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Gender and age are well-established determinants of health and sleep health that influence overall health, which also often varies by gender and age. Sleep architecture is an important component of sleep health. The goal of this analysis was to examine whether associations between age and sleep stages differ by gender in the absence of moderate-severe obstructive sleep apnea (OSA) in a rural setting in Brazil. This study conducted polysomnography recordings in the Baependi Heart Study, a cohort of Brazilian adults. Our sample included 584 women and 309 men whose apnea-hypopnea index was ≤15 events/h. We used splines to distinguish non-linear associations between age, total sleep time, wake after sleep onset (WASO), N2, N3, and rapid-eye-movement sleep. The mean (standard deviation; range) age was 47 (14; 18-89) years. All sleep outcomes were associated with age. Compared to men, women had more N3 sleep and less WASO after adjusting for age. Model-based comparisons between genders at specific ages showed statistically higher mean WASO for men at ages 60 (+13.6 min) and 70 years (+19.5 min) and less N3 for men at ages 50 (-13.2 min), 60 (-19.0 min), and 70 years (-19.5 min) but no differences at 20, 30, 40 or 80 years. The other sleep measures did not differ by gender at any age. Thus, even in the absence of moderate-severe OSA, sleep architecture was associated with age across adulthood, and there were gender differences in WASO and N3 at older ages in this rural community.
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BACKGROUND: High blood pressure (BP) increases carotid intima-media thickness (CIMT). On the other hand, it is not clear whether the vascular abnormalities reflected in high CIMT may predict incident hypertension. The present study aims to investigate the association between CIMT and incident hypertension after 4 years of follow-up in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multiethnic sample of middle-aged adults from six Brazilian cities. METHODS: We analyzed data from 6682 ELSA-Brasil participants (aged 35-74) without hypertension and with complete CIMT data at baseline. After 4 years of follow-up, we describe hypertension incidence, stratifying the sample according to age, sex, and race-specific CIMT quartiles. We also built crude and adjusted Poisson regression models to analyze the association between mean and maximal CIMT values and incident hypertension. RESULTS: We found incident hypertension in 987 (14.8%) participants. According to mean CIMT quartile groups, hypertension incidence varied from 10.2% (first quartile group) to 22.4% (fourth quartile group; P for trend <0.001). In fully adjusted models, 0.1âmm increments in mean CIMT values were associated with a 16% [relative risk (RR):1.16; 95% confidence interval (95% CI) 1.10-1.21; P â<â0.001] higher risk of incident hypertension, respectively. Results were similar when maximal CIMT values were considered instead of mean CIMT values. CONCLUSION: CIMT values at baseline strongly predicted incident hypertension after 4 years of follow-up in this large multiethnic cohort. This highlights the relationship between CIMT and BP and may provide important insights into the significance of this ultrasound measurement.
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Grosor Intima-Media Carotídeo , Hipertensión , Persona de Mediana Edad , Adulto , Humanos , Estudios Longitudinales , Brasil/epidemiología , Factores de Riesgo , Hipertensión/epidemiologíaRESUMEN
Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.
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Chagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) ≥ 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.
