CARLOS ALEXANDRE WAINROBER SEGRE
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
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conferenceObject Influence of the concentration and molecular composition on the LDL and HDL functional characteristics in patients with the metabolic syndrome(2012) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; CASELLA, Lia B.; DENARDI, Celise; DOURADO, Paulo; SEGRE, Alexandre; ROEVER-BORGES, Leonardo; NEGRAO, Carlos Eduardo; MARANHAO, Raul; CHAGAS, Antonio CarlosIntroduction: Long-term exercise associated with diet changes lipoproteins plasma levels. Objectives: We sought to analize the effects of short-term exercise training without any specific diet (T) on the concentration,composition and functional characteristics of LDL and HDL in patients with metabolic syndrome (MS). Methods: Forty sedentary persons were studied,30 with MS and 10 controls.Twenty of those with MS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer.LDL and HDL subfractions were obtained by plasma ultracentrifugation 1 and their compositions were analyzed. LDL from control subjects was incubated with HDL2a,HDL3b from the MS patients (before and after T) and the in vitro resistance to oxidation was verified. An artificial lipoprotein emulsion (LDE) labeled with 14C-phospholipid, 3 H-triglycerides, 14 C-cholesterol and 3 H-cholesteryl ester was incubated with plasma from the participants. After precipitation of VLDL, LDL and LDE the HDL-containing supernatant was counted for radioactivity to verify the HDL ability to accept lipids. 2 Results: T decreased triglycerides (TG) but did not change apoB,apoA-I,LDL-C and HDL-C plasma levels. LDL resistance to oxidation increased (+91%) after T,associated with a decrease in the LDL content of apoB (-16%) and TG (-14%) and in the concentration of the small and dense LDL particles. Oxidizability of control LDL decreased when mixed with HDL2a or 3b from patients with MS, before vs. after T (-23% for HDL2a and -18% for HDL3b),associated with an increase in PON1 activity in the MS group (58.3±36.2 before vs.70.7±38.4ng/ml/min after T, p<0.05) and with a significant decrease in the content of total cholesterol (TC) and TG in HDL3b and HDL3c but with an increase in cholesterol ester (CE) in HDL3b. T did not significantly modify concentrations of TC and TG in HDL2a, 2b and 3a. Phospholipids and total protein content did not change in all HDL subfractions.T significantly increased free cholesterol and CE transfer from LDE to HDL in MS group to levels similar to those observed in controls. Conclusion: In patients with the MS, T influences the LDL and HDL functionality by earlier changes in molecular composition rather than their concentration, emphasizing the early benefits of exercise and highlighting the importance of evaluating the functional aspects of the lipoproteins besides their plasma levelsconferenceObject Five year follow-up of on-pump versus off pump coronary artery bypass surgery in elderly patients - the MASS III trial(2012) MELO, R. M. Vieira De; REZENDE, P. C.; GARZILLO, C. L.; LIMA, E. G.; SEGRE, C. A. W.; COSTA, L. M. A.; OIKAWA, F. T.; HUEB, W.; RAMIRES, J. A. F.; KALIL FILHO, R.Purpose: Advanced age is associated with increased mortality and morbidity in patients undergoing coronary artery bypass grafting (CABG), which may be a consequence of cardiopulmonary bypass. Thus, off-pump surgery may have an increased benefit in elderly patients. We aim to evaluate cardiac events and long-term clinical outcomes in elderly patients with stable coronary artery disease and preserved left ventricular ejection fraction undergoing off-pump and on-pump CABG. Methods: The MASS III was a single-center randomized trial that evaluate 308 patients with stable coronary artery disease and preserved ventricular function assigned for off-pump (n=155) or on-pump (n=153) CABG. Of this, 176 (58,3%) patients had 60 years or older at the time of randomization (of-pump=90 and on-pump=86). