PAMELA RODRIGUES DE SOUZA SILVA
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
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- 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.
- 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.
- Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy(2019) MINAME, Marcio H.; BITTENCOURT, Marcio Sommer; MORAES, Sergio R.; ALVES, Romulo I. M.; SILVA, Pamela R. S.; JANNES, Cinthia E.; PEREIRA, Alexandre C.; KRIEGER, Jose E.; NASIR, Khurram; SANTOS, Raul D.OBJECTIVES The aim of this study was to evaluate the role of coronary artery calcium (CAC) as a predictor of atherosclerotic cardiovascular disease (ASCVD) (fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (FH) subjects receiving standard lipid-lowering therapy. BACKGROUND FH is associated with premature ASCVD. However, the clinical course of ASCVD in subjects with FH is heterogeneous. CAC score, a marker of subclinical atherosclerosis burden, may optimize ASCVD risk stratification in FH. METHODS Subjects with FH underwent CAC measurement and were followed prospectively. The association of CAC with ASCVD was evaluated using multivariate analysis. RESULTS A total of 206 subjects (mean age 45 +/- 14 years, 36.4% men, baseline and on-treatment low-density lipoprotein cholesterol 269 +/- 70 mg/dl and 150 +/- 56 mg/dl, respectively) were followed for a median of 3.7 years (interquartile range: 2.7 to 6.8 years). CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost one-half of events were hard outcomes, and the others were elective myocardial revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1 to 100 (n = 62 [30%]) and >100 (n = 43 [21%]) were, respectively, 0, 26.4 (95% confidence interval: 12.9 to 51.8), and 44.1 (95% confidence interval, 26.0 to 104.1). In multivariate Cox regression analysis, log(CAC score 1) was independently associated with incident ASCVD events (hazard ratio: 3.33; 95% CI: 1.635 to 6.790; p = 0.001). CONCLUSIONS CAC was independently associated with ASCVD events in patients with FH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies. (C) 2019 by the American College of Cardiology Foundation.
- Evaluation of clinical and laboratory parameters used in the identification of index cases for genetic screening of familial hypercholesterolemia in Brazil(2017) SILVA, Pamela R. S.; JANNES, Cinthia E.; OLIVEIRA, Theo G. M.; MINAME, Marcio H.; ROCHA, Viviane Z.; CHACRA, Ana Paula; GURGEL, Maria Helane C.; MONTENEGRO, Renan M.; RODRIGUES SOBRINHO, Carlos Roberto M.; MOREIRA, Annie Seixas Bello; ASSAD, Marcelo H. V.; PINTO, Marina R. C.; TADA, Mauricio Teruo; SANTOS, Raul D.; PEREIRA, Alexandre C.; KRIEGER, Jose E.Background and aims: There is controversy on the accuracy of different diagnostic criteria for familial hypercholesterolemia (FH). The aim of this study is to assess the performance of different clinical criteria used to identify individuals for FH genetic cascade screening in Brazil. Methods: All index cases (IC) registered in the Hipercol Brasil program between 2011 and 2016 were analyzed. Inclusion criteria were age > 18 years and elevated LDL-cholesterol (LDL-C) levels, with a conclusive result in the genetic test, whether positive or negative. Initially, we tested the multivariable association between clinical and laboratory markers and the presence of an FH causing mutation. Then, we analyzed sensitivity, specificity, positive and negative predictive values for the LDL-C quartile distribution, LDL-C as a continuous variable, as well as the performance measures for the Dutch Lipid Clinic Network (DLCN) score to identify a mutation. Results: Overall, 753 ICs were included and an FH causing mutation was found in 34% (n = 257) of the subjects. After multivariable analysis, LDL-C as a continuous variable, tendon xanthomas and corneal arcus were independently associated with the presence of FH mutations. LDL-C values >= 230 mg/dL (5.9 mmol/L) had the best tradeoff between sensitivity and specificity to diagnose a mutation. The DLCN score presented a better performance than LDL-C to identify a mutation, area under the ROC curve were 0.744 (95% CI: 0.704-0.784) and 0.730 (95% CI: 0.687-0.774), respectively, p = 0.014. Conclusions: In our population, LDL >= 230 mg/dL is a feasible criterion to indicate ICs to genetic testing. (C) 2017 Published by Elsevier Ireland Ltd.