), and a global composite score. We used linear mixed-model analysis, inverse probability weighting, and interaction analysis. RESULTS: At baseline, the mean age of the study cohort was 51.4 ± 8.9 years, 56% were women, and 53% were White. Higher baseline LE8 scores were associated with slower decline in global cognition (ß = 0.001, 95% confidence interval [CI] 0.001, 0.002; p < 0.001), memory (ß = 0.001, 95% CI 0.000, 0.002; p = 0.013), verbal fluency (ß = 0.001, 95% CI 0.000, 0.002; p = 0.003), and TMT-B (ß = 0.004, 95% CI 0.003, 0.005; p < 0.001). This association was mainly driven by LE8 health factors, particularly blood glucose and blood pressure. Age, sex, and race were modifiers of the association between LE8 and global cognitive decline (p < 0.001), suggesting it was more pronounced in older, male, and Black participants. CONCLUSIONS: Higher baseline LE8 scores were associated with slower global and domain-specific cognitive decline during 8 years of follow-up, mainly due to health factors such as blood glucose and blood pressure. Sociodemographic factors were modifiers of this association.

Situational analysis of hypertension management at primary health care level in São Paulo, Brazil: population, healthcare professional and health system perspectives.

BACKGROUND: Government-led, population-wide initiatives are crucial for advancing the management of hypertension - a leading cause of cardiovascular disease (CVD) morbidity and mortality. An urban population health initiative was conducted against this backdrop, focussing on hypertension in the primary health system in São Paulo, Brazil. Within the frame of the initiative and under the supervision and leadership of the municipal health authorities, a situational analysis was conducted on the needs in hypertension management, marking the first phase of a Design Thinking process. This article describes the situational analysis process and presents the identified elements to be strengthened considering hypertension diagnosis, treatment and control. METHODS: First, a mixed-methods approach was used, starting with a literature review of municipal hypertension data followed by meetings (N = 20) with the local public health administration to assess health system level components. To investigate activities on hypertension diagnosis, treatment and control, nine primary healthcare units were selected from two districts of São Paulo city- Itaquera and Penha- which received an online form addressed to managers, participated in conversation circles of staff and patients, and underwent shadowing of community health agents. RESULTS: Data gave rise to two main outputs: (i) a patient care journey map; and (ii) a matrix summarizing the identified needs at patient, healthcare professional and health system level for diagnosis, treatment and control of hypertension. Patient awareness and knowledge of hypertension was found to be insufficient and its management needs to be improved. For health professionals, disease awareness, technical training, more time dedicated to patients, and simplified guidelines and clinical decision-making tools for hypertension management were identified as principal needs. The situational analysis found that the healthcare systems efficiency might be improved by establishing defined treatment and care delivery goals with a focus on outcomes and implemented through action plans. CONCLUSIONS: This situational analysis identified several needs related to hypertension control in São Paulo that are in line with global challenges to improve the control of CVD risk factors. Findings were also confirmed locally in an expansion phase of this situational analysis to additional primary care facilities. As a consequence, solutions were designed, promptly taken up and implemented by the municipal health secretariat.

Comorbid association of obstructive sleep apnea (OSA) and thrombotic primary antiphospholipid syndrome (tPAPS): A more severe phenotype?

