Browsing by Author "Francisco, V."
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- Cardiovascular risk profile of high school students: A cross-sectional studyPublication . Rocha, T.; Rocha, E.; Alves, A.C.; Medeiros, A.M.; Francisco, V.; Silva, S.; Mendes Gaspar, I.; Rato, Q.; Bourbon, M.INTRODUCTION: Disease prevention should begin in childhood and lifestyles are important risk determinants of cardiovascular disease. Awareness and monitoring of risk is essential in preventive strategies. AIM: To characterize cardiovascular risk and the relationships between certain variables in adolescents. METHODS: In a cross-sectional study, 854 adolescent schoolchildren were surveyed, mean age 16.3±0.9 years. Data collection included questionnaires, physical examination, charts for 10-year relative risk of mortality, and biochemical assays. In the statistical analysis continuous variables were studied by the Student's t test and categorical variables by the chi-square test and Fisher's exact test, and each risk factor was entered as a dependent variable in logistic regression analysis. RESULTS: Physical activity was insufficient in 81% of students. The daily consumption of soup, salad or vegetables, and fruit was, respectively, 37%, 39% and 21%. A minority (6%) took ≤3 and 77% took ≥5 meals a day. The prevalence of each risk factor was as follows: overweight 16%; smoking 13%; hypertension 11%; impaired glucose metabolism 9%; hypertriglyceridemia 9%; and hypercholesterolemia 5%. Out-of-school physical activity, hypertension and overweight were more prevalent in males (p<0.001). Females had higher levels of cholesterol (p<0.005) and triglycerides (p<0.001). A quarter of the adolescents had a relative risk score for 10-year cardiovascular mortality of ≥2. Overweight showed a positive association with blood pressure, changes in glucose metabolism and triglycerides, and a negative association with number of daily meals. CONCLUSIONS: The results demonstrate the need for action in providing and encouraging healthy choices for adolescents, with an emphasis on behavioral and lifestyle changes aimed at individuals, families and communities
- Estudo Português de Hipercolesterolemia FamiliarPublication . Medeiros, A.M.; Alves, A.C.; Francisco, V.; Bourbon, M.A Hipercolesterolemia Familiar (FH) é uma doença autossómica dominante que se caracteriza, a nível clínico, por níveis elevados de colesterol LDL, levando ao aparecimento prematuro de doenças cardiovasculares (DCV). A nível genético esta doença caracteriza-se, principalmente, por mutações em três genes: LDLR, APOB e PCSK9. Estima-se que em Portugal existam cerca de 20 000 doentes com FH. A identificação clínica de FH é possível mas apenas o estudo molecular confirma a presença da doença. O Estudo Português de Hipercolesterolemia Familiar (EPFH) tem como objectivo principal identificar a causa genética da dislipidémia em doentes com diagnóstico clínico de FH. O EPHF recebeu desde 1999, para realização do estudo molecular, 486 casos-index com diagnóstico clínico de FH e 858 familiares. O estudo molecular é realizado em 3 fases. Fase I: Identificação de mutações nos genes APOB e LDLR. Fase II: Pesquisa de grandes rearranjos no gene LDLR por MLPA. Fase III: Pesquisa de mutações no gene PCSK9. A pesquisa de mutações nos genes APOB e PCSK9 é realizada por amplificação dos fragmentos a estudar e sequenciação directa. No gene LDLR os 18 exões são amplificados dos 18 exôes por PCR e analisados por DHPLC e sequenciação. Até à data foram identificados um total de 504 doentes com um defeito genético num dos três genes estudados: 3 doentes com mutação no gene PCSK9, 12 doentes com mutação no gene APOB e 438 doentes com mutação no gene LDLR (7 dos quais em homozigotia ou heterozigotia composta). No gene LDLR foram encontradas 89 mutações diferentes, que incluem 43 mutações missense,17 delecções/inserções, 6 nonsense, 12 mutações de splicing, 4 grandes delecções e 2 no promotor e 1no codão stop. As mutações mais comuns na população portuguesa são: p.A431T (11%), p.D224N (6,9%) e p.R406W (6,2%). Foram efectuados funcionais em algumas mutações de splicing e comprovou-se a sua patogeneicidade em 6 alterações (c.-135C>G; c.-190+4insTG; c.313+6T>C; c.818-2A>G; c.2389G>T (V776L); c.2547+1G>A). Foram também efectuados estudos funcionais para 5 alterações missense não descritas anteriormente (p.V429L, p.W490R, p.S648P, p.P685S e p.V859M), verificou-se que apenas a alteração p.V859M não é patogenica. No gene APOB foi identificada a mutação mais comum (p.Arg3527Gln) e também a mutação p.Tyr3560Cys. No gene PCSK9 foi encontrada uma única alteração, p.Asp374His. A FH esta sub-diagnosticada no nosso País, esforços têm de ser conduzidos para identificar estes doentes, ainda em idade jovem, de modo a que seja evitado o aparecimento da DCV prematura, e no caso mais extremo a morte prematura como observado em algumas famílias. O diagnóstico e aconselhamento genético da FH é importante para a correcta percepção e prevenção do risco familiar de DCV. O estudo molecular fundamenta a instituição de terapêutica farmacológica adequada e a adopção de um estilo de vida saudável reduzindo substancialmente o risco cardiovascular. Nas crianças e adolescentes o diagnóstico genético é ainda mais importante, uma vez que se sabe que o risco cardiovascular é elevado, mas evitável, se medidas preventivas forem colocadas em prática. O futuro passa pela prevenção em vez da resolução tardia das complicações cardiovasculares inerentes a esta patologia.