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Cardiomiopatía Chagásica , Enfermedad de Chagas , Metilación , Enfermedades Parasitarias , Terapéutica , BiomarcadoresRESUMEN
Resumo Fundamento A associação entre o status de saúde cardiovascular ideal ( ideal cardiovascular health ( ICVH) e diagnóstico de fibrilação ou flutter atrial (FFA) foi menos estudado em comparação a outras doenças cardiovasculares. Objetivos Analisar a associação entre o diagnóstico de FFA e métricas e escores de ICVH no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Métodos Este estudo analisou dados de 13141 participantes com dados completos. Os traçados eletrocardiográficos foram codificados de acordo com o Sistema de Minnesota, em um centro de leitura centralizado. As métricas do ICVH (dieta, atividade física, índice de massa corporal, tabagismo, glicemia de jeju, e colesterol total) e escores do ICVH foram calculados conforme proposto pela American Heart Association . Modelos de regressão logística bruta e ajustada foram construídos para analisar associações de métricas e escores do ICVH com diagnóstico de FFA. O nível de significância foi estabelecido em 0,05. Resultados A idade mediana da amostra foi de 55 anos, e 54,4% eram mulheres. Nos modelos ajustados, os escores de ICVH não apresentaram associação significativa com diagnóstico de FFA prevalente [odds ratio (OR):0,96; intervalo de confiança de 95% (IC95%):0,80-1,16; p=0,70). Perfis de pressão arterial ideal (OR:0,33; IC95%:0,1-0,74; p=0,007) e colesterol total ideal (OR:1,88; IC95%:1,19-2,98; p=0,007) foram significativamente associados com o diagnóstico de FFA. Conclusões Não foram identificadas associações significativas entre escores de ICVH global e diagnóstico de FFA após ajuste multivariado em nossas análises, devido, ao menos em parte, às associações antagônicas da FFA com métricas de pressão arterial e de colesterol total do ICVH. Nossos resultados sugerem que estimar a prevenção da FFA por meio de escore de ICVH global pode não ser adequado, e as métricas do ICVH devem ser consideradas separadamente.
Abstract Background The association between ideal cardiovascular health (ICVH) status and atrial fibrillation or flutter (AFF) diagnosis has been less studied compared to other cardiovascular diseases. Objective To analyze the association between AFF diagnosis and ICVH metrics and scores in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods This study analyzed data from 13,141 participants with complete data. Electrocardiographic tracings were coded according to the Minnesota Coding System, in a centralized reading center. ICVH metrics (diet, physical activity, body mass index, smoking, blood pressure, fasting plasma glucose, and total cholesterol) and scores were calculated as proposed by the American Heart Association. Crude and adjusted binary logistic regression models were built to analyze the association of ICVH metrics and scores with AFF diagnosis. Significance level was set at 0.05. Results The sample had a median age of 55 years and 54.4% were women. In adjusted models, ICVH scores were not significantly associated with prevalent AFF diagnosis (odds ratio [OR]:0.96; 95% confidence interval [95% CI]:0.80-1.16; p=0.70). Ideal blood pressure (OR:0.33; 95% CI:0.15-0.74; p=0.007) and total cholesterol (OR:1.88; 95% CI:1.19-2.98; p=0.007) profiles were significantly associated with AFF diagnosis. Conclusions No significant associations were identified between global ICVH scores and AFF diagnosis after multivariable adjustment in our analyses, at least partially due to the antagonistic associations of AFF with blood pressure and total cholesterol ICVH metrics. Our results suggest that estimating the prevention of AFF burden using global ICVH scores may not be adequate, and ICVH metrics should be considered in separate.
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Abstract Background: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder, characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular disease. Objective: To evaluate clinical and anthropometric characteristics of patients with the familiar hypercholesterolemia (FH) phenotype, with or without genetic confirmation of FH. Methods: Forty-five patients with LDL-C > 190 mg/dl were genotyped for six FH-related genes: LDLR, APOB, PCSK9, LDLRAP1, LIPA and APOE. Patients who tested positive for any of these mutations were considered to have genetically confirmed FH. The FH phenotype was classified according to the Dutch Lipid Clinic Network criteria. Results: Comparing patients with genetically confirmed FH to those without it, the former had a higher clinical score for FH, more often had xanthelasma and had higher LDL-C and apo B levels. There were significant correlations between LDL-C and the clinical point score for FH (R = 0.382, p = 0.037) and between LDL-C and body fat (R = 0.461, p = 0.01). However, patients with mutations did not have any correlation between LDL-C and other variables, while for those without a mutation, there was a correlation between LDL-C and the clinical point score. Conclusions: LDL-C correlated with the clinical point score and with body fat, both in the overall patient population and in patients without the genetic confirmation of FH. In those with genetically confirmed FH, there were no correlations between LDL-C and other clinical or biochemical variables in patients.