OBJECTIVE: We aimed to evaluate the frequency of obstructive sleep apnea (OSA) in patients with thrombotic primary antiphospholipid syndrome (tPAPS), to investigate the performance of screening tools for OSA in this scenario and to compare clinical/laboratorial differences in tPAPS patients with and without OSA. METHODS: We consecutively enrolled patients with tPAPS to undergo sleep studies using a portable monitor. OSA was defined as apnea-hypopnea index ≥15 events/h. Frequency of OSA in tPAPS was evaluated and compared with age-, gender-, and BMI-matched controls (1:3 ratio) from the Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Next, we tested the performance of three different screening tools for assessing OSA in patients with tPAPS. Finally, patients with tPAPS were stratified according to OSA status comparing their clinical and laboratory characteristics (including damage burden measured by Damage Index for Antiphospholipid Syndrome [DIAPS] and biomarkers associated with thrombosis) using standard statistical procedures. RESULTS: Fifty-two patients were included for analysis (females: 82.7%; mean age: 48 ± 14 years; body-mass index: 31.1 ± 6.5 Kg/m2; 25% with moderate-severe OSA). When compared to matched controls from ELSA-Brasil (n = 115), there was no significant differences in the frequencies of OSA (tPAPS: 12/42 [28.6%] vs. controls: 35/115 [30.4%], p = 0.821). Among screening tools, NoSAS had the highest area under ROC curve (AUC 0.806, CI 95% 0.672-0.939, p = 0.001), followed by STOP-Bang (AUC 0.772, CI 95% 0.607-0.938, p = 0.004). Patients with comorbid tPAPS and OSA presented higher levels of von Willebrand factor (vWF) (median 38.9 vs. 32.6, p = 0.038) and DIAPS (median 5 vs. 2, p = 0.020), when compared to those without OSA. OSA remained statistically associated with higher DIAPS, even after controlling for age, disease duration and BMI. CONCLUSION: OSA is common in patients with tPAPS, with rates comparable to a non-referred population. Both NoSAS and STOP-Bang scores seems to be useful for screening OSA in these patients. Patients with tPAPS+OSA had higher damage burden and higher levels of vWF, which might suggest a more severe phenotype of tPAPS in this scenario.

Association between objective sleep measures and cognitive performance: a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study.

Sleep disturbances often co-exist, which challenges our understanding of their potential impact on cognition. We explored the cross-sectional associations of insomnia and objective measures of sleep with cognitive performance in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study stratified by middle-aged and older adults. Participants aged ≥55 years underwent cognitive evaluations, polygraphy for 1 night, and actigraphy for 7 days. Insomnia was evaluated using the Clinical Interview Scheduled Revised. Obstructive sleep apnea (OSA) and short sleep duration (SSD) were defined by an apnea-hypopnea index (AHI) of ≥15 events/h and <6 h/ night, respectively. In 703 participants (mean [SD] age 62 [6] years, 44% men), cognition was evaluated using a 10-word list, verbal fluency, and trail-making tests. The frequencies of insomnia, SSD, and OSA were 11%, 24%, and 33%, respectively. In all, 4% had comorbid OSA and insomnia, and 11% had both OSA and SSD. Higher wake after sleep onset (ß = -0.004, 95% confidence interval [CI] -0.008, -0.001) and the number of awakenings (ß = -0.006, 95% CI -0.012, -0.001) were associated with worse verbal fluency performance. Compared to those without insomnia, older participants with insomnia had worse global performance (ß = -0.354, 95% CI -0.671, -0.038). Insomnia was an effect modifier in the associations between AHI and executive function performance (p for the interaction between insomnia and AHI = 0.004) and between oxygen saturation <90% and memory performance (p for the interaction between insomnia and oxygen saturation = 0.02). Although some associations between sleep measures and cognition were significant, they should be considered with caution due to the large sample size and multiple testing performed in this study.

Pharmacological treatment for central sleep apnoea in adults.

