LUCIANO FERREIRA DRAGER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/63, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/63, Hospital das Clínicas, Faculdade de Medicina - Líder
46 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 46
- Effects of continuous positive airway pressure on depression and anxiety symptoms in patients with obstructive sleep apnoea: results from the sleep apnoea cardiovascular Endpoint randomised trial and meta-analysis(2019) ZHENG, Danni; XU, Ying; YOU, Shoujiang; HACKETT, Maree L.; WOODMAN, Richard J.; LI, Qiang; WOODWARD, Mark; LOFFLER, Kelly A.; RODGERS, Anthony; DRAGER, Luciano F.; LORENZI-FILHO, Geraldo; WANG, Xia; QUAN, Wei Wei; TRIPATHI, Manjari; MEDIANO, Olga; OU, Qiong; CHEN, Rui; LIU, Zhihong; ZHANG, Xilong; LUO, Yuanming; MCARDLE, Nigel; MUKHERJEE, Sutapa; MCEVOY, R. Douglas; ANDERSON, Craig S.Background: Whether continuous positive airway pressure (CPAP) treatment can improve depression or anxiety symptoms in obstructive sleep apnoea (OSA) patients remains uncertain. Methods: 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. Findings: 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. Interpretation: CPAP reduces depression symptoms in patients with co-existing OSA and CVD independently of improvements in sleepiness. (C) 2019 Published by Elsevier Ltd.
- Obstructive Sleep Apnea A Cardiometabolic Risk in Obesity and the Metabolic Syndrome(2013) DRAGER, Luciano F.; TOGEIRO, Sonia M.; POLOTSKY, Vsevolod Y.; LORENZI-FILHO, GeraldoObstructive sleep apnea (OSA) is an underdiagnosed condition characterized by recurrent episodes of obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia during sleep. Obesity predisposes to OSA, and the prevalence of OSA is increasing worldwide because of the ongoing epidemic of obesity. Recent evidence has shown that surrogate markers of cardiovascular risk, including sympathetic activation, systemic inflammation, and endothelial dysfunction, are significantly increased in obese patients with OSA versus those without OSA, suggesting that OSA is not simply an epiphenomenon of obesity. Moreover, findings from animal models and patients with OSA show that intermittent hypoxia exacerbates the metabolic dysfunction of obesity, augmenting insulin resistance and nonalcoholic fatty liver disease. In patients with the metabolic syndrome, the prevalence of moderate to severe OSA is very high (similar to 60%). In this population, OSA is independently associated with increased glucose and triglyceride levels as well as markers of inflammation, arterial stiffness, and atherosclerosis. A recent randomized, controlled, crossover study showed that effective treatment of OSA with continuous positive airway pressure for 3 months significantly reduced several components of the metabolic syndrome, including blood pressure, triglyceride levels, and visceral fat. Finally, several cohort studies have consistently shown that OSA is associated with increased cardiovascular mortality, independent of obesity. Taken together, these results support the concept that OSA exacerbates the cardiometabolic risk attributed to obesity and the metabolic syndrome. Recognition and treatment of OSA may decrease the cardiovascular risk in obese patients. (C) 2013 by the American College of Cardiology Foundation
- Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea(2012) DRAGER, Luciano F.; LI, Jianguo; SHIN, Mi-Kyung; REINKE, Christian; AGGARWAL, Neil R.; JUN, Jonathan C.; BEVANS-FONTI, Shannon; SZTALRYD, Carole; OBYRNE, Sheila M.; KROUPA, Olessia; OLIVECRONA, Gunilla; BLANER, William S.; POLOTSKY, Vsevolod Y.Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO2 was decreased to 6.5 once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a 5-fold decrease in LpL activity (P 0.01) and an 80 increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.
- Update in Sleep-disordered Breathing 2016(2017) AYAS, Najib T.; DRAGER, Luciano F.; MORRELL, Mary J.; POLOTSKY, Vsevolod Y.