Resumo Fundamentos: A hipercolesterolemia familiar (HF) é uma doença autossômica dominante, caracterizada por altos níveis plasmáticos do colesterol da lipoproteína de baixa densidade (LDL-C) e pelo alto risco de desenvolvimento prematuro de doenças cardiovasculares. Objetivo: Avaliar características clínicas e antropométricas de pacientes com fenótipo para hipercolesterolemia familiar (HF), com ou sem diagnóstico genético de HF. Métodos: Quarenta e cinco pacientes com LDL-C > 190 mg/dL foram genotipados para seis genes relacionados com a HF: LDLR, APOB, PCSK9, LDLRAP1, LIPA e APOE. Pacientes que apresentaram resultado positivo para qualquer uma das mutações foram diagnosticados com HF por confirmação genética. O fenótipo para HF foi classificado pelo critério da Dutch Lipid Clinic Network. Resultados: Comparando os pacientes com a HF geneticamente confirmada com aqueles sem a confirmação, os primeiros apresentaram maior pontuação do escore para HF, uma maior frequência de xantelasma e maiores níveis de LDL-C e apo B. Houve correlações significativas entre o LDL-C e a pontuação do escore para HF (R = 0,382, p = 0,037) e entre LDL-C e gordura corporal (R = 0,461, p = 0,01). Os pacientes com mutações, no entanto, não apresentaram qualquer correlação entre o LDL-C e outras variáveis, enquanto aqueles sem mutação apresentaram correlação entre o LDL-C e a pontuação do escore. Conclusão: O LDL-C correlacionou-se com a pontuação do escore e com a gordura corporal, tanto na população total de pacientes quanto nos pacientes sem a confirmação genética de HF. Naqueles com HF geneticamente confirmada, não houve correlação entre o LDL-C e outras variáveis clínicas ou bioquímicas dos pacientes.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Hipercolesterolemia/genética , Hiperlipoproteinemia Tipo II/genética , LDL-Colesterol/genética , Fenotipo , Pesos y Medidas Corporales , Estudios TransversalesRESUMEN
Abstract: There has been little cross-national comparison of perceived discrimination, and few studies have considered how intersectional identities shape perception of discriminatory treatment in different societies. Using data from the ELSA-Brasil, a study of Brazilian civil servants, and the Americans’ Changing Lives Study, a nationally-representative sample of U.S. adults, we compare reports of lifetime discrimination among race-by-gender groups in each society. We also consider whether educational attainment explains any group differences, or if differences across groups vary by level of education. Results reveal higher lifetime discrimination experiences among Black respondents in both countries, especially Black men, than among Whites, and lower reports among White women than White men. Brown men and women also reported higher levels than White men in Brazil. For all race-by-gender groups in both countries, except Brazilian White men, reports of discrimination were higher among the more educated, though adjusting for educational differences across groups did not explain group differences. In Brazil, we found the greatest racial disparities among the college educated, while U.S. Black men were more likely to report discrimination than White men at all levels of education. Results reveal broad similarities across countries, despite important differences in their histories, and an intersectional approach contributed to identification of these similarities and some differences in discrimination experiences. These findings have implications for social and public health surveillance and intervention to address the harmful consequences of discrimination.
Resumo: Há poucos estudos comparativos entre países sobre a experiência com a discriminação percebida, e poucos examinaram a maneira pela qual as identidades interseccionais configuram a percepção do tratamento discriminatório nas diferentes sociedades. Com base em dados do ELSA-Brasil (um estudo de funcionários públicos brasileiros) e do Americans’ Changing Lives Study (em uma amostra nacional representativa de adultos americanos), os autores comparam os relatos de grupos diferentes em relação à discriminação sofrida ao longo da vida, de acordo com raça e gênero, em cada sociedade. O estudo também investiga se o grau de escolaridade explica as diferenças entre grupos, ou se as diferenças dentro do mesmo grupo variam de acordo com a escolaridade. Os resultados mostram uma percepção maior de discriminação entre indivíduos negros em ambos os países, principalmente homens negros, comparado com brancos, além de menos relatos de discriminação sofrida por mulheres brancas comparado com homens brancos. No Brasil, mulheres e homens pardos relataram maiores níveis de discriminação em comparação com homens brancos. Com exceção de homens brancos, para todos os grupos analisados por raça e gênero, os relatos de discriminação foram mais frequentes entre os mais escolarizados, embora o ajuste por diferenças de escolaridade dentro dos grupos não explicasse as diferenças entre grupos. No Brasil, encontramos as maiores disparidades raciais entre indivíduos com nível superior, enquanto nos Estados Unidos, os homens negros relatavam mais discriminação do que os homens brancos, independentemente de grau de escolaridade. Os resultados revelam semelhanças gerais entre os dois países, apesar de importantes diferenças históricas. A abordagem interseccional contribuiu para a identificação dessas semelhanças e de algumas diferenças nas experiências com a discriminação. Os achados do estudo têm implicações importantes para a vigilância social e sanitária, assim como, para intervenções voltadas ao enfrentamento das consequências danosas da discriminação.
