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
20 resultados
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- 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
conferenceObject Acute Effects Of Continous Positive Airway Pressure (cpap) in Hemodynamics And Cardiac Performance In Patients With Hypertrophic Cardiomyopathy(2013) NERBASS, F. B.; PEDROSA, R. P.; FERREIRA FILHO, J. A.; SALEMI, V. M. C.; ARTEAGA-FERNANDEZ, E.; DRAGER, L. F.; LORENZI-FILHO, G.conferenceObject Obstructive Sleep Apnea In The Spectrum Of Coronary Artery Disease: Stable Versus Refractory Angina Patients(2013) GEOVANINI, G. R.; DANZI-SOARES, N.; DOURADO, L. O. C.; POPPI, N. T.; PEREIRA, A. C.; GOWDAK, L. W.; DRAGER, L. F.; LORENZI-FILHO, G.- Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy(2013) NERBASS, Flavia B.; PEDROSA, Rodrigo P.; GENTA, Pedro R.; ANTUNES, Murillo O.; ARTEAGA-FERNANDEZ, Edmundo; DRAGER, Luciano F.; LORENZI-FILHO, GeraldoOBJECTIVE: Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46 +/- 15 years; body mass index, 26.6 +/- 4.9 kg/m(2)) were included, and obstructive sleep apnea (respiratory disturbance index >= 15 events/h) was present in 37 patients (41%). RESULTS: Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age >= 45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47-13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43-20.12; p = 0.013]. CONCLUSION: Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation.
- Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues(2013) YAO, Qiaoling; SHIN, Mi-Kyung; JUN, Jonathan C.; HERNANDEZ, Karen L.; AGGARWAL, Neil R.; MOCK, Jason R.; GAY, Jason; DRAGER, Luciano F.; POLOTSKY, Vsevolod Y.Chronic intermittent hypoxia (CIH) inhibits plasma lipoprotein clearance and adipose lipoprotein lipase (LPL) activity in association with upregulation of an LPL inhibitor angiopoietin-like protein 4 (Angptl4). We hypothesize that CIH inhibits triglyceride (TG) uptake via Angptl4 and that an anti-Angptl4-neutralizing antibody would abolish the effects of CIH. Male C57BL/6J mice were exposed to four weeks of CIH or intermittent air (IA) while treated with Ab (30 mg/kg ip once a week). TG clearance was assessed by [H-3]triolein administration retroorbitally. CIH delayed TG clearance and suppressed TG uptake and LPL activity in all white adipose tissue depots, brown adipose tissue, and lungs, whereas heart, liver, and spleen were not affected. CD146+ CD11b- pulmonary microvascular endothelial cells were responsible for TG uptake in the lungs and its inhibition by CIH. Antibody to Angptl4 decreased plasma TG levels and increased TG clearance and uptake into adipose tissue and lungs in both control and CIH mice to a similar extent, but did not reverse the effects of CIH. The antibody reversed the effects of CIH on LPL in adipose tissue and lungs. In conclusion, CIH inactivates LPL by upregulating Angptl4, but inhibition of TG uptake occurs predominantly via an Angptl4/LPL-independent mechanism.-Yao, Q., M.-K. Shin, J. C. Jun, K. L. Hernandez, N. R. Aggarwal, J. R. Mock, J. Gay, L. F. Drager, and V. Y. Polotsky. Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues. J. Lipid Res. 2013. 54: 1058-1065.
