PAMELA RODRIGUES DE SOUZA SILVA
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Coronary Artery Calcium Score and Risk of Cardiovascular Events in Heterozygous Familial Hypercholesterolemia Patients Undergoing Standard Lipid Lowering Therapy(2018) MINAME, Marcio; BITTENCOURT, Marcio S.; MORAES, Sergio R.; I, Romulo Alves; SILVA, Pamela R.; JANNES, Cinthia E.; PEREIRA, Alexandre C.; NASIR, Khurram; SANTOS, Raul D.- CORONARY ARTERY CALCIFICATION IS SUPERIOR TO CLASSICAL RISK FACTORS AS PREDICTOR OF CARDIOVASCULAR DISEASE IN FAMILIAL HYPERCHOLESTEROLEMIA(2018) MINAME, Marcio; ALVES, Romulo; MORAES, Sergio; SILVA, Pamela; BITTENCOURT, Marcio; JANNES, Cinthia; PEREIRA, Alexandre; SANTOS, Raul
- Heterozygous familial hypercholesterolaemia in specialist centres in South Africa, Australia and Brazil: Importance of early detection and lifestyle advice(2018) PANG, Jing; MARAIS, A. David; BLOM, Dirk J.; BRICE, Brigitte C.; SILVA, Pamela R. S.; JANNES, Cinthia E.; PEREIRA, Alexandre C.; HOOPER, Amanda J.; RAY, Kausik K.; SANTOS, Raul D.; WATTS, Gerald F.Background and aims: Familial hypercholesterolaemia (FH) is the commonest monogenic disorder that accelerates atherosclerotic cardiovascular disease. We compared and contrasted the characteristics of patients from three specialist centres in the southern hemisphere. Methods: Adult index-cases with molecularly diagnosed heterozygous FH attending specialist lipid centres in Cape Town, Perth and Sao Paulo were studied. Myocardial infarction, revascularisation, hypertension, diabetes, smoking and lipid-lowering treatment were recorded at the time of diagnosis and compared across the three centres. Results: The spectrum of genetic variants causative of FH was significantly different in patients attending the centres in South Africa compared with Australia and Brazil. Hypertension and diabetes were more prevalent in Brazilian and Australian patients, than in South African patients, but the frequency of smoking was significantly greater in South Africa than the other two centres (p<0.01). Age, male sex and smoking were significant independent predictors of coronary artery disease (CAD) in all three countries (p<0.05). Conclusions: Patients with FH in three specialist centres in the southern hemisphere exhibit a high prevalence of non-cholesterol cardiovascular disease risk factors. Older age, male sex and smoking were more common among subjects with CAD. In all three countries, there should be vigorous programmes for the control of risk factors beyond good control of hypercholesterolaemia among patients with FH. Promotion of a healthy lifestyle, especially anti-smoking advice, is of paramount importance. (c) 2018 Published by Elsevier B.V.
- Achilles tendon xanthomas are associated with the presence and burden of subclinical coronary atherosclerosis in heterozygous familial hypercholesterolemia: A pilot study(2017) MANGILI, Leonardo C.; MINAME, Marcio H.; SILVA, Pamela R. S.; BITTENCOURT, Marcio S.; ROCHA, Viviane Z.; MANGILI, Otavio C.; SALGADO FILHO, Wilson; CHACRA, Ana P.; JANNES, Cinthia E.; PEREIRA, Alexandre C.; SANTOS, Raul D.Background and aims: Achilles tendon xanthomas (ATX) are a sign of long-term exposure to high blood cholesterol in familial hypercholesterolemia (FH) patients, which have been associated with cardiovascular disease. We evaluated the ATX association with the presence and extent of subclinical coronary atherosclerosis in heterozygous FH patients. Methods: 102 FH patients diagnosed by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279 mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease, underwent computed tomography angiography and coronary artery calcium (CAC) quantification. Subclinical coronary atherosclerosis was quantified by CAC, segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson regression was used to assess the association of ATX with subclinical atherosclerosis burden as continuous variables. Results: Patients with ATX (n = 21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as greater CAC scores, SIS and SSS (p < 0.05). After adjusting for age, sex, smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a) concentrations, there was an independent positive association of ATX presence with CAC scores (beta = 1.017, p < 0.001), SSS (beta = 0.809, p < 0.001) and SIS (beta = 0.640, p < 0.001). Conclusions: ATX are independently associated with the extension of subclinical coronary atherosclerosis quantified by tomographic scores in FH patients.
