GERALDO LORENZI FILHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/63, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/63, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
Resultados de Busca
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- Predictors of long-term adherence to continuous positive airway pressure in patients with obstructive sleep apnea and cardiovascular disease(2019) RYSWYK, Emer Van; ANDERSON, Craig S.; ANTIC, Nicholas A.; BARBE, Ferran; BITTENCOURT, Lia; FREED, Ruth; HEELEY, Emma; LIU, Zhihong; LOFFLER, Kelly A.; LORENZI-FILHO, Geraldo; LUO, Yuanming; MARGALEF, Maria J. Masdeu; MCEVOY, R. Doug; MEDIANO, Olga; MUKHERJEE, Sutapa; OU, Qiong; WOODMAN, Richard; ZHANG, Xilong; CHAI-COETZER, Ching LiStudy Objectives: Poor adherence to continuous positive airway pressure (CPAP) commonly affects therapeutic response in obstructive sleep apnea (OSA). We aimed to determine predictors of adherence to CPAP among participants of the Sleep Apnea and cardioVascular Endpoints (SAVE) trial. Methods: SAVE was an international, randomized, open trial of CPAP plus usual care versus usual care (UC) alone in participants (45-75 years) with co-occurring moderate-to-severe OSA (>= 12 episodes/h of >= 4% oxygen desaturation) and established cardiovascular (CV) disease. Baseline sociodemographic, health and lifestyle factors, OSA symptoms, and 1-month change in daytime sleepiness, as well as CPAP side effects and adherence (during sham screening, titration week, and in the first month), were entered in univariate linear regression analyses to identify predictors of CPAP adherence at 24 months. Variables with p < 0.2 were assessed for inclusion in a multivariate linear mixed model with country, age, and sex included a priori and site as a random effect. Results: Significant univariate predictors of adherence at 24 months in 1,121 participants included: early adherence measures, improvement in daytime sleepiness at 1 month, fixed CPAP pressure, some measures of OSA severity, cardiovascular disease history, breathing pauses, and very loud snoring. While observed adherence varied between countries, adherence during sham screening, initial titration, and the first month of treatment retained independent predictive value in the multivariate model along with fixed CPAP pressure and very loud snoring. Conclusions: Early CPAP adherence had the greatest predictive value for identifying those at highest risk of non-adherence to long-term CPAP therapy.
conferenceObject CLINICAL AND POLYSOMNOGRAPHIC CHARACTERISTICS OF PATIENTS FROM AN OTORHINOLARYNGOLOGIC RESEARCH SERVICE(2012) FOMIN, D.; PERLA, S.; LORENZI-FILHO, G.; DIAS, I. S.; AGUIAR, I; HIRATA, R. P.; SANTOS, I. R.; OLIVEIRA, L. F.Introduction: Obstructive sleep apnea (OSA) is a respiratory disorder characterized by collapse of the upper airway during sleep. OSA is an independent risk factor for cardiovascular disease, which includes hypertension, atrial fibrillation, coronary artery disease, and stroke, and has important social implications with reduction in quality of life. Our objective is to describe the demographic, clinical and polysomnographic variables of patients from an otorhinolaryngologic service. Methods: This is a descriptive clinical study conducted with patients from an otorhinolaryngologic research service. Patients were evaluated regarding to anthropometric measurements, full overnight polysomnography, Epworth Sleepiness Scale (ESS) and Berlin Questionnaire. Results: Ninety subjects were consecutively evaluated, consisting of 46 men and 44 women, with a mean age of 45.3±15.6 years and a mean BMI of 29.4±5.1kg/m2. Among the main complaints, snoring was the most reported (89%) followed by apnea (40%). Regarding to sleep disorders, the median the score in ESS was 13 (0-25) and 55 (61,1%) subjects were considered high risk to develop OSA by the Berlin Questionnaire. Twenty-two (24.4%) subjects were considered normal (AHI<5), 22 (24.4%) had mild OSA, 20 (22.2%) had moderate OSA and 26 (28%) were considered severe OSA. The mean AHI was 26.3±27.4, the mean arousal index was 18.8±14.2 and the mean oxyhemoglobin saturation was 93.9±4.7%. Conclusion: This population is characterized as young adults and overweight. There was an important prevalence of OSA, being half of them moderate to severe OSA, which could lead to cardiovascular disorders, diurnal excessive sleepiness and consequently reduction in quality of life.- The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress(2015) ANTIC, Nick A.; HEELEY, Emma; ANDERSON, Craig S.; LUO, Yuanming; WANG, Jiguang; NEAL, Bruce; GRUNSTEIN, Ron; BARBE, Ferran; LORENZI-FILHO, Geraldo; HUANG, Shaoguang; REDLINE, Susan; ZHONG, Nanshan; MCEVOY, R. DougThe Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed.