BACKGROUND: The term central sleep apnoea (CSA) encompasses diverse clinical situations where a dysfunctional drive to breathe leads to recurrent respiratory events, namely apnoea (complete absence of ventilation) and hypopnoea sleep (insufficient ventilation) during sleep. Studies have demonstrated that CSA responds to some extent to pharmacological agents with distinct mechanisms, such as sleep stabilisation and respiratory stimulation. Some therapies for CSA are associated with improved quality of life, although the evidence on this association is uncertain. Moreover, treatment of CSA with non-invasive positive pressure ventilation is not always effective or safe and may result in a residual apnoea-hypopnoea index. OBJECTIVES: To evaluate the benefits and harms of pharmacological treatment compared with active or inactive controls for central sleep apnoea in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 August 2022. SELECTION CRITERIA: We included parallel and cross-over randomised controlled trials (RCTs) that evaluated any type of pharmacological agent compared with active controls (e.g. other medications) or passive controls (e.g. placebo, no treatment or usual care) in adults with CSA as defined by the International Classification of Sleep Disorders 3rd Edition. We did not exclude studies based on the duration of intervention or follow-up. We excluded studies focusing on CSA due to periodic breathing at high altitudes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were central apnoea-hypopnoea index (cAHI), cardiovascular mortality and serious adverse events. Our secondary outcomes were quality of sleep, quality of life, daytime sleepiness, AHI, all-cause mortality, time to life-saving cardiovascular intervention, and non-serious adverse events. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included four cross-over RCTs and one parallel RCT, involving a total of 68 participants. Mean age ranged from 66 to 71.3 years and most participants were men. Four trials recruited people with CSA associated with heart failure, and one study included people with primary CSA. Types of pharmacological agents were acetazolamide (carbonic anhydrase inhibitor), buspirone (anxiolytic), theophylline (methylxanthine derivative) and triazolam (hypnotic), which were given for between three days and one week. Only the study on buspirone reported a formal evaluation of adverse events. These events were rare and mild. No studies reported serious adverse events, quality of sleep, quality of life, all-cause mortality, or time to life-saving cardiovascular intervention. Carbonic anhydrase inhibitors versus inactive control Results were from two studies of acetazolamide versus placebo (n = 12) and acetazolamide versus no acetazolamide (n = 18) for CSA associated with heart failure. One study reported short-term outcomes and the other reported intermediate-term outcomes. We are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce cAHI in the short term (mean difference (MD) -26.00 events per hour, 95% CI -43.84 to -8.16; 1 study, 12 participants; very low certainty). Similarly, we are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce AHI in the short term (MD -23.00 events per hour, 95% CI -37.70 to 8.30; 1 study, 12 participants; very low certainty) or in the intermediate term (MD -6.98 events per hour, 95% CI -10.66 to -3.30; 1 study, 18 participants; very low certainty). The effect of carbonic anhydrase inhibitors on cardiovascular mortality in the intermediate term was also uncertain (odds ratio (OR) 0.21, 95% CI 0.02 to 2.48; 1 study, 18 participants; very low certainty). Anxiolytics versus inactive control Results were based on one study of buspirone versus placebo for CSA associated with heart failure (n = 16). The median difference between groups for cAHI was -5.00 events per hour (IQR -8.00 to -0.50), the median difference for AHI was -6.00 events per hour (IQR -8.80 to -1.80), and the median difference on the Epworth Sleepiness Scale for daytime sleepiness was 0 points (IQR -1.0 to 0.00). Methylxanthine derivatives versus inactive control Results were based on one study of theophylline versus placebo for CSA associated with heart failure (n = 15). We are uncertain whether methylxanthine derivatives compared to inactive control reduce cAHI (MD -20.00 events per hour, 95% CI -32.15 to -7.85; 15 participants; very low certainty) or AHI (MD -19.00 events per hour, 95% CI -30.27 to -7.73; 15 participants; very low certainty). Hypnotics versus inactive control Results were based on one trial of triazolam versus placebo for primary CSA (n = 5). Due to very serious methodological limitations and insufficient reporting of outcome measures, we were unable to draw any conclusions regarding the effects of this intervention. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of pharmacological therapy in the treatment of CSA. Although small studies have reported positive effects of certain agents for CSA associated with heart failure in reducing the number of respiratory events during sleep, we were unable to assess whether this reduction may impact the quality of life of people with CSA, owing to scarce reporting of important clinical outcomes such as sleep quality or subjective impression of daytime sleepiness. Furthermore, the trials mostly had short-term follow-up. There is a need for high-quality trials that evaluate longer-term effects of pharmacological interventions.