- Effect of Continuous Positive Airway Pressure on Weight and Local Adiposity in Adults with Obstructive Sleep Apnea A Meta-Analysis(2021) CHEN, Baixin; DRAGER, Luciano F.; PEKER, Yuksel; VGONTZAS, Alexandros N.; PHILLIPS, Craig L.; HOYOS, Camilla M.; SALLES, Gil F.; GUO, Miaolan; LI, YunRationale: Evidence suggests that continuous positive airway pressure (CPAP) treatment promotes weight gain in patients with obstructive sleep apnea (OSA). It is unclear whether weight gain is influenced by CPAP adherence or comorbid disorders. Objectives: To examine the CPAP effects on body mass index (BMI) and local adiposity and the potential moderators of CPAP effects on BMI in patients with OSA. Methods: We searched PubMed/Medline, Embase, and Cochrane through December 2019. Randomized controlled trials of CPAP versus control treatment with >4 weeks' treatment were included. Results: A total of 39 randomized controlled trials with 6,954 subjects were included. In intention-to-treat analysis, the BMI increased significantly after CPAP treatment compared with control treatment (weighted mean difference [WMD], 0.148 kg/m(2); 95% confidence interval, 0.04-0.26; P = 0.001). In studies demonstrating an increase in the BMI, waist and neck circumferences were also significantly increased. Subgroup analyses revealed that an increased BMI was attributable to CPAP use of <5 h/night (WMD, 0.231) but was not attributable to CPAP use of.5 h/night (WMD, 0.001; between-group P value = 0.049). Furthermore, the BMI increased significantly in patients without cardiovascular disease (CVD; WMD, 0.200), whereas it decreased significantly in those with CVD at baseline (WMD, 20.188; between-group P value, 0.001). Moreover, the BMI increased significantly in patients with dysglycemia (WMD, 0.499) but did not increase in those without dysglycemia at baseline (WMD, 0.100; between-group P value = 0.032). Meta-regression confirmed the subgroup findings. Conclusions: The BMI increased significantly in patients with OSA after CPAP treatment, especially in those with CPAP use of <5 h/night, without CVD and/or with dysglycemia at baseline. CPAP use of at least 5 h/night seems to be necessary in mitigating the risk for weight gain in patients with OSA.
- Adherence with positive airway pressure therapy for obstructive sleep apnea in developing vs. developed countries: a big data study(2021) DRAGER, Luciano F.; MALHOTRA, Atul; YAN, Yang; PEPIN, Jean-Louis; ARMITSTEAD, Jeff P.; WOEHRLE, Holger; NUNEZ, Carlos M.; CISTULLI, Peter A.; V, Adam BenjafieldStudy Objectives: Minimal focus has been placed on variations in health care delivery for obstructive sleep apnea (OSA). This study compared positive airway pressure usage in developing countries (Brazil and Mexico) vs. a developed country (United States) and investigated the impact of a patient engagement tool (myAir; ResMed, San Diego, CA) on adherence. Methods: Deidentified data from the AirView database (ResMed) for patients receiving positive airway pressure therapy with wirelessly connected Air10 (AirSense and AirCurve) devices in Brazil, Mexico, and the United States were analyzed. Adherence was defined using US Center for Medicare and Medicaid Services (CMS) criteria (usage >= 4 h/night on >= 70% of nights in the first 90 days). Results: The analysis included 4,181,490 patients (Brazil: 31,672; Mexico 16,934; United States: 4,132,884). CMS adherence over 90 days was slightly lower in Latin America vs. the United States (Brazil: 71.7%; Mexico: 66.4%; United States: 74.0%). Significantly fewer patients were using the patient engagement tool in Brazil (8.1%) and Mexico (2.8%) vs. the United States (26%; both P < .001). Patients registered to use an engagement tool had a higher rate of CMS adherence and were twice as likely to achieve CMS adherence. Average daily usage and days with usage > 4 hours in the first week were the strongest predictors of CMS adherence. Across all countries, > 80% of patients meeting CMS criteria at 3 months were still using positive airway pressure therapy at 1 year, with 1-year adherences rates of > 75%. Conclusions: Short-term and long-term positive airway pressure adherence rates in Brazil and Mexico were similar to those achieved in the United States. Patients who registered to use an engagement tool consistently had better adherence than those who did not.
