Serum uric acid is a predictive biomarker of incident metabolic syndrome at the Brazilian longitudinal study of adult Health (ELSA - Brasil).

AIM: To investigate whether serum uric acid (SUA) levels and hyperuricemia can be predictive biomarkers of incident metabolic syndrome(MS) among different body mass index(BMI) categories, and to investigate SUA cutoffs that best discriminate individuals with incident MS. METHODS: We analyzed 7,789 participants without MS at baseline of ELSA-Brasil study. Logistic regression models were performed to evaluate associations between incident MS and SUA levels/hyperuricemia, expressed by odds ratios(ORs) and confidence intervals(95 % CI). RESULTS: We found 1,646 incident MS cases after a median follow-up of 3.8[3.5-4.1] years. Incident MS was present among 8.3 % (n = 290) of participants with normal weight, 28.3 % (n = 850) with overweight, 39.8 % (n = 506) with obesity. Among incident MS participants of total sample, 33.0 % had hyperuricemia [SUA > 6.0 mg/dL (356.9 µmol/L)]. After all adjustments, SUA was independently prognostic of incident MS: for each 1 mg/dL increase in SUA the odds of incident MS were 45 % higher (OR1.45[CI95 %1.34-1.55 p <.01]). Associations were found for those presenting normal weight, overweight and obesity (OR1.43[CI95 %1.31-1.57 p <.01; OR1.22[CI95 %1.13-1.32 p <.01]; and OR1.16[CI95 %1.04-1.29 p <.05]) respectively. Hyperuricemia was independently associated with incident MS (OR1.88[CI95 %1.49-0.2.36 p <.01]). The SUA cut point level maximizing sensitivity and specificity in the discrimination of incident MS was 5.0 mg/dL. CONCLUSIONS: SUA level is an independent predictive biomarker of incident MS at all BMI categories.

Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study.

Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.

Nationwide vitamin D status in older Brazilian adults and its determinants: The Brazilian Longitudinal Study of Aging (ELSI).

Little is known about vitamin D status in older adults in South America, where exposures to ultra-violet radiation are high. We examined the distribution of serum 25-hydroxyvitamin D (25OHD) concentration and its determinants in a nationally representative sample of Brazilians aged 50 years and older. Explanatory variables included environment and individuals' characteristics from the ELSI baseline survey (2015-16). Among the 2,264 participants (mean age = 62.6 years), the geometric mean of 25OHD concentration was 66.8 nmol/L. The prevalence of vitamin D deficiency (< 30 nmol/L) and insufficiency (< 50 nmol/L) were 1.7% (95% CI 1.0, 2.8) and 16% (95% CI 12, 20), respectively. Mean concentrations were lower in those geographical regions situated at lower latitudes. Those at the oldest age, women, self-classified as Black and Brown, living in urban areas and current smokers were more likely to have vitamin D insufficiency, independent of each other and other relevant factors. In contrast, individuals who eat fish regularly were considerably less likely to present lower concentration. Based on these findings it is possible to estimate that about 875,000 older Brazilians have vitamin D deficiency and 7.5 million its insufficiency.

Association between C reactive protein and all-cause mortality in the ELSA-Brasil cohort.

BACKGROUND: High-sensitivity C reactive protein (hsCRP) has been proposed as a marker of incident cardiovascular disease and vascular mortality, and may also be a marker of non-vascular mortality. However, most evidence comes from either North American or European cohorts. The present proposal aims to investigate the association of hsCRP with the risk of all-cause mortality in a multiethnic Brazilian population. METHODS: Baseline data (2008-2010) of a cohort of 14 238 subjects participating in the Brazilian Longitudinal Study of Adult Health were used. hsCRP was assayed with immunochemistry. The association of baseline covariates with all-cause mortality was calculated by Cox regression for univariate model and adjusted for different confounders after a mean follow-up of 8.0±1.1 years. The final model was adjusted for age, sex, self-rated race/ethnicity, schooling, health behaviours and prevalent chronic disease. RESULTS: The risk of death increased steadily by quartiles of hsCRP, from 1.45 (95% CI 1.05 to 2.01) in quartile 2 to 1.95 (95% CI 1.42 to 2.69) in quartile 4, compared with quartile 1. Furthermore, the persistence of a significant graded association after the exclusion of deaths in the first year of follow-up suggests that these results are unlikely to be due to reverse causality. Finally, the HR was unaffected by the exclusion of participants who had self-reported medical history of diabetes, cancer and chronic obstructive pulmonary disease. CONCLUSIONS: Our study shows that hsCRP level is associated with mortality in a highly admixed population, independent of a large set of lifestyle and clinical variables.