Influence of the device used for obstructive sleep apnea diagnosis on body position: a comparison between polysomnography and portable monitor.

PURPOSE: Different devices have been used for the diagnosis of obstructive sleep apnea (OSA), which differ in the number of sensors used. The numerous sensors used in more complex sleep studies such as in-lab polysomnography may influence body position during sleep. We hypothesized that patients submitted to in-lab polysomnography (PSG) would spend more time in the supine position than patients submitted to an ambulatory Portable Monitor (PM) sleep study. METHODS: Body position during PSG and PM studies was compared among two distinct groups of patients matched for age, body-mass index (BMI), apnea-hypopnea index (AHI), and gender. Predictors of time spent in the supine position were determined using a multiple linear regression model. RESULTS: Of 478 participants who underwent either PSG or PM studies, mean age: 61[43-66] years; males: 43.9%; BMI: 28.4[26.1-31.1]kg/m2; AHI 14[7-27] events/hour). Participants who underwent PSG studies spent more time in the supine position (41[16-68]% than participants who underwent PM studies (34[16-51]%), P = 0.014. Participants with OSA spent more time in the supine position than participants without OSA, both among the PSG and PM groups P < 0.05). Gender, BMI, OSA severity, and sleep study type were independent predictors of time spent in the supine position. CONCLUSION: In-lab PSG may increase time spent in the supine position and overestimate OSA severity compared to a PM sleep study. OSA diagnosis is also associated with increased time spent in the supine position. The potential influence on the sleeping position should be taken into account when choosing among the different sleep study types for OSA diagnosis.

What is the effect of catecholamines on diastolic function in patients with pheochromocytoma and paraganglioma?

Pheochromocytoma is a rare form of secondary hypertension characterized by excessive production of catecholamines typically due to a benign tumor in the adrenal medulla. Among the potential cardiac repercussions of pheochromocytoma and paraganglioma, previous studies described echocardiographic abnormalities such as dynamic left ventricular outflow tract obstruction (i), cardiomyopathy (ii, iii, iv), reversible dilatation of the left ventricle (v) and left ventricular functional changes (vi) in patients with pheochromocytoma.

Carotid intima-media thickness and flow-mediated dilation do not predict acute in-hospital outcomes in patients hospitalized with COVID-19.

Studies have suggested a potential role of endothelial dysfunction and atherosclerosis in the pathophysiology of COVID-19. Herein, we tested whether brachial flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT) measured upon hospital admission are associated with acute in-hospital outcomes in patients hospitalized with COVID-19. A total of 211 patients hospitalized with COVID-19 were submitted to assessments of FMD and mean and maximum cIMT (cIMTmean and cIMTmax) within the first 72 h of hospital admission. Study primary outcome was a composite of intensive care unit admission, mechanical ventilation, or death during the hospitalization. These outcomes were also considered independently. Thrombotic events were included as a secondary outcome. Odds ratios (ORs) and confidence intervals (CIs) were calculated using unadjusted and adjusted multivariable logistic regression models. Eighty-eight (42%) participants demonstrated at least one of the composite outcomes. cIMTmean and cIMTmax were predictors of mortality and thrombotic events in the univariate analysis (cIMTmean and mortality: unadjusted OR 12.71 [95% CI 1.71-94.48]; P = 0.014; cIMTmean and thrombotic events: unadjusted OR 11.94 [95% CI 1.64-86.79]; P = 0.015; cIMTmax and mortality: unadjusted OR 8.47 [95% CI 1.41-51.05]; P = 0.021; cIMTmax and thrombotic events: unadjusted OR 12.19 [95% CI 2.03-73.09]; P = 0.007). However, these associations were no longer present after adjustment for potential confounders (P > 0.05). In addition, FMD% was not associated with any outcome. In conclusion, cIMT and FMD are not independent predictors of clinical outcomes in patients hospitalized with COVID-19. These results suggest that subclinical atherosclerosis and endothelial dysfunction may not be the main drivers of COVID-19 complications in patients hospitalized with COVID-19.NEW & NOTEWORTHY Studies have suggested a role of endothelial dysfunction and atherosclerosis in COVID-19 pathophysiology. In this prospective cohort study, we assessed the prognostic value of carotid intima-media thickness (IMT) and flow-mediated dilation (FMD) in patients with COVID-19. Carotid IMT and FMD were not independent predictors of major outcomes. These results suggest that other risk factors may be the main drivers of clinical outcomes in patients with COVID-19.