conferenceObject Adherence with PAP Therapy in Latin America: Results from a Big Data Analysis(2019) DRAGER, L. F.; PEPIN, J.; CISTULLI, P. A.; WOEHRLE, H.; MALHOTRA, A.; NUNEZ, C.; ARMITSTEAD, J. P.; BENJAFIELD, A.- Incident Coronary Calcium Score in Patients With OSA With and Without Excessive Sleepiness Brazilian Longitudinal Study of Adult Health(2024) MIRANDA, Erique Jose Farias Peixoto de; MAZZOTTI, Diego R.; SANTOS, Ronaldo B.; SOUZA, Silvana P.; PARISE, Barbara K.; GIATTI, Soraya; AIELO, Aline N.; CUNHA, Lorenna F.; SILVA, Wagner A.; BORTOLOTTO, Luiz A.; LORENZI-FILHO, Geraldo; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BITTENCOURT, Marcio S.; DRAGER, Luciano F.BACKGROUND: Uncertainty exists about the impact of OSA and its phenotypes on cardio-vascular disease. RESEARCH QUESTION: Are OSA and clinical features such as daytime sleepiness associated with incident subclinical coronary atherosclerosis? STUDY DESIGN AND METHODS: In this prospective community-based cohort study, we administered a sleepiness questionnaire, actigraphy, and home sleep studies at baseline. Coronary artery calcium (CAC; 64-slice multidetector CT scan imaging) was measured at two different time points throughout the study (baseline, between 2010 and 2014, and follow-up, between 2016 and 2018). Incidence of subclinical atherosclerosis was defined as baseline CAC of 0 followed by CAC of > 0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression. Stratified analyses based on excessive daytime sleepiness (EDS) were performed. RESULTS: We analyzed 1,956 participants with available CAC scores at baseline (mean age, 49 +/- 8 years; 57.9% female; 32.4% with OSA). In covariate-adjusted analyses (n = 1,247; mean follow-up, 5.1 +/- 0.9 years), we found a significant association between OSA and incidence of subclinical atherosclerosis (OR, 1.26; 95% CI, 1.06-1.48), with stronger effects among those reporting EDS (OR, 1.66; 95% CI, 1.30-2.12; P = .028 for interaction). Interestingly, EDS per se was not associated with any CAC outcome. An exploratory analysis of the square root of CAC progression (baseline CAC > 0 followed by a numerical increase in scores at follow-up; n = 319) showed a positive association for both OSA (beta = 1.084; 95% CI, 0.032-2.136; P = .043) and OSA with EDS (beta = 1.651; 95% CI, 0.208-3.094; P = .025). INTERPRETATION: OSA, particularly with EDS, predicts the incidence and progression of CAC. These results support biological plausibility for the increased cardiovascular risk observed among patients with OSA with excessive sleepiness.
- Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells(2016) ZYCHOWSKI, Katherine E.; SANCHEZ, Bethany; PEDROSA, Rodrigo P.; LORENZI-FILHO, Geraldo; DRAGER, Luciano F.; POLOTSKY, Vsevolod Y.; CAMPEN, Matthew J.Background and aims: Obstructive sleep apnea (OSA) is characterized by intermittent airway obstruction and systemic hypoxia during sleep, which can contribute to an increase in reactive oxygen species, vascular remodeling, vasoconstriction and ultimately cardiovascular disease. Continuous positive airway pressure (CPAP) is a clinical therapy that maintains airway patency and mitigates several symptoms of OSA. However, it is currently unknown whether CPAP therapy also reduces the overall inflammatory potential in the circulation; to address this in an unbiased manner, we applied a novel endothelial biosensor approach, the serum cumulative inflammatory potential (SCIP) assay. Methods: We studied healthy controls (n = 7), OSA subjects receiving no treatment, (OSA controls) (n = 7) and OSA subjects receiving CPAP for 3 months (n = 8). Serum was obtained from OSA subjects before and after CPAP or no treatment. A battery of quantitative and functional assays was performed to assess the serum inflammatory potential, in terms of endothelial responses. For the SCIP assay, human coronary artery endothelial cells (hCAECs) were incubated with 5% serum in media from individual subjects for 4 h. qPCR was performed to assess endothelial inflammatory transcript (ICAM-1, VCAM-1, IL-8, P-selectin, CCL5, and CXCL12) responses to serum. Additionally, transendothelial resistance was measured in serum-incubated hCAECs following leukocyte challenge. Results: hCAECs exhibited significant increases in VCAM-1, ICAM-1, IL-8 and P-selectin mRNA when incubated with serum from OSA patients compared to serum from healthy control subjects. Furthermore, compared to no treatment, serum from CPAP-treated individuals was less potent at inducing inflammatory gene expression in the SCIP assay. Similarly, in a leukocyte adhesion assay, naive cells treated with serum from patients who received CPAP exhibited improved endothelial barrier function than cells treated with OSA control serum. Conclusions: OSA results in greater serum inflammatory potential, thereby driving endothelial activation and dysfunction.
- Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism(2021) RASSI-CRUZ, Marcela; MARIA, Andrea G.; FAUCZ, Fabio R.; LONDON, Edra; VILELA, Leticia A. P.; SANTANA, Lucas S.; BENEDETTI, Anna Flavia F.; GOLDBAUM, Tatiana S.; TANNO, Fabio Y.; SROUGI, Vitor; CHAMBO, Jose L.; PEREIRA, Maria Adelaide A.; CAVALCANTE, Aline C. B. S.; CARNEVALE, Francisco C.; PILAN, Bruna; BORTOLOTTO, Luiz A.; DRAGER, Luciano F.; LERARIO, Antonio M.; LATRONICO, Ana Claudia; V, Maria Candida B. Fragoso; MENDONCA, Berenice B.; ZERBINI, Maria Claudia N.; STRATAKIS, Constantine A.; ALMEIDA, Madson Q.Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, 'sporadic' bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of gene tic etiologies of PA.