Association between diabetes and cognitive function at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA- Brasil).

Diabetes has been associated with cognitive changes and an increased risk of vascular dementia and Alzheimer's disease, but it is unclear whether there are associations between diabetes and early alterations in cognitive performance. The present study consisted of a cross-section analysis of 14,444 participants aged 35-74 years and from a developing country at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil); these participants were recruited between 2008 and 2010. We investigated whether there was an association between diabetes and early changes in the cognitive performance of this Brazilian population. To assess cognitive domains, we used the word-list learning, word-list delayed recall and word recognition tests along. Phonemic verbal fluency tests included semantic phonemic test (animals) and a phonemic test (words beginning with the letter F). Executive functions associated with attention, concentration and psychomotor speed were evaluated using the Trail Making Test B. The exposure variable in the study was defined as diabetes. Multiple linear regression was used to estimate the association between diabetes and cognitive performance. The results were adjusted for age, sex, education, hypertension, coronary disease, depression, physical activity, smoking, alcohol consumption, and the cholesterol/HDL-C ratio. We found a significant association between diabetes and decreased memory, language and executive function (attention, concentration and psychomotor speed) performance in this population from a country with a distinct epidemiological profile, even after adjusting for the main intervening variables.

Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study / Modelo de avaliação da homeostase de resistência à insulina (HOMA-IR) e síndrome metabólica na linha de base de uma coorte brasileira multicêntrica: estudo ELSA-Brasil / Modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) y síndrome metabólico en la línea de base de una cohorte brasileña multicéntrica: estudio ELSA-Brasil

Abstract: Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.

Resumo: O modelo de avaliação da homeostase da resistência à insulina (HOMA-IR) é um método para medir a resistência à insulina. Os pontos de corte do HOMA-IR para identificar a síndrome metabólica podem variar entre as populações e os níveis de índice de massa corporal (IMC). Nosso objetivo foi investigar os pontos de corte do HOMA-IR que melhor discriminam indivíduos com resistência à insulina e com síndrome metabólica para cada categoria de IMC em uma grande amostra de adultos sem diabetes na linha de base do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Entre os 12.313 participantes com média de idade de 51,2 (DP 8,9) anos, a prevalência de síndrome metabólica foi de 34,6%, e 60,1% apresentavam sobrepeso ou obesidade. As prevalências de síndrome metabólica nas categorias de peso normal, sobrepeso e obesidade foram, respectivamente, 13%, 43,2% e 60,7%. O ponto de máxima sensibilidade e especificidade combinadas do HOMA-IR para discriminar a síndrome metabólica foi de 2,35 em toda a amostra, com valores crescentes nas categorias de IMC mais elevadas. Esta investigação contribui para o melhor entendimento dos valores de HOMA-IR associados à resistência à insulina e síndrome metabólica em uma grande amostra de adultos brasileiros, e que o uso de pontos de corte de acordo com a curva ROC pode ser a melhor estratégia. Também sugere que valores diferentes podem ser apropriados nas categorias de IMC.

Resumen: El modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) es un método para medir la resistencia a la insulina. Los cortes HOMA-IR para identificar el síndrome metabólico pueden variar entre las poblaciones y los niveles del índice de masa corporal (IMC). El objetivo fue investigar los cortes de HOMA-IR que mejor discriminaban individuos con resistencia a la insulina y con síndrome metabólico para cada categoría de IMC, en una extensa muestra de adultos sin diabetes en la base de referencia del Estudio Longitudinal de Salud del Adulto (ELSA-Brasil). Entre los 12.313 participantes con una media de edad de 51,2 años (DE 8,9), la prevalencia de síndrome metabólico fue 34,6%, y un 60,1% sufría sobrepeso u obesidad. La prevalencia de síndrome metabólico entre las categorías: peso normal, sobrepeso y obesidad fueron respectivamente, 13%, 43,2% y 60,7%. El punto de máxima sensibilidad combinada y especificidad de HOMA-IR para discriminar el síndrome metabólico fue 2,35 en toda la muestra, con valores crecientes en las categorías de IMC más altas. Esta investigación contribuye a entender mejor los valores HOMA-IR, asociados con resistencia a la insulina y síndrome metabólico en una gran muestra de adultos brasileños, además del planteamiento de que el uso de puntos de corte según la curva ROC es quizás la mejor estrategia a seguir. También sugiere que valores diferentes pueden ser apropiados a través de las categorías de IMC.

Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.

BACKGROUND: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions. OBJECTIVES: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population. METHODS: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs. RESULTS: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals. CONCLUSIONS: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.

Non-HDL-C goals based on the distribution of population percentiles in ELSA-Brasil: Is it time to change?

BACKGROUND AND AIMS: Non-high-density lipoprotein cholesterol (non-HDL-C) goals are defined as 30 mg/dL (0.78 mmol/L) higher than the respective low-density lipoprotein cholesterol (LDL-C) goals. This definition, however, do not consider the population distribution of non-HDL-C, which could represent a more appropriate individual goal when both markers are discordant. The aim of this study is to establish non-HDL-C goals at the same population percentiles of LDL-C. METHODS: Non-HDL-C values were assigned at the same percentiles correspondent to the LDL-C treatment goals for 14,837 participants from the Longitudinal Study of Adult Health (ELSA-Brasil) with triglycerides levels ≤ 400 mg/dL (4.52 mmol/L). We also assessed the frequency of reclassification, defined as the number of subjects with LDL-C levels in the recommended therapeutic category, but with non-HDL-C levels above or below the category. RESULTS: The non-HDL-C values, based on correspondent LDL-C population percentiles, were 92 (2.38), 122 (3.16), 156 (4.04), 191 (4.95), and 223 mg/dL (5.78 mmol/L). Among participants with LDL-C <70 mg/dL (1.81 mmol/L), 22.8% were reclassified in a higher category according to the guidelines-based non-HDL-C cut-off and 30.1% according to the population percentile-based cut-off; 25.6% and 64.1%, respectively, if triglycerides concurrently 150-199 mg/dL (1.69-2.25 mmol/L). CONCLUSIONS: Our results demonstrated that non-HDL-C percentiles-based goals were up to 8 mg/dL (0.21 mmol/L) lower than the guidelines recommended goal and had a profound impact on the reclassification of participants, notably when LDL-C was <100 mg/dL (2.56 mmol/L), the treatment goal for high risk patients. Therefore, non-HDL-C goals should be changed for reduction of residual risk.

Platelet volume is associated with the Framingham risk score for cardiovascular disease in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Platelet volume indices (PVI), an easy and inexpensive surrogate measure of platelet function, have been associated with cardiovascular diseases (CVD) and their risk factors. However, results are conflicting because of the lack of standardized procedures. The purpose of this study is to investigate the relationship of PVI with the Framingham risk score (FRS). METHODS: Baseline data (2008-2010) of 3115 participants enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were used. PVI measurements were strictly controlled. The cohort was distributed according to risk factors and the general FRS was estimated. Multiple linear regression analysis was used to estimate the association between PVI and FRS. RESULTS: Mean platelet volume (MPV), platelet distribution width (PDW) and platelet large cell ratio (P-LCR) independently correlated (p≤0.01) with FRS after adjustment for confounding variables. One unit increase in MPV, PDW, or P-LCR increased the FRS by 0.59%, 0.40%, and 0.08%, respectively. Diabetics had higher (p≤0.004) MPV, PDW, and P-LCR, and hypertensive individuals had higher (p≤0.045) PDW and P-LCR. CONCLUSIONS: Increased PVI was independently correlated with higher CVD risk based on the FRS, diabetes, and systolic hypertension. Prospective follow up of this cohort is warranted to confirm that PVI is associated with the development of CVD.

Chronic kidney disease among adult participants of the ELSA-Brasil cohort: association with race and socioeconomic position.