Obstructive Sleep Apnea, Sleep Duration, and Associated Mediators With Carotid Intima-Media Thickness: The ELSA-Brasil Study.

[Figure: see text].

Non-invasive positive pressure ventilation for central sleep apnoea in adults.

BACKGROUND: Central sleep apnoea (CSA) is characterised by abnormal patterns of ventilation during sleep due to a dysfunctional drive to breathe. Consequently, people with CSA may present poor sleep quality, sleep fragmentation, inattention, fatigue, daytime sleepiness, and reduced quality of life. OBJECTIVES: To assess the effectiveness and safety of non-invasive positive pressure ventilation (NIPV) for the treatment of adults with CSA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Scopus on 6 September 2021. We applied no restrictions on language of publication. We also searched clinical trials registries for ongoing and unpublished studies, and scanned the reference lists of included studies to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) reported in full text, those published as abstract only, and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias of the included studies using the Cochrane risk of bias tool version 1.0, and the certainty of the evidence using the GRADE approach. In the case of disagreement, a third review author was consulted. MAIN RESULTS: We included 15 RCTs with a total of 1936 participants, ranging from 10 to 1325 participants. All studies had important methodological limitations. We assessed most studies (11 studies) as at high risk of bias for at least one domain, and all studies as at unclear risk of bias for at least two domains. The trials included participants aged > 18 years old, of which 70% to 100% were men, who were followed from one week to 60 months. The included studies assessed the effects of different modes of NIPV and CSA. Most participants had CSA associated with chronic heart failure. Because CSA encompasses a variety of causes and underlying clinical conditions, data were carefully analysed, and different conditions and populations were not pooled. The findings for the primary outcomes for the seven evaluated comparisons are presented below.  Continuous positive airway pressure (CPAP) plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the short term, CPAP plus best supportive care may reduce central apnoea hypopnoea index (AHI) (mean difference (MD) -14.60, 95% confidence interval (CI) -20.11 to -9.09; 1 study; 205 participants). However, CPAP plus best supportive care may result in little to no difference in cardiovascular mortality compared to best supportive care alone. The evidence for the effect of CPAP plus best supportive care on all-cause mortality is very uncertain. No adverse effects were observed with CPAP, and the results for adverse events in the best supportive care group were not reported. Adaptive servo ventilation (ASV) versus CPAP in CSA associated with chronic heart failure The evidence is very uncertain about the effect of ASV versus CPAP on quality of life evaluated in both the short and medium term. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CSA associated with chronic heart failure In the short term, ASV may result in little to no difference in central AHI. No adverse events were detected with ASV, and the results for adverse events in the bilevel ventilation group were not reported. ASV plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the medium term, ASV plus best supportive care may reduce AHI compared to best supportive care alone (MD -20.30, 95% CI -28.75 to -11.85; 1 study; 30 participants). In the long term, ASV plus best supportive care likely increases cardiovascular mortality compared to best supportive care (risk ratio (RR) 1.25, 95% CI 1.04, 1.49; 1 study; 1325 participants). The evidence suggests that ASV plus best supportive care may result in little to no difference in quality of life in the short, medium, and long term, and in all-cause mortality in the medium and long term. Data on adverse events were evaluated but not reported. ASV plus best supportive care versus best supportive care in CSA with acute heart failure with preserved ejection fraction Only adverse events were reported for this comparison, and no adverse events were recorded in either group. ASV versus CPAP maintenance in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -4.10, 95% CI -6.67 to -1.53; 1 study; 60 participants), but may result in little to no difference in quality of life. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -8.70, 95% CI -11.42 to -5.98; 1 study; 30 participants) compared to bilevel ventilation. Data on adverse events were not reported, and it is not clear whether data were sought but not found. AUTHORS' CONCLUSIONS: CPAP plus best supportive care may reduce central AHI in people with CSA associated with chronic heart failure compared to best supportive care alone. Although ASV plus best supportive care may reduce AHI in people with CSA associated with chronic heart failure, it likely increases cardiovascular mortality in these individuals. In people with CPAP-induced CSA, ASV may slightly reduce central AHI compared to bilevel ventilation and to CPAP. In the absence of data showing a favourable impact on meaningful patient-centred outcomes and defining clinically important differences in outcomes in CSA patients, these findings need to be interpreted with caution. Considering the level of certainty of the available evidence and the heterogeneity of participants with CSA, we could draw no definitive conclusions, and further high-quality trials focusing on patient-centred outcomes, such as quality of life, quality of sleep, and longer-term survival, are needed to determine whether one mode of NIPV is better than another or than best supportive care for any particular CSA patient group.