- Lifestyle Habits and Cardiovascular Risk Factors in a Young PopulationPublication . Medeiros, A.M.; Rocha, T.M.; Francisco, V.; Alves, A.C.; Santos, T.; Louro, M.H.; Gonçalves, C.; Bourbon, M.Although CVD is mostly present in adult life, atherosclerosis starts in childhood. Health promotion and cardiovascular prevention strategies can generate health gains and, if implemented in childhood, those gains will be superior. In pathologies with multifactorial etiology like CVD, the preventive approach should be addressed to risk factors, specially the modifiable related to unhealthy lifestyle habits. The aims of this work are: to characterize the lifestyle habits and determine the cardiovascular risk factors of a young population, and to co-relate these factors.
- Molecular diagnosis of familial hypercholesterolemia: an important tool for cardiovascular risk stratificationPublication . Alves, A.C.; Medeiros, A.M.; Francisco, V.; Gaspar, I.M.; Rato, Q.; Bourbon, M.Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. Molecular identification of these patients can reduce the burden of mortality from cardiovascular disorders simply by the correct identification of the disease early in life, followed by counseling and appropriate lifestyle modifications, and therapeutic measures when required. Recent studies show that, in Portugal, this disease is severely under-diagnosed. After more than 10 years of research through the Portuguese FH Study, it is now possible to translate the original research results into clinical application. AIMS: The main aims of the present work were to determine whether clinical characterization is sufficient to identify these individuals at high risk of developing CHD and to evaluate the clinical applicability of molecular diagnosis for FH. METHODS: All patients described in this study were recruited for the Portuguese FH Study. The diagnostic criteria used to select the index patients were adapted from the Simon Broome Heart Research Trust. To analyze the usefulness of the molecular diagnosis, graphs of total and LDL cholesterol values by age were constructed for 622 possible FH patients. The lipid profile of patients genetically identified as having FH, before and under medication, were analyzed to assess whether these patients were receiving appropriate treatment. The data are shown separately for children and adults and for female and male propositi (index cases and hypercholesterolemic relatives), both with and without a detectable mutation in the LDLR gene. RESULTS: The Portuguese FH Study has already genetically identified 404 individuals (171 index patients and 233 relatives) among more than one thousand individuals sent for study. A total of 78 different mutations in the LDLR gene were found in 171 index patients, 2 different mutations were found in the apoB gene of 4 patients and 2 patients had a unique PCSK9 mutation. Statistical analysis revealed that there are significant differences between total cholesterol (p < 0.001) and apoB (p = 0.026) values in the group of children (male and female) with and without a mutation in LDLR. For female children LDL values were also significantly different (p < 0.001) between subgroups but for male children this difference did not reach statistical significance. In adult women there is a statistically significant difference for total cholesterol (p = 0.049), LDL cholesterol (p = 0.031) and apoB (p = 0.003) values in the subgroups with and without a LDLR mutation. In adult males there is a statistical difference for total cholesterol (p = 0.002). LDL cholesterol (p = 0.003) and apoB (p = 0.0023) in subgroups with and without an LDLR mutation. Nevertheless there was considerable dispersion of values and individually it is not possible to distinguish between patients with and without a mutation in the LDLR gene, based only on lipid profile. CONCLUSIONS: By analysis of the clinical data of 696 possible FH patients, the present report shows evidence that clinical characterization is not sufficient to distinguish between patients with genetic or environmental dyslipidemia, and so molecular diagnosis is useful in clinical practice, allowing correct identification of FH patients and their relatives, and the early implementation of therapeutic measures to reduce the elevated cardiovascular risk of these patients. In general, molecular diagnosis of FH is feasible and could be obtained in 1-2 months if the technology is available. In Portugal the test will be offered to the population by our Institute at a cost of about 500 euros, like many other genetic tests or exams such as nuclear magnetic resonance.