Resumen: Existen pocos estudios comparativos entre países sobre la experiencia con la discriminación percibida, y pocos examinaron la manera mediante la cual las identidades interseccionales configuran la percepción del tratamiento discriminatorio en las diferentes sociedades. En base a los datos del ELSA-Brasil (un estudio de funcionarios públicos brasileños) y del Americans’ Changing Lives Study (en una muestra nacional representativa de adultos americanos), los autores comparan los relatos de grupos diferentes, en relación a la discriminación sufrida a lo largo de la vida, de acuerdo con raza y género, en cada sociedad. El estudio también investiga si el grado de escolaridad explica las diferencias entre grupos, o si las diferencias dentro del mismo grupo varían de acuerdo con la escolaridad. Los resultados muestran una percepción mayor de discriminación entre individuos negros en ambos países, principalmente hombres negros, comparado con los blancos, además de menos relatos de discriminación sufrida por mujeres blancas, comparado con hombres blancos. En Brasil, mujeres y hombres mestizos relataron mayores niveles de discriminación, en comparación con los hombres blancos. Con excepción de hombres blancos, para todos los grupos analizados por raza y género, los relatos de discriminación fueron más frecuentes entre los más escolarizados, aunque el ajuste por diferencias de escolaridad dentro de los grupos no explicase las diferencias entre grupos. En Brasil, encontramos las mayores disparidades raciales entre individuos con nivel superior, mientras en los Estados Unidos, los hombres negros relataban más discriminación que los hombres blancos, independientemente del grado de escolaridad. Los resultados revelan semejanzas generales entre los dos países, a pesar de importantes diferencias históricas. El abordaje interseccional contribuyó a la identificación de esas semejanzas y de algunas diferencias en las experiencias con la discriminación. Los hallazgos del estudio tienen implicaciones importantes para la vigilancia social y sanitaria, así como, para intervenciones dirigidas a hacer frente a las consecuencias perniciosas de la discriminación.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Prejuicio/estadística & datos numéricos , Población Negra/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Factores Socioeconómicos , Estados Unidos , Negro o Afroamericano , Brasil , Factores Sexuales , Grupos Raciales , AutoinformeRESUMEN
ABSTRACT Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze the presence of a founder effect. We obtained DNA samples from 1,205 local inhabitants, 48 relatives of the homozygous patients and four individuals of another affected family. Genotyping for STAT5B c.424_427del mutation and for two polymorphic markers around it was done through fragment analysis technique. We also determined Y-chromosome and mtDNA haplotypes and genomic ancestry in heterozygous carriers. We identified seven families with STAT5B c.424_427del mutation, with 33 heterozygous individuals. The minor allelic frequency of this mutation was 0.29% in this population (confidence interval 95% 0.08-0.5%), which is significantly higher than the frequency of other pathogenic STAT5B allele variants observed in public databases (p < 0.001). All heterozygous carriers had the same haplotype present in the homozygous patients, found in only 9.4% of non-carriers (p < 0.001), supporting the existence of a founder effect. The Y-chromosome haplotype, mtDNA and genomic ancestry analysis indicated a European origin of this mutation. Our results provide compelling evidence for a founder effect of STAT5B c.424_427del mutation.