BACKGROUND: There is increased interest in understanding why chronic kidney disease (CKD) rates vary across races and socioeconomic groups. We investigated the distribution of estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (ACR) and CKD according to these factors in Brazilian adults. METHODS: Using baseline data (2008-2010) of 14,636 public sector employees (35-74 years) enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA)-Brasil multicentre cohort, we estimated the prevalence of CKD by sex, age, race and socioeconomic factors. CKD was defined as ACR ≥ 30 mg/g and/or eGFR < 60 mL/min/1.73 m(2). GFR was estimated by CKD epidemiology collaboration without correction for race. We used logistic regression to estimate the association of race and socioeconomic position (education, income, social class and occupational nature) with CKD after adjusting for sex, age and several health-related factors. RESULTS: The prevalence of high ACR or low eGFR, in isolation and combined, increased with age, and was higher in individuals with lower socioeconomic position and among black individuals and indigenous individuals. The overall prevalence of CKD was 8.9%. After full adjustments, it was similar in men and women (OR=0.90; 95% CI 0.79 to 1.02) and increased with age (OR=1.07; 95% CI 1.06 to 1.08). Compared to white individuals, black individuals (OR=1.23; 95% CI 1.03 to 1.47), 'pardos' (OR=1.16; 95% CI 1.00 to 1.35) and Indigenous (OR=1.72; 95% CI 1.07 to 2.76) people had higher odds for CKD. Having high school (OR=1.15; 95% CI 1.00 to 1.34) or elementary education (OR=1.23; 95% CI 1.03 to 1.47) increased the odds for CKD compared to those having a university degree. CONCLUSIONS: There were marked discrepancies in the increases in reduced eGFR and high ACR with age and race. The higher prevalences of CKD in individuals with lower educational status and in non-whites were not explained by differences in health-related factors.

Standardization and reference intervals of platelet volume indices: Insight from the Brazilian longitudinal study of adult health (ELSA-BRASIL).

Platelet volume indices (PVI) are associated with hematological and non-hematological diseases, notably cardiovascular and cerebrovascular diseases. The establishment of PVI reference intervals (RIs) are essential to evaluate whether these indices are useful in clinical practice. Healthy-associated RIs have not yet been established for the Brazilian population. Here, we determined RIs of PVI for a health adult population, participants of the Brazilian Longitudinal Study of Adult Health ELSA-Brasil. A total of 580 individuals out of an initial sample of 3115 subjects constituted the healthy reference sample. To be part of the study, individuals had to fulfill the following criteria: blood count within 2 hours of collection, no use of continuous medication, self-rated health as good or very good, no reported diagnosis of diabetes and/or arterial hypertension, not smoking, lack of metabolic syndrome, body mass index (BMI) <30 kg/m(2), and platelet, hemoglobin, and creatinine beyond reference values. The RIs are mean platelet volume (MPV): 8.9-11.8 fL, platelet distribution width (PDW): 9.6-15.3 fL, platelet large cell ratio (P-LCR): 15.6-39.5%. These parameters were not significantly affected by age, gender, smoking, obesity, and alcohol abuse. However, significant differences were found among self-rated race/color groups. Standardization of measurement procedures and the establishment of healthy-associated PVI RIs are essential to be able to support clinical decision-making from laboratorial test results. This study at the baseline of the ELSA Brasil reported herein may contribute to future efforts aiming to evaluate whether PVI values are associated with clinical conditions in the Brazilian population.

[Logistics of collection and transportation of biological samples and the organization of the central laboratory in the ELSA-Brasil]. / Logística de coleta e transporte de material biológico e organização do laboratório central no ELSA-Brasil.

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.

[Design and implementation of the ELSA-Brasil biobank: a prospective study in a Brazilian population]. / Delineamento e implementação do biobanco do ELSA-Brasil: estudo prospectivo na população brasileira.

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.

C-reactive protein and B-type natriuretic peptide yield either a non-significant or a modest incremental value to traditional risk factors in predicting long-term overall mortality in older adults.