Economic evaluation of CPAP therapy for obstructive sleep apnea: a scoping review and evidence map.

PURPOSE: To synthesize findings of economic evaluations investigating cost-effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) and of strategies of organization of care related to CPAP therapy. METHODS: Scoping review with searches conducted in MEDLINE, CRD, LILACS, and Embase in August 2020. Eligible studies were economic evaluations comparing CPAP to other alternative or assessing strategies of care for CPAP therapy. Results were presented narratively, and incremental cost-effectiveness ratios (ICER) were presented in evidence maps. RESULTS: Of 34 studies, 3 concluded that CPAP is less costly and more effective when compared to usual care. Most studies indicated that CPAP is associated with better health outcomes, but at higher prices. ICER ranged from USD 316 to 98,793 per quality-adjusted life years (QALY) gained (median 16,499; IQR 8267 to 33,119). One study concluded that CPAP is more costly and less effective, when treatment is applied to all patients, regardless of disease severity. Variability of ICER was mainly due to definition of population and applied time horizons. When CPAP was compared to mandibular advancement device, ICER ranged from USD 21,153 to 361,028 (median 89,671; IQR 26,829 to 295,983), which represents the investment in CPAP therapy required to obtain one extra QALY. Three studies assessed the effects of organizing CPAP therapy in primary care, which was cost-effective or cost-saving. CONCLUSIONS: Compared to usual care, CPAP is cost-effective after the second year of treatment, when indicated for moderate-to-severe OSA. CPAP therapy may be even more cost-effective by using different strategies of organization of care. These findings may inform decision making related to CPAP reimbursement in health systems. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

Self-reported versus actigraphy-assessed sleep duration in the ELSA-Brasil study: analysis of the short/long sleep duration reclassification.

PURPOSE: This study was aimed to determine the magnitude and predictors of self-reported short/long sleep duration (SDUR) reclassifications using objective measurements. METHODS: Adult participants from the ELSA-Brasil study performed self-reported SDUR, 7-day wrist actigraphy, and a portable sleep study. We explored two strategies of defining self-reported SDUR reclassification: (1) short and long SDUR defined by <6 and ≥8h, respectively; (2) reclassification using a large spectrum of SDUR categories (<5, 5-6, 7-8, 8-9, and >9 h). RESULTS: Data from 2036 participants were used in the final analysis (43% males; age: 49±8 years). Self-reported SDUR were poorly correlated (r=0.263) and presented a low agreement with actigraphy-based total sleep time. 58% of participants who self-reported short SDUR were reclassified into the reference (6-7.99 h) or long SDUR groups using actigraphy data. 88% of participants that self-reported long SDUR were reclassified into the reference and short SDUR. The variables independently associated with higher likelihood of self-reported short SDUR reclassification included insomnia (3.5-fold), female (2.5-fold), higher sleep efficiency (1.35-fold), lowest O2 saturation (1.07-fold), higher wake after sleep onset (1.08-fold), and the higher number of awakening (1.05-fold). The presence of hypertension was associated with a 3.4-fold higher chance of self-reported long SDUR reclassification. Analysis of five self-reported SDUR categories revealed that the more extreme is the SDUR, the greater the self-reported SDUR reclassification. CONCLUSION: In adults, we observed a significant rate of short/long SDUR reclassifications when comparing self-reported with objective data. These results underscore the need to reappraise subjective data use for future investigations addressing SDUR.