- Perfil de risco cardiovascular de estudantes do ensino secundárioPublication . Rocha, T.; Alves, A.; Medeiros, A.; Francisco, V.; Silva, S.; Guiomar, S.; Paixão, E.; Gaspar, I.; Rato, Q.; Bourbon, M.
- Portuguese Familial Hypercholesterolemia StudyPublication . Medeiros, A.M.; Alves, A.C.; Francisco, V.; Bourbon, M.Familial hypercholesterolemia (FH) is an autossomal dominant disorder associated with high levels of plasma cholesterol and premature coronary heart disease (pCHD), with a frequency of 1/500. The major aim of the Portuguese FH Study is to identify the genetic cause of disease in patients with clinical diagnosis of FH so patients can receive counselling and treatment in time to prevent the development of pCHD. The clinical criteria used is from the Simon Broome Register (UK) and the genetic diagnosis was performed by the analysis of 18 fragments of the LDLR, 2 of the APOB and 5 of the PCSK9. These fragments are amplified by PCR and analysed by dHPLC and sequenced and MLPA to identify potential mutations. The Portuguese FH Study identified a genetic defect in 420 patients: 60 children, 122 adults (index patients) and 56 children, 182 adults (relatives), which represent only 2,1% of the FH cases estimated to exist in Portugal. The majority of index patients had a genetic defect in LDLR and 25% of the adults had pCHD. From the 238 relatives with FH identified by cascade screening, 13% of the adults had pCHD and 76 individuals in these families died from pCHD. The genetic diagnosis of FH confirms the clinical diagnosis based on plasma cholesterol levels and provides unequivocal diagnosis of patients and early identification of relatives. The counselling of these patients should result in appropriate treatment and adoption of a healthier lifestyle, in order to reduce their risk of CHD and decrease avoidable deaths
- Update of the Portuguese Familial Hypercholesterolaemia StudyPublication . Medeiros, A.M.; Alves, A.C.; Francisco, V.; Bourbon, M.; Investigators of the Portuguese FH StudyThe main aim of the Portuguese Familial Hypercholesterolaemia Study is to identify the genetic cause of hypercholesterolaemia in individuals with a clinical diagnosis of Familial Hypercholesterolaemia (FH). A total of 1340 blood samples were collected from 482 index patients and 858 relatives with the collaboration of clinicians from several hospitals all over the country. The genetic diagnosis of FH in this study is based on the analyses of three genes: LDLR, APOB and PCSK9. In the last 10 years, the Portuguese FH Study identified a genetic defect in a total of 171 index patients, corresponding to an overall of 48% of the total received cases with clinical diagnosis of FH. Although the Simon Broome FH register criteria have been adapted to our study, 59 patients that did not fulfil all criteria were included in the study and a mutation causing disease was identified in 8 of these patients. In the LDLR gene were found 80 different mutations in 165 unrelated index patients: 159 heterozygous, 3 compounds heterozygous and 3 true homozygous. The APOB p.Arg3527Gln and the PCSK9 p.Asp374His mutation were not found in any of our patients since our last report, but a novel mutation in the APOB gene, predicted to cause a single amino acid substitution p.Tyr3560Cys, was found in one patient. The cascade screening in relatives of these 171 index patients allowed the identification and genetic characterization of a total of 404 FH patients in Portugal.