conferenceObject Hypertriglyceridemia Induced By Chronic Intermittent Hypoxia Is Mediated By Hypoxia Inducible Factor (hif-1)(2013) YAO, Q.; DRAGER, L. F.; SHIN, M. -K.; JUN, J. C.; HALBERG, N.; SCHERER, P. E.; SEMENZA, G. L.; POLOTSKY, V. Y.conferenceObject Exercise training and hypocaloric diet improves sympathetic arterial baroreflex control in patients with metabolic syndrome and obstructive sleep apnea(2013) TOSCHI-DIAS, Edgar; TROMBETTA, Ivani C.; SILVA, Valdo J. D.; MAKI-NUNES, Cristiane; CEPEDA, Felipe X.; ALVES, Maria Janieire N. N.; CARVALHO, Glauce; DRAGER, Luciano; LORENZI-FILHO, Geraldo; NEGRAO, Carlos E.; RONDON, Maria Urbana P. B.Metabolic syndrome (MetS) decreases arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA). And, the obstructive sleep apnea (OSA) exacerbates this autonomic dysfunction. We tested the hypothesis that exercise training and hypocaloric diet (ET+D) would restore ABRMSNA in patients with MetS and OSA. Forty-four MetS patients were allocated into four groups: Sedentary with OSA (MetS+OSA Sed, n=10) or without OSA (MetS-OSA Sed, n=10), and ET+D with OSA (MetS+OSA ET+D, n=11) or without OSA (MetS-OSA ET+D, n=13). The ET+D groups were submitted to –500 kcal/day and 40 min bicycle exercise for 4-months. OSA was deferred as apnea-hypopnea index>15 events/hour. MSNA (microneurography), blood pressure (beat-to-beat, noninvasive) and spontaneous ABRMSNA (gain, sensitivity and time delay, latency) were evaluated. ET+D decreased MSNA (P<0.05) and increased ABRMSNA gain in both MetS+OSA (13±1 vs. 24±2 ms/mmHg, P=0.01) and MetS-OSA (27±3 vs. 37±3ms/mmHg, P=0.03) groups. The time delay of ABRMSNA was reduced by ET+D only in MetS+OSA group (4.1±0.2 vs. 2.8±0.3 s, P=0.04). No changes were observed in the sedentary groups. In conclusion, the ET+D improve ABRMSNA sensitivity in patients with MetS regardless of OSA. However, this effect of ET+D is more pronounced in patients with MetS+OSA.- The impact of metabolic syndrome on metabolic, proinflammatory and prothrombotic markers according to the presence of high blood pressure criterion(2013) GIL, Juliana S.; DRAGER, Luciano F.; GUERRA-RICCIO, Grazia M.; MOSTARDA, Cristiano; IRIGOYEN, Maria C.; COSTA-HONG, Valeria; BORTOLOTTO, Luiz A.; EGAN, Brent M.; LOPES, Heno F.OBJECTIVES: We explored whether high blood pressure is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome. METHODS: We evaluated 135 consecutive overweight/obese patients. From this group, we selected 75 patients who were not under the regular use of medications for metabolic syndrome as defined by the current Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults criteria. The patients were divided into metabolic syndrome with and without high blood pressure criteria (>= 130/>= 85 mmHg). RESULTS: Compared to the 45 metabolic syndrome patients without high blood pressure, the 30 patients with metabolic syndrome and high blood pressure had significantly higher glucose, insulin, homeostasis model assessment insulin resistance index, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, uric acid and creatinine values; in contrast, these patients had significantly lower high-density lipoprotein-cholesterol values. Metabolic syndrome patients with high blood pressure also had significantly higher levels of retinol-binding protein 4, plasminogen activator inhibitor 1, interleukin 6 and monocyte chemoattractant protein 1 and lower levels of adiponectin. Moreover, patients with metabolic syndrome and high blood pressure had increased surrogate markers of sympathetic activity and decreased baroreflex sensitivity. Logistic regression analysis showed that high-density lipoprotein, retinol-binding protein 4 and plasminogen activator inhibitor-1 levels were independently associated with metabolic syndrome patients with high blood pressure. There is a strong trend for an independent association between metabolic syndrome patients with high blood pressure and glucose levels. CONCLUSIONS: High blood pressure, which may be related to the autonomic dysfunction, is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome.