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AIM: functional analysis of pcsk9 3'utr variants and mrna-mirna interactions were explored in patients with familial hypercholesterolemia (fh). MATERIALS & METHODS: PCSK9 3'UTR variants were identified by exon-targeted gene sequencing. Functional effects of 3'UTR variants and mRNA-miRNA interactions were analyzed using in silico and in vitro studies in HEK293FT and HepG2 cells. RESULTS: Twelve PCSK9 3'UTR variants were detected in 88 FH patients. c.*75C >T and c.*345C >T disrupted interactions with miR-6875, miR-4721 and miR-564. Transient transfection of the c.*345C >T decreased luciferase activity in HEK293FT cells. miR-4721 and miR-564 mimics reduced PCSK9 expression in HepG2 cells. CONCLUSION: PCSK9 c.*345C >T has a possible role as loss-of-function variant. miR-4721 and miR-564 downregulate PCSK9 and may be useful to improve lipid profile in FH patients.
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MicroARNs , Epigenómica , Hiperlipoproteinemia Tipo II , Proproteína Convertasa 9RESUMEN
OBJECTIVES: To describe the ERICO study (Strategy of Registry of Acute Coronary Syndrome), a prospective cohort to investigate the epidemiology of acute coronary syndrome. METHODS: The ERICO study, which is being performed at a secondary general hospital in São Paulo, Brazil, is enrolling consecutive acute coronary syndrome patients who are 35 years old or older. The sociodemographic information, medical assessments, treatment data and blood samples are collected at admission. After 30 days, the medical history is updated, and additional blood and urinary samples are collected. In addition, a retinography, carotid intima-media thickness, heart rate variability and pulse-wave velocity are performed. Questionnaires about food frequency, physical activity, sleep apnea and depression are also applied. At six months and annually after an acute event, information is collected by telephone. RESULTS: From February 2009 to September 2011, 738 patients with a diagnosis of an acute coronary syndrome were enrolled. Of these, 208 (28.2%) had ST-elevation myocardial infarction (STEMI), 288 (39.0%) had non-ST-elevation myocardial infarction (NSTEMI) and 242 (32.8%) had unstable angina (UA). The mean age was 62.7 years, 58.5% were men and 77.4% had 8 years or less of education. The most common cardiovascular risk factors were hypertension (76%) and sedentarism (73.4%). Only 29.2% had a prior history of coronary heart disease. Compared with the ST-elevation myocardial infarction subgroup, the unstable angina and non-ST-elevation myocardial infarction patients had higher frequencies of hypertension, diabetes, prior coronary heart disease (p<0.001) and dyslipidemia (p = 0.03). Smoking was more frequent in the ST-elevation myocardial infarction patients (p = 0.006). CONCLUSIONS: Compared with other hospital registries, our findings revealed a higher burden of CV risk factors and less frequent prior CHD history.
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome Coronario Agudo/epidemiología , Enfermedad Coronaria/epidemiología , Sistema de Registros/normas , Brasil/epidemiología , Métodos Epidemiológicos , Reproducibilidad de los Resultados , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVES: Noonan and Noonan-related syndromes are common autosomal dominant disorders with neuro-cardio-facial-cutaneous and developmental involvement. The objective of this article is to describe the most relevant tegumentary findings in a cohort of 41 patients with Noonan or Noonan-related syndromes and to detail certain aspects of the molecular mechanisms underlying ectodermal involvement. METHODS: A standard questionnaire was administered. A focused physical examination and a systematic review of clinical records was performed on all patients to verify the presence of tegumentary alterations. The molecular analysis of this cohort included sequencing of the following genes in all patients: PTPN1, SOS1, RAF1, KRAS, SHOC2 and BRAF. RESULTS: The most frequent tegumentary alterations were xeroderma (46%), photosensitivity (29%), excessive hair loss (24%), recurrent oral ulcers (22%), curly hair (20%), nevi (17%), markedly increased palmar and plantar creases (12%), follicular hyperkeratosis (12%), palmoplantar hyperkeratosis (10%), café-au-lait spots (10%) and sparse eyebrows (7%). Patients with mutations in PTPN11 had lower frequencies of palmar and plantar creases and palmar/plantar hyperkeratosis compared with the other patients. CONCLUSIONS: We observed that patients with mutations in genes directly involved in cell proliferation kinase cascades (SOS1, BRAF, KRAS and RAF1) had a higher frequency of hyperkeratotic lesions compared with patients with mutations in genes that have a more complex interaction with and modulation of cell proliferation kinase cascades (PTPN11). .