- Obstructive Sleep Apnea Impairs Postexercise Sympathovagal Balance in Patients with Metabolic Syndrome(2015) CEPEDA, Felipe X.; TOSCHI-DIAS, Edgar; MAKI-NUNES, Cristiane; RONDON, Maria Urbana P. B.; ALVES, Maria Janieire N. N.; BRAGA, Ana Maria F. W.; MARTINEZ, Daniel G.; DRAGER, Luciano F.; LORENZI-FILHO, Geraldo; NEGRAO, Carlos E.; TROMBETTA, Ivani C.Study Objectives: The attenuation of heart rate recovery after maximal exercise (Delta HRR) is independently impaired by obstructive sleep apnea (OSA) and metabolic syndrome (MetS). Therefore, we tested the hypotheses: (1) MetS + OSA restrains Delta HRR; and (2) Sympathetic hyperactivation is involved in this impairment. Design: Cross-sectional study. Participants: We studied 60 outpatients in whom MetS had been newly diagnosed (ATP III), divided according to apnea-hypopnea index (AHI) >= 15 events/h in MetS + OSA (n = 30, 49 +/- 1.7 y) and AHI < 15 events/h in MetS - OSA (n = 30, 46 +/- 1.4 y). Normal age-matched healthy control subjects (C) without MetS and OSA were also enrolled (n = 16, 46 +/- 1.7 y). Interventions: Polysomnography, microneurography, cardiopulmonary exercise test. Measurements and Results: We evaluated OSA (AHI - polysomnography), muscle sympathetic nerve activity (MSNA - microneurography) and cardiac autonomic activity (LF = low frequency, HF = high frequency, LF/HF = sympathovagal balance) based on spectral analysis of heart rate (HR) variability. Delta HRR was calculated (peak HR minus HR at first, second, and fourth minute of recovery) after cardiopulmonary exercise test. MetS + OSA had higher MSNA and LF, and lower HF than MetS - OSA and C. Similar impairment occurred in MetS - OSA versus C (interaction, P < 0.01). MetS + OSA had attenuated Delta HRR at first, second, and at fourth minute than did C, and attenuated Delta HRR at fourth minute than did MetS - OSA (interaction, P < 0.001). Compared with C, MetS - OSA had attenuated Delta HRR at second and fourth min (interaction, P < 0.001). Further analysis showed association of the Delta HRR (first, second, and fourth minute) and AHI, MSNA, LF and HF components (P < 0.05 for all associations). Conclusions: The attenuation of heart rate recovery after maximal exercise is impaired to a greater degree where metabolic syndrome (MetS) is associated with moderate to severe obstructive sleep apnea (OSA) than by MetS with no or mild or no OSA. This is at least partly explained by sympathetic hyperactivity.
- Sleep Apnea Cardiovascular Clinical Trials-Current Status and Steps Forward: The International Collaboration of Sleep Apnea Cardiovascular Trialists(2013) GOTTLIEB, Daniel J.; CRAIG, Sonya E.; LORENZI-FILHO, Geraldo; HEELEY, Emma; REDLINE, Susan; MCEVOY, R. Doug; DURAN-CANTOLLA, JoaquinSleep apnea is a common chronic disease that is associated with coronary heart disease, stroke, heart failure and mortality, although the ability of sleep apnea treatment to reduce cardiovascular morbidity and mortality has not been demonstrated. In contrast to patients seeking treatment in sleep disorders centers, as many as half of individuals with moderate to severe sleep apnea in the general population do not report excessive sleepiness; however, if treatment of sleep apnea were shown to reduce cardiovascular disease risk, this would provide a strong rationale for treatment of sleep apnea even in the absence of daytime sleepiness. This article summarizes the status of clinical trials evaluating the potential cardiovascular benefits of sleep apnea treatment and discusses the challenges of conducting such trials, and introduces the International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT), a clinical research collaboration formed to foster cardiovascular sleep research.
- The Extracellular Matrix of the Lateral Pharyngeal Wall in Obstructive Sleep Apnea(2012) DANTAS, Danielle Andrade da Silva; MAUAD, Thais; SILVA, Luiz F. F.; LORENZI-FILHO, Geraldo; FORMIGONI, Gilberto G. S.; CAHALI, Michel B.Study Objectives: To compare the components of the extracellular matrix in the lateral pharyngeal muscular wall in patients with and without obstructive sleep apnea (OSA). This may help to explain the origin of the increased collapsibility of the pharynx in patients with OSA. Design: Specimens from the superior pharyngeal constrictor muscle, obtained during pharyngeal surgeries, were evaluated using histochemical and immunohistochemical analyses to determine the fractional area of collagen types I and II, elastic fibers, versican, fibronectin, and matrix metalloproteinases 1 and 2 in the endomysium. Setting: Academic tertiary center. Patiens: A total of 51 nonobese adult patients, divided into 38 patients with OSA and 13 nonsnoring control subjects without OSA. Interventions: Postintervention study performed on tissues from patients after elective surgery. Measurements and Results: Pharyngeal muscles of patients with OSA had significantly more collagen type I than pharyngeal muscles in control subjects. Collagen type I was correlated positively and independently with age. The other tested components of the extracellular matrix did not differ significantly between groups. In a logistic regression, an additive effect of both the increase of collagen type I and the increase in age with the presence of OSA was observed (odds ratio (OR), 2.06; 95% confidence interval (CI), 1.17-3.63), when compared with the effect of increased age alone (OR, 1.11; 95% CI, 1.03-1.20). Conclusion: Collagen type I in the superior pharyngeal constrictor muscle was more prevalent in patients with OSA and also increased with age. It was hypothesized that this increase could delay contractile-relaxant responses in the superior pharyngeal constrictor muscle at the expiratory-inspiratory phase transition, thus increasing pharyngeal collapsibility.