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.

Obstructive sleep apnea is associated with lower adiponectin and higher cholesterol levels independently of traditional factors and other sleep disorders in middle-aged adults: the ELSA-Brasil cohort.

PURPOSE: Obstructive sleep apnea (OSA) may contribute to metabolic and inflammatory deregulation but previous studies failed to consider sleep duration, sleep fragmentation, insomnia, and daytime sleepiness as potential confounders. METHODS: Consecutive non-diabetic middle-aged participants from the ELSA-Brasil cohort were invited to perform a clinical evaluation, home sleep study for 1 night, and wrist actigraphy for 7 days. OSA was defined by an apnea-hypopnea index ≥ 15 events/h. Participants were stratified according to the presence of OSA measuring the following markers: fasting glucose, glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR) index, fasting insulin, insulin after 2 h of glucose load, glycated hemoglobin, total cholesterol and their fractions, triglycerides, C-reactive protein, TNF-alpha, interleukin-6, interleukin-10, leptin, adiponectin, E-selectin, ADMA, MCP-1, TGF, apolipoprotein B, fibrinogen, and lipoprotein(a). Differences between groups were identified by chi-square test and ANOVA. RESULTS: We studied 708 participants (mean age: 46 ± 5 years, men: 44%, BMI 26.1 ± 4.1 kg/m2). Compared to no OSA, participants with OSA presented higher levels while fasting and after 2 h glucose load of insulin, HOMA-IR, cholesterol, triglycerides, and C-reactive protein (all p < 0.001). After linear regression analysis adjusting for traditional risk factors plus sleep duration, fragmentation, insomnia, and daytime sleepiness, OSA was negatively associated with adiponectin (ß = - 0.271 CI 95% - 0.456 - 0.085) and positively associated with cholesterol (ß = 9.707 CI 95% 2.737 16.678). Sex-stratification revealed that these associations were significant for men but not women. CONCLUSIONS: In non-diabetic middle-age adults, men with OSA presented with lower adiponectin and higher cholesterol levels independently of sleep duration, sleep fragmentation, insomnia, and daytime sleepiness.

Impact of CPAP on arterial stiffness in patients with obstructive sleep apnea: a meta-analysis of randomized trials.

PURPOSE: This study aimed to perform a systematic review and meta-analysis of randomized trials investigating the effect of continuous positive airway pressure (CPAP) on non-invasive markers of arterial stiffness in patients with OSA. METHODS: The purpose of the study was to evaluate the effect of CPAP on markers of arterial stiffness (pulse wave velocity (PWV) and augmentation index (Aix)) in patients with OSA. The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically reviewed MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, and LILACS databases for randomized trials (RT) evaluating the changes in markers of arterial stiffness (pulse wave velocity (PWV) and augmentation index (Aix) comparing CPAP vs. controls in patients with OSA. Reviewer Manager version 5.3 (R Foundation for Statistical Computing, Vienna, Austria) was used to perform meta-analysis. Risk of bias analysis was performed using the Cochrane tool. RESULTS: Of the 464 studies initially retrieved, 9 relevant studies with 685 participants were included in the analysis. The studies presented moderate risk of bias. CPAP did not significantly reduce Aix (mean difference, - 1.96 (95% confidence interval (CI) - 5.25 to 1.33), p = 0.24), whereas it significantly changed PWV (mean difference, - 0.44 (95% confidence interval (CI) - 0.76 to - 0.12), p = 0.00). CONCLUSION: CPAP treatment was effective in improving arterial stiffness by reducing PWV in patients with OSA. Additional randomized trials, however, should be performed to confirm these findings.

Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension : A Randomized Clinical Trial.

BACKGROUND: Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain. OBJECTIVE: To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone. DESIGN: Randomized clinical trial. (ClinicalTrials.gov: NCT01784848). SETTING: Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil. PARTICIPANTS: Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m2 were randomly assigned (1:1 ratio). INTERVENTION: RYGB plus MT or MT alone. MEASUREMENTS: The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg). RESULTS: Among 100 patients (76% female; mean BMI, 36.9 kg/m2 [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03]; P < 0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (P < 0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B12 and 2 patients required reoperation. LIMITATION: Single-center, nonblinded trial. CONCLUSION: RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity. PRIMARY FUNDING SOURCE: Ethicon, represented in Brazil by Johnson & Johnson do Brasil.

Bariatric Surgery for Resistant Hypertension: Working in Progress!

PURPOSE OF REVIEW: To discuss the recent evidence pointing the benefits of the bariatric surgery on blood pressure control in patients with obesity and hypertension. Particular focus is devoted to discuss the potential impact on resistant hypertension. RECENT FINDINGS: Growing evidence suggest that bariatric surgery promotes not only a significant reduction in the anti-hypertensive medication while maintained blood pressure control but also a significant proportion of hypertension remission as compared to the usual care. In a sub-analysis of the GATEWAY trial using both office and 24-h ambulatory blood pressure monitoring, the prevalence of resistant hypertension significantly decreased after 12 months in the surgical group whereas the numbers remained stable in the control group. Despite the lack of robust evidence, preliminary findings underscore the strong need to explore the potential role of bariatric surgery on resistant hypertension in patients with obesity. This statement is justified not only for the burden of obesity in this scenario but also for the unmet demands in managing resistant hypertension appropriately by multiple drug-therapy or the lack of real utility of procedures like renal denervation and carotid baroreflex activation.

What Is the Most Common Cause of Secondary Hypertension?: An Interdisciplinary Discussion.

PURPOSE OF REVIEW: Traditional statements in medical textbooks pointed that 90 to 95% of cases of hypertension is essential or primary. However, secondary hypertension seems to be common in those patients with resistant forms of hypertension. Appropriate investigation and treatment may have prognostic impact but frequently hypertension remission did not occur raising concerns about the real meaning of secondary hypertension. Here, we provided an interdisciplinary and critical discussion comprising an endocrinologist, a nephrologist, and a cardiologist with expertise in resistant hypertension. We reviewed the literature approaching each one of the recognizable cause of hypertension. RECENT FINDINGS: Recent studies pointed that the most common causes of secondary hypertension are those who overall responses to their treatments do not promote hypertension remission including obstructive sleep apnea (OSA), chronic kidney disease, renovascular hypertension and primary aldosteronism. The authors raised concerns regarding the lack of inclusion of obesity by several societies as a formal cause of hypertension considering not only the biologic plausibility but also the huge impact of weight loss therapies such as bariatric surgery on hypertension remission. In contrast, there is no discussion that a very rare condition-namely pheochromocytoma-is the most "typical" cause of hypertension by promoting hypertension remission in the majority of patients after surgical procedure. Hypertension is a complex condition with multiple environmental and genetics interactions. In clinical practice, it is challenging to prove causality in hypertension. Common conditions largely acceptable as causes of hypertension (OSA, chronic kidney disease, renovascular hypertension, and primary aldosteronism) frequently occur in a setting of an established hypertension background and therefore do not promote hypertension remission in a significant proportion of patients. If obesity becomes largely accepted by several societies as a secondary form of hypertension, this pandemic condition will be certainly the most common cause of hypertension.