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Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Síndrome de Noonan/patología , Enfermedades de la Piel/patología , Piel/patología , Quinasas MAP Reguladas por Señal Extracelular/genética , Mutación , Síndrome de Noonan/genética , Estudios Prospectivos , /genética , Factores Sexuales , Encuestas y Cuestionarios , Enfermedades de la Piel/genéticaRESUMEN
O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) é uma coorte prospectiva multicêntrica de funcionários públicos delineada para avaliar os determinantes das doenças crônicas, principalmente a doença cardiovascular e o diabetes tipo 2. Neste artigo são descritos os principais pontos do delineamento e implementação do projeto do biobanco do ELSA-Brasil. São detalhados aspectos econômicos, políticos, logísticos e tecnológicos do estudo. O artigo também discute o protocolo final de estocagem de material biológico e as instalações implementadas para atingir esse objetivo. O processo de delineamento e implementação do biobanco do ELSA-Brasil durou três anos. Tanto os biobancos centrais quanto os locais foram constituídos de acordo com as melhores práticas de estocagem de material biológico, usando soluções tecnológicas diferentes para as diferentes necessidades previstas no estudo.
The Brazilian Longitudinal Study for Adult Health (ELSA-Brasil) is a multicenter prospective cohort of civil servants designed to assess the determinants of chronic diseases, especially cardiovascular diseases and type 2 diabetes. The present article describes the main design and implementation points of the ELSA-Brasil biobank project. Economic, political, logistical and technological aspects of this study are characterized. Additionally, it discusses the final biorepository protocol and the facilities implemented to achieve this objective. The design and implementation process of the ELSA-Brasil biobank took three years to be performed. Both the central and local biobanks were built according to the best biorepository techniques, using different technological solutions for the distinct needs expected in this study.
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Adulto , Humanos , Bancos de Muestras Biológicas/organización & administración , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus/diagnóstico , Bancos de Muestras Biológicas/normas , Brasil , Enfermedad Crónica , Diseño de Investigaciones Epidemiológicas , Estudios Multicéntricos como Asunto , Estudios ProspectivosRESUMEN
O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) é um estudo de coorte multicêntrico com o objetivo de identificar os fatores de risco associados ao diabetes tipo 2 e à doença cardiovascular na população brasileira. O artigo descreve as estratégias de coleta, processamento, transporte e de controle de qualidade dos exames de sangue e urina no ELSA. O estudo optou pela centralização dos exames em um único laboratório. O processamento das amostras foi realizado nos laboratórios locais, reduzindo o peso do material a ser transportado e diminuindo os custos do transporte para o laboratório central no Hospital da Universidade de São Paulo. O estudo incluiu exames para avaliação de diabetes, resistência à insulina, dislipidemias, alterações eletrolíticas, hormônios tireoidianos, ácido úrico, alterações de enzimas hepáticas, inflamação e hemograma completo. Além desses exames, foram estocados DNA de leucócitos, amostras de urina, plasma e soro. O laboratório central realizou aproximadamente 375.000 exames.
The ELSA (Estudo Longitudinal de Saúde do Adulto - Brazilian Longitudinal Study for Adult Health) is a multicenter cohort study which aims at the identification of risk factors associated with type 2 diabetes and cardiovascular diseases in the Brazilian population. The paper describes the strategies for the collection, processing, transportation, and quality control of blood and urine tests in the ELSA. The study decided to centralize the tests at one single laboratory. The processing of the samples was performed at the local laboratories, reducing the weight of the material to be transported, and diminishing the costs of transportation to the central laboratory at the Universidade de São Paulo Hospital. The study included tests for the evaluation of diabetes, insulin resistance, dyslipidemia, electrolyte abnormalities, thyroid hormones, uric acid, hepatic enzyme abnormalities, inflammation, and total blood cell count. In addition, leukocyte DNA, urine, plasma and serum samples were stored. The central laboratory performed approximately 375,000 tests.