- 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.
- Increased Muscle Sympathetic Nerve Activity and Impaired Executive Performance Capacity in Obstructive Sleep Apnea(2016) GOYA, Thiago T.; SILVA, Rosyvaldo F.; GUERRA, Renan S.; LIMA, Marta F.; BARBOSA, Eline R. F.; CUNHA, Paulo Jannuzzi; LOBO, Denise M. L.; BUCHPIGUEL, Carlos A.; BUSATTO-FILHO, Geraldo; NEGRAO, Carlos E.; LORENZI-FILHO, Geraldo; UENO-PARDI, Linda M.Study Objectives: To investigate muscle sympathetic nerve activity (MSNA) response and executive performance during mental stress in obstructive sleep apnea (OSA). Methods: Individuals with no other comorbidities (age = 52 +/- 1 y, body mass index = 29 +/- 0.4, kg/m(2)) were divided into two groups: (1) control (n = 15) and (2) untreated OSA (n = 20) defined by polysomnography. Mini-Mental State of Examination (MMSE) and Inteligence quocient (IQ) were assessed. Heart rate (HR), blood pressure (BP), and MSNA (microneurography) were measured at baseline and during 3 min of the Stroop Color Word Test (SCWT). Sustained attention and inhibitory control were assessed by the number of correct answers and errors during SCWT. Results: Control and OSA groups (apnea-hypopnea index, AHI = 8 +/- 1 and 47 +/- 1 events/h, respectively) were similar in age, MMSE, and IQ. Baseline HR and BP were similar and increased similarly during SCWT in control and OSA groups. In contrast, baseline MSNA was higher in OSA compared to controls. Moreover, MSNA significantly increased in the third minute of SCWT in OSA, but remained unchanged in controls (P < 0.05). The number of correct answers was lower and the number of errors was significantly higher during the second and third minutes of SCWT in the OSA group (P < 0.05). There was a significant correlation (P < 0.01) between the number of errors in the third minute of SCWT with AHI (r = 0.59), arousal index (r = 0.55), and minimum O-2 saturation (r = -0.57). Conclusions: As compared to controls, MSNA is increased in patients with OSA at rest, and further significant MSNA increments and worse executive performance are seen during mental stress.
- Upper Airway Collapsibility is Associated with Obesity and Hyoid Position(2014) GENTA, Pedro R.; SCHORR, Fabiola; ECKERT, Danny J.; GEBRIM, Eloisa; KAYAMORI, Fabiane; MORIYA, Henrique T.; MALHOTRA, Atul; LORENZI-FILHO, GeraldoStudy Objectives: Upper airway anatomy plays a major role in obstructive sleep apnea (OSA) pathogenesis. An inferiorly displaced hyoid as measured by the mandibular plane to hyoid distance (MPH) has been consistently associated with OSA. The hyoid is also a common landmark for pharyngeal length, upper airway volume, and tongue base. Tongue dimensions, pharyngeal length, and obesity are associated with OSA severity, although the link between these anatomical variables and pharyngeal collapsibility is less well known. We hypothesized that obesity as measured by body mass index (BMI), neck and waist circumferences, and variables associated with hyoid position (pharyngeal length, upper airway volume, and tongue dimensions) would be associated with passive pharyngeal critical closing pressure (Pcrit). Design: Cross-sectional. Setting: Academic hospital. Patients: 34 Japanese-Brazilian males age 21 to 70 y. Interventions: N/A. Measurements and Results: We performed computed tomography scans of the upper airway, overnight polysomnography, and Pcrit measurements in all subjects. On average, subjects were overweight (BMI = 28 +/- 4 kg/m(2)) and OSA was moderately severe (apnea-hypopnea index = 29 [13-51], range 1-90 events/h). Factor analysis identified two factors among the studied variables: obesity (extracted from BMI, neck and waist circumferences) and hyoid position (MPH, pharyngeal length, tongue length, tongue volume, and upper airway volume). Both obesity and hyoid position correlated with Pcrit (r = 0.470 and 0.630, respectively) (P < 0.01). In addition, tongue volume, tongue length, pharyngeal length, and MPH correlated with waist and neck circumferences (P < 0.05). Conclusions: Pharyngeal critical closing pressure is associated with obesity and hyoid position. Tongue dimensions, pharyngeal length, and the mandibular plane to hyoid distance are associated with obesity variables. These findings provide novel insight into the potential factors mediating upper airway collapse in obstructive sleep apnea.
- Arterial Stiffness: A Long Sleeper Issue?(2011) DRAGER, Luciano F.; LORENZI-FILHO, Geraldo