- Arousals Are Frequent and Associated With Exacerbated Blood Pressure Response in Patients With Primary Hypertension(2013) GARCIA, Carlos E. V.; DRAGER, Luciano F.; KRIEGER, Eduardo M.; NEGRAO, Carlos E.; BORTOLOTTO, Luiz A.; LORENZI-FILHO, Geraldo; UENO, Linda M.BACKGROUND Spontaneous arousals are relatively common during sleep, and induce hemodynamic responses. We sought to investigate the frequency and magnitude of blood pressure (BP) increases triggered by spontaneous arousals in patients with primary hypertension. METHODS We conducted a study in which we divided 18 nonobese, sedentary adults without sleep-disordered breathing into two groups, consisting of: (i) hypertensive (HT, n = 8) patients; and (ii) normotensive (NT, n = 10) controls. The groups were matched for age and body mass index. All subjects underwent full polysomnography with simultaneous monitoring of heart rate (HR) and beat-by-beat BR Each subject's BP and HR were analyzed immediately before BP peaks triggered by spontaneous arousals during stage 2 of nonrapid eye movement sleep. RESULTS The total sleep time, sleep efficiency, and sleep structure in the two study groups were similar. In contrast, the number of arousals was significantly higher in the HT than in the NT group, at 25 +/- 5 vs. 12 +/- 3 events/h, respectively (P < 0.05). The HR of the HT and NT groups was similar before arousal (65 +/- 3 bpm vs. 67 +/- 3 bpm, respectively, P < 0.01) and increased significantly and similarly in the two groups upon arousal (to 79 +/- 6 bpm vs. 74 +/- 4 bpm, respectively, P < 0.01). Systolic and diastolic BPs were significantly higher throughout sleep in the HT than in the NT group. During spontaneous arousals, BP increased in both groups (P < 0.05). However, the magnitude of the increase in systolic BP was significantly greater in the HT than in the NT group (22 +/- 3 mm Hg vs. 15 +/- 3 mm Hg, P < 0.05). CONCLUSIONS Patients with hypertension who do not have sleep-disordered breathing have an increased cardiovascular burden during sleep, which may be due to the greater number of arousals and exacerbated systolic BP response that they experience during sleep. These novel findings may have cardiovascular implications in patients with hypertension.
- Obstructive Sleep Apnea is Associated with Increased Chemoreflex Sensitivity in Patients with Metabolic Syndrome(2013) TROMBETTA, Ivani C.; MAKI-NUNES, Cristiane; TOSCHI-DIAS, Edgar; ALVES, Maria-Janieire N. N.; RONDON, Maria Urbana P. B.; CEPEDA, Felipe X.; DRAGER, Luciano F.; BRAGA, Ana Maria F. W.; LORENZI-FILHO, Geraldo; NEGRAO, Carlos E.Study Objectives: Obstructive sleep apnea (OSA) is often observed in patients with metabolic syndrome (MetS). In addition, the association of MetS and OSA substantially increases sympathetic nerve activity. However, the mechanisms involved in sympathetic hyperactivation in patients with MetS + OSA remain to be clarified. We tested the hypothesis that chemoreflex sensitivity is heightened in patients with MetS and OSA. Design: Prospective clinical study. Participants: Forty-six patients in whom MetS was newly diagnosed (ATP-III) were allocated into: (1) MetS + OSA (n = 24, 48 +/- 1.8 yr); and (2) MetS -OSA (n = 22, 44 +/- 1.7 yr). Eleven normal control subjects were also studied (C, 47 +/- 2.3 yr). Measurements: OSA was defined as an apnea-hypopnea index >= 15 events/hr (polysomnography). Muscle sympathetic nerve activity (MSNA) was measured by microneurography technique. Peripheral chemoreflex sensitivity was assessed by inhalation of 10% oxygen and 90% nitrogen (carbon dioxide titrated), and central chemoreflex sensitivity by 7% carbon dioxide and 93% oxygen. Results: Physical characteristics and MetS measures were similar between MetS + OSA and MetS - OSA. MSNA was higher in MetS + OSA patients compared with MetS - OSA and C (33 +/- 1.3 versus 28 +/- 1.2 and 18 +/- 2.2 bursts/min, P < 0.05). Isocapnic hypoxia caused a greater increase in MSNA in MetS + OSA than MetS -OSA and C (P = 0.03). MSNA in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.005). Further analysis showed a significant association between baseline MSNA and peripheral (P < 0.01) and central (P < 0.01) chemoreflex sensitivity. Min ventilation in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.001). Conclusion: OSA increases sympathetic peripheral and central chemoreflex response in patients with MetS, which seems to explain, at least in part, the increase in sympathetic nerve activity in these patients. In addition, OSA increases ventilatory central chemoreflex response in patients with MetS.