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. Results: The two randomized groups were well-matched for baseline demographic, clinical, and angiographic characteristics. The mean age was 67,2 ( ± 5,0) years. After 5-year follow-up, there were no significant differences between on- pump and off-pump groups in the composite end points: 27,9% vs 21,1% (hazard ratio 1.17, 95% CI 0.87 to 1.59; P=0.29) Figure 1. Six patients (7.0%) died in the on-pump group compared with 10 (11.1%) in the of-pump group (hazard ratio 0.78, 95% CI 0.47 to 1.29; p=0.33). On-pump patients had a higher incidence of postoperative stroke or myocardial infarction: 13 (15.1%) vs 5 (5,6%); p=0,036. Conclusions: Patients undergoing off-pump surgery had a lower incidence of in hospital stroke or myocardial infarction. This finding did not add benefit in clinical outcomes at 5-years follow-up.conferenceObject Role of Hypoglycemic Agents on Ischemic Preconditioning in Diabetic Patients with Stable Multivessel Coronary Artery Disease(2012) GARCIA, Rosa M.; HUEB, Whady; UCHIDA, Augusto H.; REZENDE, Paulo C.; LIMA, Eduardo G.; GARZILLO, Cibele L.; SEGRE, Carlos A.; FAVARATO, Desiderio; RAMIRES, Jose A.; KALIL FILHO, RobertoconferenceObject LIPID TRANSFER TO HIGH DENSITY LIPOPROTEINS IN TYPE 2 DIABETIC PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE(2012) SPRANDEL, Marilia C. O.; HUEB, Whady; CASELLA-FILHO, Antonio; SEGRE, Alexandre; REZENDE, Paulo Cury; CARVALHO, Ana L. O.; FAVARATO, Desiderio; MARANHAO, Raul C.; RAMIRES, Jose; KALIL-FILHO, RobertoBackground In type 2 diabetes mellitus (DM2), HDL-cholesterol is diminished and it is important to understand the functional and metabolic changes existing in HDL in DM2 patients that may predispose to coronary artery disease (CAD). Lipid transfers between HDL and the other lipoproteins, mediated by cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), are crucial steps in HDL formation and role in reverse cholesterol transfer. Objective Investigate whether development of CAD in DM2 patients are associated with alterations in lipid transfers to HDL and in content of free cholesterol in the plasma. Methods 78 patients with DM2 and CAD (DM2-CAD) and 78 with DM2 without CAD, as diagnosed by cineangiography, were studied. They were of both genders, aged 40-80 yrs. Plasma was incubated for 1h at 37oC with a donor nanoemulsion labeled with 3H -cholesteryl-esters and14C -phospholipids or with 14C-free-cholesterol and 3H -triglycerides. Radioactive lipids transferred from the donor nanoemulsion to HDL were measured in the supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. Results are % of the total radioactivity of each lipid in HDL. Results In DM2-CAD, LDL-cholesterol and triglycerides were higher than in DM2; HDL-cholesterol was lower. Compared to DM2, DM2-CAD showed diminished transfer to HDL of free-cholesterol (DM2-CAD=4.23±0.24; DM2= 5.66±0.14, p<0.0001) and of triglycerides (1.65±0.13 vs 3.08±0.11, p<0.0001), whereas cholesteryl-ester transfer was increased (3.67±0.16 vs 2.25±0.13, p<0.0001); phospholipid transfer was equal (15.37±0.60 vs15.18±0.20, p=0.76). CETP concentration was equal, while plasma free-cholesterol was higher in DM2-CAD (DM2-CAD=36.9±0.9; DM2=33.1±0.7, p=0.003).HDL particle diameter was equal in both groups. Conclusion The reduction of free-cholesterol transfer to HDL may hinder cholesterol esterification and reverse cholesterol transport. Alterations in triglyceride and cholesteryl-ester transfer may affect lipoprotein stability. Those disturbances in HDL metabolism may facilitate CAD development in DM2. ACC Oral Contributions McCormick Place South, S100c Sunday, March 25, 2012, 9:04 a.m.-9:17 a.m. Session Title: Prevention: Focus on Lipids Abstract Category: 9. Prevention: Clinical Presentation Number: 911-8conferenceObject THE TRIGLYCERIDE/HDL RATIO REMAINS AS AN INDEPENDENT PLASMA LIPID MARKER OF MAJOR CARDIOVASCULAR EVENTS IN DIABETIC PATIENTS 10-YEAR FOLLOW-UP FROM THE MEDICINE ANGIOPLASTY OR SURGERY STUDY II (MASS II) TRIAL(2012) CASELLA-FILHO, Antonio; HUEB, Whady; JONKE, Vivian; SANTOS, Raul; FAVARATO, Desiderio; LIMA, Eduardo; SEGRE, Alexandre; REZENDE, Paulo Cury; GARZILLO, Cibele Larrosa; CHACRA, Ana P. M.; RAMIRES, Jose; KALIL-FILHO, RobertoBackground: The second Medical, Angioplasty, or Surgery Study (MASS II) compared the long-term effects of medical treatment (MT), angioplasty (PCI), or surgical strategies (CABG) among patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function who were appropriate candidates for all 3 therapies. Plasma lipids are important risk factors for cardiovascular events in CAD patients, especially in diabetics. We showed previously that the TG/HDL ratio was the only parameter independently associated with major cardiovascular events (MACE; overall death, myocardial infarction, and unstable angina that required myocardial revascularization) in patients after the 10-year follow up of stable CAD patients in the MASS II. In this analysis we evaluated the association of plasma lipids with MACE in diabetic patients after a 10-year follow-up of the MASS II. Methods: The data of 200 patients