JOSE EDUARDO KRIEGER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
71 resultados
Resultados de Busca
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- A prospective study of patients with refractory angina: outcomes and the role of high-sensitivity troponin T(2017) POPPI, Nilson T.; GOWDAK, Luis H. W.; DOURADO, Luciana O. C.; ADAM, Eduardo L.; LEITE, Thiago N. P.; MIOTO, Bruno M.; KRIEGER, Jose E.; CESAR, Luiz A. M.; PEREIRA, Alexandre C.BackgroundThe predictors of cardiovascular events in patients with chronic refractory angina are limited. High-sensitivity cardiac troponin T (hs-cTnT) assays are biomarkers that may be used to determine the prognosis of patients with stable coronary artery disease. HypothesisHs-cTnT is a predictor of death and nonfatal myocardial infarction (MI) in patients with refractory angina. MethodsWe prospectively enrolled 117 consecutive patients in this study. A heart team ruled out myocardial revascularization feasibility after assessing recent coronary angiograms; evidence of myocardial ischemia served as an inclusion criterion. Optimal medical therapy was encouraged via outpatient visits every 6 months; plasma hs-cTnT levels were determined at baseline. The primary endpoint was the composite incidence of death and nonfatal MI. ResultsDuring a median follow-up period of 28.0 months (interquartile range, 18.0-47.5 months), an estimated 28.0-month cumulative event rate of 13.4% was determined via the Kaplan-Meier method. Univariate predictors of the composite endpoint were hs-cTnT levels and LV dysfunction. Following a multivariate analysis, only hs-cTnT was independently associated with the events in question, either as a continuous variable (hazard ratio per unit increase in the natural logarithm: 2.83, 95% confidence interval: 1.62-4.92, P < 0.001) or as a categorical variable (hazard ratio for concentrations above the 99th percentile: 5.14, 95% confidence interval: 2.05-12.91, P < 0.001). ConclusionsIn patients with chronic refractory angina, plasma concentration of hs-cTnT is the strongest predictor of death and nonfatal MI. Notably, none of the outcomes in question occurred in patients with baseline plasma levels <5.0 ng/L.
conferenceObject PREDICTORS OF CORONARY ARTERY CALCIFICATION INCIDENCE IN SEVERE HYPERCHOLESTEROLEMIA(2023) MARTE, Ana; MINAME, Marcio Hiroshi; PARDI, Estevao Magalhaes; GANEM, Lucas; MIZUTA, Marjorie Hayashida; ROCHA, Viviane Zorzanelli; PEREIRA, Alexandre Costa; KRIEGER, Jose Eduardo; SANTOS, Raul- Circulating Dipeptidyl Peptidase IV Activity Correlates With Cardiac Dysfunction in Human and Experimental Heart Failure(2013) SANTOS, Leonardo dos; SALLES, Thiago A.; ARRUDA-JUNIOR, Daniel F.; CAMPOS, Luciene C. G.; PEREIRA, Alexandre C.; BARRETO, Ana Luiza T.; ANTONIO, Ednei L.; MANSUR, Alfredo J.; TUCCI, Paulo J. F.; KRIEGER, Jose E.; GIRARDI, Adriana C. C.Background The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated. Methods and Results Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of approximate to 130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (approximate to 50%) and heart tissue (approximate to 3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion. Conclusions Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.