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Adulto , Humanos , Laboratorios/organización & administración , Manejo de Especímenes/métodos , Transportes/métodos , Brasil , Enfermedades Cardiovasculares/diagnóstico , /diagnóstico , Estudios Longitudinales , Estudios Multicéntricos como AsuntoRESUMEN
ABSTRACT: The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy.
Asunto(s)
Espironolactona , Clonidina , Quimioterapia , HipertensiónRESUMEN
Noonan syndrome (NS) is an autosomal dominant disorder, with variable phenotypic expression, characterized by short stature, facial dysmorphisms and heart disease. Different genes of the RAS/MAPK signaling pathway are responsible for the syndrome, the most common are: PTPN11, SOS1, RAF1, and KRAS. The objective of this study was to report a patient with Noonan syndrome presenting mutations in two genes of RAS/MAPK pathway in order to establish whether these mutations lead to a more severe expression of the phenotype. We used direct sequencing of the PTPN11, SOS1, RAF1, and KRAS genes. We have identified two described mutations in heterozygosity: p.N308D and p.R552G in the genes PTPN11 and SOS1, respectively. The patient has typical clinical features similar to the ones with NS and mutation in only one gene, even those with the same mutation identified in this patient. A more severe or atypical phenotype was not observed, suggesting that these mutations do not exhibit an additive effect.
A síndrome de Noonan (SN) é uma doença gênica autossômica dominante, com expressão clínica variável, caracterizada por baixa estatura, dismorfismos faciais e cardiopatia. Diferentes genes da via de sinalização RAS/MAPK são responsáveis pela síndrome, sendo as mais frequentes: PTPN11, SOS1, RAF1 e KRAS. O objetivo deste estudo foi relatar um paciente com SN que apresenta mutações em dois genes da via RAS/MAPK a fim de estabelecer se essas mutações levam a uma expressão mais grave do fenótipo. Utilizou-se sequenciamento direto dos genes PTPN11, SOS1, RAF1 e KRAS. Foram identificadas duas mutações em heterozigose previamente descritas: p.N308D e p.R552G nos genes PTPN11 e SOS1, respectivamente. A paciente apresenta quadro clínico típico semelhante ao dos pacientes com SN e mutação em um único gene, mesmo naqueles com a mesma mutação identificada na paciente. Não foi observado um fenótipo mais grave ou atípico na paciente, sugerindo que as mutações não apresentam um efeito aditivo.
Asunto(s)
Niño , Femenino , Humanos , Mutación , Síndrome de Noonan/genética , Fenotipo , /genética , Proteína SOS1/genética , Heterocigoto , Análisis de Secuencia de ADNRESUMEN
OBJETIVO: Determinar as medidas ecocardiográficas de referência das cavidades cardíacas, da massa e dos índices de massa do ventrículo esquerdo (VE) em amostra da população adulta assintomática. MÉTODOS: Estudo observacional realizado em amostra aleatória da população da cidade de Vitória, Brasil. Foi realizado ecocardiograma transtorácico em 295 indivíduos voluntários (61,7 por cento mulheres), sem história pregressa de doença cardiovascular. Os diâmetros dos ventrículos, a espessura do septo interventricular e da parede posterior do VE, a massa e os índices de massa VE e os diâmetros da aorta e do átrio esquerdo foram avaliados por ecocardiograma unidimensional. As medidas foram descritas por média e desvio padrão, por percentis, com intervalo de confiança de 95 por cento. RESULTADOS: Sexo e idade influenciaram discretamente os valores ecocardiográficos. Em geral, os valores das medidas cardíacas foram maiores no sexo masculino. A espessura da parede posterior, os índices de massa corrigidos pela altura e o diâmetro diastólico foram influenciados pela idade. Os valores de percentil de 95 por cento de septo interventricular e parede posterior do VE para homens foram 9,9 mm e 9,6 mm, respectivamente, e 9,3 mm para septo e parede posterior para mulheres. CONCLUSÃO: Os valores do percentil de 95 por cento do septo interventricular e da parede posterior e, conseqüentemente, de massa ventricular esquerda absoluta e indexada encontrados em nosso estudo na população de Vitória são inferiores aos valores encontrados em estudos prévios. Nesse aspecto, os resultados deste estudo serão úteis como referência, pois estão de acordo com os novos limites sugeridos na literatura para o diagnóstico ecocardiográfico de hipertrofia ventricular esquerda.