conferenceObject Coronary artery calcification is an independent predictor of cardiovascular events in familial hypercholesterolemia(2017) MINAME, M. H.; SILVA, P. R. S.; ALVES, R. L. M.; MORAES, S. R.; BITTENCOURT, M. S.; ROCHA, V. Z.; MARTE, A. P.; SALGADO, W.; JANNES, C. E.; PEREIRA, A. C.; SANTOS, R. D.- Dexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activation(2017) GUIMARAES, Fabiana de Salvi; MORAES, Wilson Max Almeida Monteiro de; BOZI, Luis Henrique Marchesi; SOUZA, Pamela R.; ANTONIO, Ednei Luiz; BOCALINI, Danilo Sales; TUCCI, Paulo Jose Ferreira; RIBEIRO, Daniel Araki; BRUM, Patricia Chakur; MEDEIROS, AlessandraDexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (similar to 400 g) were treated with dexamethasone (35 A mu g/g) in drinking water for 15 days. After dexamethasone treatment, we analyzed cardiac function, cardiomyocyte diameter, cardiac fibrosis, and the expression of proteins involved in calcium handling and calcineurin signaling pathway. Dexamethasone-treated rats showed several cardiovascular abnormalities, including elevated blood pressure, diastolic dysfunction, cardiac fibrosis, and cardiomyocyte apoptosis. Regarding the expression of proteins involved in calcium handling, dexamethasone increased phosphorylation of phospholamban at threonine 17, reduced protein levels of Na+/Ca2+ exchanger, and had no effect on protein expression of Serca2a. Protein levels of NFAT and GATA-4 were increased in both cytoplasmic and nuclear faction. In addition, dexamethasone increased nuclear protein levels of calcineurin. Altogether our findings suggest that dexamethasone causes pathologic cardiac remodeling and diastolic dysfunction, which is associated with impaired calcium handling and calcineurin signaling pathway activation.
- HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA IN SPECIALIST CENTRES IN SOUTH AFRICA, AUSTRALIA AND BRAZIL: IMPORTANCE OF EARLY DETECTION AND LIFESTYLE ADVICE(2018) PANG, Jing; MARAIS, A. D.; BLOM, Dirk J.; BRICE, Brigitte C.; SILVA, Pamela R.; JANNES, Cinthia E.; PEREIRA, Alexandre C.; HOOPER, Amanda J.; RAY, Kausik K.; SANTOS, Raul D.; WATTS, Gerald F.
- Predictors of cardiovascular events after one year of molecular screening for Familial hypercholesterolemia(2016) SILVA, Pamela R. S.; JANNES, Cinthia E.; MARSIGLIA, Julia D. C.; KRIEGER, Jose E.; SANTOS, Raul D.; PEREIRA, Alexandre C.Background and aims: This study reports the first year follow-up of individuals enrolled in Brazil's genetic cascade screening program for Familial Hypercholesterolemia (FH), Hipercol Brasil. Predictors for the occurrence of cardiovascular (CV) events in individuals screened for FH were studied. Methods: This is an open prospective cohort of individuals who were included in a cascade genetic screening program for FH. The first prospective follow-up was carried out one year after patients received their genetic test result. Individuals included in this study were index cases (probands) and relatives with identified (M+) or not genetic mutations (M-). Logistic regression analysis was performed to determine predictive variables for the occurrence of CV events censored at one-year of follow-up. Results: A total of 818 subjects were included, 47 first CV events were ascertained, with 14 (29.7%) being fatal. For index cases, the only factor independently associated with increased risk of CV events was the presence of corneal arcus (OR: 9.39; 95% CI: 2.46-35.82). There was an inverse association of CV events with higher HDL-cholesterol levels (OR: 0.95; 95% CI: 0.90-0.99). For M+ relatives, risk factors associated with increased CV events risk were diabetes mellitus (OR: 7.97; 95% CI: 2.07-30.66) and tobacco consumption (OR: 3.70; 95% CI: 1.09-12.50). Conclusions: A high one-year incidence of CV events was found in this cascade-screening cohort. Predictors of events differed between index cases and relatives and can be useful for the development of preventive efforts in this highly susceptible group of individuals.
conferenceObject Familial Hypercholesterolemia in Children and Safety of Early Lipid-Lowering Treatment(2017) BELLUNGHI, Maria Sol; MINAME, Marcio; JANNES, Cinthia E.; SILVA, Pamela R.; PEREIRA, Alexandre; CHACRA, Ana Paula; SALGADO, Wilson; SANTOS, Raul D.; ROCHA, Viviane Z.- Predictors of Family Enrollment in a Genetic Cascade Screening Program for Familial Hypercholesterolemia(2018) SILVA, Pamela Rodrigues de Souza; JANNES, Cinthia Elim; OLIVEIRA, Theo G. M.; GOMEZ, Luz Marina Gomez; KRIEGER, Jose E.; SANTOS, Raul D.; PEREIRA, Alexandre CostaBackground: Genetic cascade screening is the most cost-effective method for the identification of individuals with familial hypercholesterolemia (FH), but the best strategies for the enrollment of at-risk individuals in a FH screening program are not fully known. Objective: The aim of this study is to identify the best predictors of familial enrollment into genetic screening, using features derived from tested probands. Methods: One hundred and eighty-three index-cases (ICs) with a positive genetic result that had relatives screened from 01/2011 to 07/2015 were included. The response variable was the number of relatives for each enrolled IC. All variables in the study were based on ICs' derived clinical and socioeconomical features. The effect size of predictor variables were obtained through a general linear model using a negative binomial regression link function. Significance was considered with a p < 0.05. Results: Mean IC age when enrolling into the program was 50 years old; 78.1% of individuals reported knowledge of relatives with dyslipidemia. Mean baseline LDL-cholesterol level was 316 +/- 90 mg/dL. Referral origin through the cascade program website vs. tertiary care, IC LDL-cholesterol and familial history of high LDL-cholesterol levels were independent predictors associated with a higher number of enrolled relatives. Conclusions: Our data suggest that FH cascade screening programs can predict family enrollment based on IC features. This information may be useful for devising better and more effective screening approaches for at-risk individuals.