conferenceObject Influence of genetic polymorphisms of alpha-adrenergic receptors, endothelial nitric oxide synthase and bradykinin receptor B2 on treadmill exercise test responses(2012) NUNES, R. A. Belo; BARROSO, L. P.; SCHMIDT, R. T.; BARRETO, D. D.; FREITAS, H. F.; PEREIRA, A. C.; KRIEGER, J. E.; MANSUR, A. J.Purpose: Treadmill exercise testing responses have been associated with cardiovascular prognosis in individuals without overt heart disease. Neurohumoral and nitric oxide responses may influence cardiovascular performance during exercise. The aim of this study was evaluate associations between genetic polymorphisms of alpha-adrenergic receptors (ADRA1A, ADRA2A and ADRA2B), endothelial nitric oxide synthase (eNOS) and bradykin receptor B2 (BK2R) and treadmill exercise test responses in individuals without overt heart disease. Method: We enrolled 766 (417 women and 349 men) asymptomatic subjects. We selected the following variables during a maximal symptom-limited treadmill exercise test: exercise capacity, chronotropic reserve, maximum heart-rate achieved, heart-rate recovery, exercise systolic blood pressure, exercise diastolic blood pressure and systolic blood pressure recovery. Genotypes for the ADRA1A Arg347Cys (rs1048101), ADRA2A C1780T (rs553668), ADRA2B Del 301-303 (rs28365031), eNOS T786C (rs2070744), eNOS Glu298Asp (rs1799983) and BK2R (rs5810761) polymorphisms were assessed by polymerase chain reaction (PCR) followed by high resolution melting analysis. Laboratory and demographic data were collected for all participants. Statistical analysis was performed with multiple regression models for women and men. Results: The genotype frequencies were under Hardy-Weinberg equilibrium, except for the ADRA2B Del301-303 polymorphism. In the multivariated analysis the ADRA2A C1780T polymorphism was significantly associated with exercise diastolic blood pressure in both sexes. Exercise diastolic blood pressure was higher in individuals with TT genotype than in C allel carriers (P=0.003 for women; P=0.007 for men) (Table 1). The other polymorphisms did not influence significantly the treadmill exercise test responses. Conclusion: The ADRA2A C1780T influenced the exercise diastolic blood pressure in both sexes. This finding suggests that this polymorphism may be a marker of blood pressure response during exercise.- Temporal Change of Extracellular Matrix during Vein Arterialization Remodeling in Rats(2019) MIYAKAWA, Ayumi Aurea; BASSANEZE, Vinicius; DUARTE, Nubia Esteban; GIRAO-SILVA, Thais; BIZERRA, Monica Nunes; CAMPOS, Julliana Carvalho; KRIEGER, Jose EduardoThe global expression profile of the arterialized rat jugular vein was established to identify candidate genes and cellular pathways underlying the remodeling process. The arterialized jugular vein was analyzed on days 3 and 28 post-surgery and compared with the normal jugular vein and carotid artery. A gene array platform detected 9846 genes in all samples. A heatmap analysis uncovered patterns of gene expression showing that the arterialized vein underwent a partial transition from vein to artery from day 3 to 28 post-surgery. The same pattern was verified for 1845 key differentially expressed genes by performing a pairwise comparison of the jugular vein with the other groups. Interestingly, hierarchical clustering of 60 genes with altered expression on day 3 and day 28 displayed an expression pattern similar to that of the carotid artery. Enrichment analysis results and the network relationship among genes modulated during vein arterialization showed that collagen might play a role in the early remodeling process. Indeed, the total collagen content was increased, with the augmented expression of collagen I, collagen IV, and collagen V in arterialized veins. Additionally, there was an increase in the expression of versican and Thy-1 and a decrease in the expression of biglycan and beta 1-integrin. Overall, we provide evidence that vein arterialization remodeling is accompanied by consistent patterns of gene expression and that collagen may be an essential element underlying extracellular matrix changes that support the increased vascular wall stress of the new hemodynamic environment.
- Modelo porcino para avaliação e desenvolvimento de diferentes dispositivos coronários baseados em cateter: ferramenta pré-clínica fundamental(2013) GALON, Micheli Zanotti; TAKIMURA, Celso Kiyochi; CHAVES, Márcio J. Figueira; CAMPOS, Julliana Carvalho de; KRIEGER, J. Eduardo; GUTIERREZ, Paulo Sampaio; LAURINDO, Francisco Rafael Martins; KALIL FILHO, Roberto; LEMOS NETO, Pedro AlvesBACKGROUND: The experimental porcine model is anatomically and physiologically similar to the human heart, it is easily reproducible and very useful to test new stent and balloon generations. This study was aimed at analyzing an experimental model to evaluate different coronary devices for percutaneous coronary intervention. METHODS: We evaluated 131 juvenile commercial farm pigs, 109 were female, weighing 26.4 ± 3.2 kg. They were anesthetized and had mechanical ventilation and monitoring. Vascular access was obtained via the femoral artery by dissection or puncture. The coronary device was used after a selective catheterization of the coronary arteries with a JR 6 F catheter. Animals were maintained on mechanical ventilation until recovery and were submitted to angiographic evaluation 7, 28, 90 and/or 180 days after the procedure. After euthanasia, the hearts were collected and submitted to macro and microscopic analysis. RESULTS: Six drug-eluting stents, two drug-eluting balloons and two bare-metal stents were tested. Unplanned deaths were observed in 1.5% of the cases during the procedures and in 9.2% of the cases after the procedure, occurring within 12 hours to 6 days (2.3 ± 1.6 days). In addition to angiographic evaluations, intravascular ultrasound and optical coherence tomography were performed during the procedures in 20% and 60% of the cases, respectively. There was no deaths related to the use of the devices. CONCLUSIONS: The experimental percutaneous porcine model proved to be reproducible with similar outcomes and low mortality for the different devices tested and is an essential tool for the evaluation of new coronary devices.