OBJECTIVE: To determine echocardiographic reference values for cardiac chambers, left ventricular mass, and left ventricular (LV) mass indexes in an asymptomatic adult population sample. METHODS: This was an observational study based on a randomly selected population sample from the city of Vitória, Brazil. Two hundred and ninety-five volunteers (61.7 percent women) with no past history of cardiovascular disease underwent transthoracic echocardiography. The following M-mode echocardiographic parameters were measured: ventricular diameters, interventricular septal thickness, LV posterior wall thickness, LV mass, left ventricular mass indexes, plus aortic and left atrial diameters. Values were expressed as mean and standard deviation and percentiles, with a 95 percent confidence interval. RESULTS: Echocardiographic values were slightly influenced by gender and age. Overall, cardiac measurements were higher in the male gender. LV posterior wall thickness, mass indexes corrected for height and diastolic diameter were influenced by age. The 95 percent percentiles of interventricular septum and LV posterior wall were 9.9 mm and 9.6 mm for men, respectively, and 9.3 mm for septum and posterior wall for women. CONCLUSION: The 95 percent percentile values of interventricular septum and posterior wall and, therefore, of both absolute and indexed left ventricular mass found in our study conducted in the Vitória population are lower than those reported in previous studies. In this framework, our results will be useful as a reference, since they are consistent with the new limits suggested in the literature for the echocardiographic diagnosis of left ventricular hypertrophy.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ventrículos Cardíacos , Tabique Interventricular , Distribución por Edad , Factores de Edad , Brasil , Ecocardiografía , Métodos Epidemiológicos , Ventrículos Cardíacos/anatomía & histología , Valores de Referencia , Distribución por Sexo , Factores Sexuales , Tabique Interventricular/anatomía & histologíaRESUMEN
Foram submetidos a raçäo padräo de laboratório 16 ratos e outros 16 receberam nutriçäo parenteral total (NPT) por via oral, durante 14 dias. Os animais de ambos os grupos ganharam peso, sem diferença estatística. Na necrópsia retirava-se o segmento intestinal a partir do piloro até a valva ileocecal. Näo houve diferença no comprimento do intestino delgado em ambos os grupos. Porém, o intestino dos animais alimentados com NTP apresentaram diminuiçäo significante de peso comparado com o grupo controle, independentemente da presença ou näo de conteúdo. A resistência intestinal era menor no grupo NTP comparado ao controle, sendo mais significante no íleo. A altura dos vilos, a profundidade das criptas e a extensäo da parede eram significantemente menores no íleo no grupo NTP comparado ao controle. Este achado foi observado também no jejuno, mas sem diferença significante. Conclui-se que nos ratos alimentados com NTP o intestino delgado perde massa e torna-se menos resistente, principalmente no íleo, apesar da manutençäo do estado nutricional. A perda de massa aparece näo apenas na mucosa mas em toda a parede intestinal
Asunto(s)
Humanos , Masculino , Ratas , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Nutrición Parenteral , Ratas Wistar , Resistencia a la TracciónRESUMEN
We report the case of a 7-year-old male child diagnosed with Williams-Beuren syndrome and arterial hypertension refractory to clinical treatment. The diagnosis was confirmed by genetic study. Narrowing of the descending aorta and stenosis of the renal arteries were also diagnosed. Systemic vascular alterations caused by deletion of the elastin gene may occur early in individuals with Williams-Beuren syndrome, leading to the clinical manifestation of systemic arterial hypertension refractory to drug treatment