of the MASS II, 100 diabetics and 100 non diabetics, were analyzed for risk factors and plasma lipids levels. The levels of fasting plasma lipids were determined at baseline and 6 months after randomization. It was instituted in all study patient groups the same lipid therapy. Concentrations of total cholesterol, HDL, non-HDL and LDL-cholesterol as well as LDL/HDL, and TG/HDL ratios were divided according to distribution quartiles. The association of plasma lipids at baseline and at 6 months with MACE was determined by Cox regression models. Results: The patients were followed up for an average of 11.4 years. In the subgroup of diabetic patients, after adjustment for confounders, older age (> 65 years old), randomized treatment for CAD (CABG vs. MT) and the TG/HDL ratio determined at 6 months were independently associated with MACE. There was no association between MACE and other plasma lipids. Conclusions: The TG/HDL remains as a lipid parameter independently associated with MACE in diabetic patients after the 10-year follow up of stable CAD patients in the MASS II.- Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial(2012) HUEB, Whady; GERSH, Bernard J.; REZENDE, Paulo Cury; GARZILLO, Cibele Larrosa; LIMA, Eduardo Gomes; VIEIRA, Ricardo D'Oliveira; GARCIA, Rosa Maria Rahmi; FAVARATO, Desiderio; SEGRE, Carlos Alexandre W.; PEREIRA, Alexandre Costa; SOARES, Paulo Rogerio; RIBEIRO, Expedito; LEMOS, Pedro; PERIN, Marco A.; STRUNZ, Celia Cassaro; DALLAN, Luis A. O.; JATENE, Fabio B.; STOLF, Noedir A. G.; HUEB, Alexandre Ciappina; DIAS, Ricardo; GAIOTTO, Fabio A.; COSTA, Leandro Menezes Alves da; OIKAWA, Fernando Teiichi Costa; MELO, Rodrigo Morel Vieira de; SERRANO JUNIOR, Carlos Vicente; AVILA, Luiz Francisco Rodrigues de; VILLA, Alexandre Volney; PARGA FILHO, Jose Rodrigues; NOMURA, Cesar; RAMIRES, Jose A. F.; KALIL FILHO, RobertoBackground: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. Methods/Design: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. Discussion: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.
conferenceObject Anti-inflammatory properties of HDL after short-term exercise training in patients with metabolic syndrome(2012) CASELLA-FILHO, A.; TROMBETTA, I. C.; CASELLA, L. B.; DOURADO, P. M. M.; SEGRE, A.; FAVARATO, D.; ROEVER-BORGES, L.; NEGRAO, C. E.; MARANHAO, R. C.; CHAGAS, A. C. P.Background: Recent study showed that short-term exercise, associated with diet and weight loss, improves the anti-inflammatory properties of HDL in metabolic syndrome (MS). However, diet and weight loss, per se, can alter the functionality of HDL and, in real life, many patients do not follow the medical counseling of diet and exercise simultaneously. We showed previously that the antioxidative characteristics and the capacity to accept lipids of HDL are early improved by short-term exercise training (Tr) with no diet associated. We sought to verify whether the anti-inflammatory properties of HDL are affected by Tr, without any diet associated, in patients with MS. Methods: Forty sedentary persons (30 with MetS,10 controls) were evaluated. Twenty of those with MS were subjected to a 3 times/week training load (45 min/day) for 3 months on a bicycle. Plasma high-sensitivity C-reactive protein (hs-CRP) was analyzed and HDL sub-fractions were obtained by plasma ultracentrifugation. Endothelial cells were cultured, stimulated with TNF-α and lipopolysacharide, and coincubated with HDL subfractions obtained before and after Tr. Sequentially, those cultures of endothelial cells were coincubated with THP-1 cells labeled with a fluorescent marker. The labeled THP-1 cells that adhered on endothelial cells were counted under fluoroscopic microscope. Results: Baseline plasma levels of HDL-C were lower in the MS group compared to controls and Tr did not change neither HDL-C nor weight in MS group. Hs-CRP plasma levels from patients with MetS were higher than controls (3.0±1.5 vs 1.5±1.5 mg/L respectively, p<0.05) and did not change after Tr(3.0±1.5 vs 2.8±1.8 mg/L, before and after Tr respectively, p>0.05). The number of adhered labeled THP-1 cells coincubated with endothelial cells did not change significantly when mixed with HDL2a or HDL3b from patients with MS after Tr, compared with HDL2a or HDL3b obtained before Tr. Conclusion: Our results showed that Tr did not change an inflammatory serum marker (hs-CRP) and the adherence of THP-1 cells on endothelium cells, suggesting that the anti-inflammatory properties of HDL are not early improved by short-term exercise, when there is no diet associated.