- Health related quality of life in individuals at high risk for familial hypercholesterolemia undergoing genetic cascade screening in Brazil(2018) SOUTO, Ana Cristina; MINAME, Marcio H.; FUKUSHIMA, Julia; JANNES, Cinthia E.; KRIEGER, Jose E.; HAGGER, Martin; PEREIRA, Alexandre C.; SANTOS, Raul D.Background and aims: Familial hypercholesterolemia (FH) is a genetic disorder associated with high risk of early major cardiovascular events (MACE) that can impact the health related quality of life (HRQoL), however, this association is unclear. This study evaluated HRQoL in index cases (IC) and first-degree relatives (FDR) of individuals at high risk of FH undergoing genetic cascade screening. Methods: Data collection was performed before awareness of molecular diagnosis results. Individuals were divided into four groups according to the molecular diagnosis: IC with (ICthorn) and without (IC-) identified mutations (n = 93 and n = 175, respectively), and affected (FDRthorn, n = 231) and non-affected (FDR-, n = 159) FDR of ICthorn. HRQoL measurements, mental (MCS) and physical component (PCS) scores were carried out with SF-12 questionnaire. Associations were tested by generalized linear models. Results: The mean age was 49 +/- 15 years, 42.2% were men, MACE had occurred in 30.7%. Overall, both PCS and MCS did not differ between FH and non-FH individuals, however, IC trended to have lower PCS independent of FH presence (p = 0.003). Lower PCS were associated with female sex (p = 0.018), lower education (p < 0.001), professional inactivity (p = 0.028), previous MACE occurrence (p < 0.001), hypertension (p = 0.016), depression (p < 0.001) and obesity (p < 0.001). Lower MCS were associated with female sex (p = 0.009), previous MACE occurrence (p = 0.034), depression (p < 0.001) and smoking (p = 0.009). Neither the presence of FH causing mutations nor pharmacological lipid lowering treatment was associated with HRQoL. Conclusions: HRQoL is not reduced in both IC and FDR FH individuals in comparison with their nonaffected counterparts. Previous MACE and co-morbidities are associated with reduced HRQoL.
- MTRR rs326119 polymorphism is associated with plasma concentrations of homocysteine and cobalamin, but not with congenital heart disease or coronary atherosclerosis in Brazilian patients(2017) HORITA, Melanie; BUENO, Carolina Tosin; HORIMOTO, Andrea R.; LEMOS, Pedro A.; MORANDINI-FILHO, Antonio A.; KRIEGER, Jose E.; SANTOS, Paulo C. J. L.; PEREIRA, Alexandre C.Background: Differences in the distribution of the MTRR rs326119 polymorphism (c.56+ 781 A>C) between patients with congenital heart disease (CHD) and controls have been described in Chinese individuals. The association is thought to be due to deregulation of homocysteine-cobalamin pathways. This has not been replicated in other populations. The primary objective of this study was to assess the influence of the MTRR rs326119 polymorphism on biochemical parameters of vitamin B12 metabolism, coronary lesions, and congenital heart disease in Brazilian subjects. Methods: We selected 722 patients with CHD, 1432 patients who underwent coronary angiography, and 156 blood donors. Genotyping for the MTRR polymorphism was evaluated by high-resolution melting analysis, and biochemical tests of vitamin B12 metabolism were measured. Results: Subjects carrying the AC or CC genotypes had higher homocysteine concentrations (9.7 +/- 0.4 mu mol/L and 10.1 +/- 0.6 mu mol/L) and lower cobalamin concentrations (260.5 +/- 13.3 pmol/L and 275.6 +/- 19.9 pmol/L) compared with the subjects carrying the AA genotype (8.7 +/- 0.5 mu mol/L and 304.8 +/- 14.7 pmol/L), respectively. A multiple linear regression model also identified a significant association between the number of C variant alleles with the concentrations of homocysteine and cobalamin. Nonetheless, the allelic and genotypic distributions for MTRR rs326119 were not associated with CHD or coronary atherosclerosis in the studied samples. Conclusion: Our findings indicate that the MTRR rs326119 variant might be a genetic marker associated with homocysteine and cobalamin concentrations, but not a strong risk factor for CHD or coronary atherosclerosis in the Brazilian population. (C) 2016 The Authors.
- Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery(2011) GOWDAK, Luis Henrique Wolff; SCHETTERT, Isolmar Tadeu; ROCHITTE, Carlos Eduardo; LISBOA, Luiz Augusto Ferreira; DALLAN, Luis Alberto Oliveira; CESAR, Luiz Antonio Machado; OLIVEIRA, Sergio Almeida de; KRIEGER, Jose EduardoIncomplete revascularization is associated with worse long-term outcomes. Autologous bone marrow cells (BMC) have recently been tested in patients with severe coronary artery disease. We tested the hypothesis that intramyocardial injection of autologous BMC increases myocardial perfusion in patients undergoing incomplete coronary artery bypass grafting (CABG). Twenty-one patients (19 men), 59 +/- 7 years old, with limiting angina and multivessel coronary artery disease (CAD), not amenable to complete CABG were enrolled. BMC were obtained prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing 2.1 +/- 1.3 x 10(8) BMC (CD34+ = 0.8 +/- 0.3%) were injected in the ischemic non-revascularized myocardium. Myocardial perfusion was assessed by magnetic resonance imaging (MRI) at baseline and 1 month after surgery. The increase in myocardial perfusion was compared between patients with < 50% (group A, n = 11) with that of patients with > 50% (group B, n = 10) of target vessels (stenosis a parts per thousand yenaEuro parts per thousand 70%) successfully bypassed. Injected myocardial segments included the inferior (n = 12), anterior (n = 7), and lateral (n = 2) walls. The number of treated vessels (2.3 +/- 0.8) was significantly smaller than the number of target vessels (4.2 +/- 1.0; P < 0.0001). One month after surgery, cardiac MRI showed a similar reduction (%) in the ischemic score of patients in group A (72.5 +/- 3.2), compared to patients in group B (78.1 +/- 3.2; P = .80). Intramyocardial injection of autologous BMC may help increase myocardial perfusion in patients undergoing incomplete CABG, even in those with fewer target vessels successfully treated. This strategy may be an adjunctive therapy for patients suffering from a more advanced (diffuse) CAD not amenable for complete direct revascularization.
- Screening of ABCG5 and ABCG8 Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program(2022) TADA, Mauricio Teruo; ROCHA, Viviane Zorzanelli; LIMA, Isabella Ramos; OLIVEIRA, Theo Gremen Mimary; CHACRA, Ana Paula; MINAME, Marcio Hiroshi; NUNES, Valeria Sutti; NAKANDAKARE, Edna Regina; CASTELO, Maria Helane Costa Gurgel; JANNES, Cinthia Elim; SANTOS, Raul D.; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaBackground: Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in ABCG5/ABCG8. The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease. The present study aims to characterize the prevalence and clinical features of sitosterolemia participating in a familial hypercholesterolemia genetic cascade screening program. Methods: From 443 familial hypercholesterolemia index cases, 260 were negative for familial hypercholesterolemia genes and were sequenced for the ABCG5/8 genes. Clinical and laboratory characteristics of affected individuals were determined. Results: Eight (3.1%) index cases were found to be homozygous or compound heterozygous variant for ABCG5/ABCG8 genes, confirming the genetic diagnosis of sitosterolemia. Screening their relatives led to the identification of 6 additional confirmed sitosterolemia cases (3 homozygous and 3 compound heterozygous variant) and 18 carriers (heterozygous). The mean age of identified sitosterolemia cases (n=14) was 37.2 +/- 19.8 years, 50% were females, and 78.6% (all adults) presented either clinical or subclinical atherosclerotic cardiovascular disease. As expected, affected individuals presented elevated plasma plant sterol levels (mean beta-Sitosterol and campesterol, respectively, 160.3 +/- 107.1 and 32.0 +/- 19.6 mu g/mL) and the highest plasma LDL (low-density lipoprotein)-cholesterol was 269.0 +/- 120.0 mg/dL (range: 122-521 mg/dL). LDL-cholesterol mean reduction with therapy among cases was 65%. Eighty-three percent (83%) of identified sitosterolemia patients presented hematologic abnormalities. Conclusions: Testing genes associated with sitosterolemia in the molecular routine workflow of a familial hypercholesterolemia cascade screening program allowed the precise diagnosis of sitosterolemia in a substantial number of patients with varying LDL-C levels and high incidence of early atherosclerotic cardiovascular disease and hematologic abnormalities.