BACKGROUND: New biomarkers may aid in preventive and end-of-life decisions in older adults if they enhance the prognostic ability of traditional risk factors. We investigated whether C-reactive protein (CRP) and/or B-type natriuretic peptide (BNP) improve the ability to predict overall mortality among the elderly of the Bambuí, Brazil Study of Aging when added to traditional risk factors. METHODS: From 1997 to 2007, 1,470 community-dwelling individuals (≥60 years) were followed-up. Death was ascertained by continuous verification of death certificates. We calculated hazard ratios per 1 standard deviation change (HR) of death for traditional risk factors only (old model), and traditional risk factors plus CRP and/or BNP (new models) and assessed calibration of the models. Subsequently, we compared c-statistic of each of the new models to the old one, and calculated integrated discriminative improvement (IDI) and net reclassification improvement (NRI). RESULTS: 544 (37.0%) participants died in a mean follow-up time of 9.0 years. CRP (HR 1.28, 95% CI 1.17-1.40), BNP (HR 1.31 95% CI 1.19-1.45), and CRP plus BNP (HR 1.26, 95% CI 1.15-1.38, and HR 1.29, 95% CI 1.16-1.42, respectively) were independent determinants of mortality. All models were well-calibrated. Discrimination was similar among the old (c-statistic 0.78 [0.78-0.81]) and new models (p=0.43 for CRP; p=0.57 for BNP; and p=0.31 for CRP plus BNP). Compared to the old model, CRP, BNP, and CRP plus BNP models led to an IDI of 0.009 (p<0.001), -0.005 (p<0.001) and -0.003 (p=0.84), and a NRI of 0.04 (p=0.24), 0.07 (p=0.08) and 0.06 (p=0.10), respectively. CONCLUSIONS: Despite being independent predictors of long-term risk of death, compared to traditional risk factors CRP and/or BNP led to either a modest or non-significant improvement in the ability of predicting all-cause mortality in older adults.

Delineamento e implementacao do biobanco do ELSA-Brasil: estudo prospectivo na populacao brasileira / Design and implementation of the ELSA-Brasil biobank: a prospective study in a Brazilian population

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.

Logistica de coleta e transporte de material biologico e organizacao do laboratorio central no ELSA-Brasil / Logistics of collection and transportation of biological samples and the organization of the central laboratory in the ELSA-Brasil

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.

Ethnic differences in polymorphisms of tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 genes in patients with chronic hepatitis C virus infection.

Ethnic differences in the outcome of hepatitis C have been described. Our aim was to investigate ethnic differences in the distribution of genotypes associated with polymorphisms of the tumor necrosis factor-alpha promoter, interleukin-10 promoter, and transforming growth factor-beta1 leader sequence in patients with hepatitis C. Genomic DNA was obtained from 71 Egyptians and 67 Caucasians (hepatitis C and control patients). Amplification of appropriate gene segments was followed by direct sequencing. Infrequently occurring polymorphisms were identified at positions -244 and -77 of the tumor necrosis factor-alpha promoter and at positions -851 and -657 of the interleukin-10 promoter. The G/A genotype associated with tumor necrosis factor-alpha promoter positions -376 and -244 was more frequent in Egyptians (P =0.001 and P =0.004, respectively). The -244 G/A genotype occurred only in healthy Egyptians (P =0.024). Thus, ethnic differences in the distribution of genotypes of the tumor necrosis factor-alpha promoter exist, which may have clinical implications on the outcome of hepatitis C.

The Bambuí Health and Aging Study (BHAS): private health plan and medical care utilization by older adults.

The aim of this cross sectional study was to investigate whether holding a private health plan affects the consumption of medical services (hospitalization and visits to a doctor) and use of medications by older adults. All residents in Bambuí town (Minas Gerais, Brazil) aged >/= 60 years (n = 1,742) were selected. From these, 92.2% were interviewed and 85.9% were examined (blood tests and physical measurements). After adjustments for worse health status, reported less visits to a doctor, and used a small number of prescribed medications. The main explanation for the aged holding a private health plan was economic, not health. Even though those who had only public health coverage complained more in relation to medical care (70.9%), an important proportion of the aged with a private health care plan presented some kind of complaint (45.2%). Another worrying factor was the difficulty to acquire medication because of financial problems (47.2 and 25.2% reported, respectively). Further investigations are needed to verify whether our results can be generalized to other communities of the country.

Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin.

BACKGROUND/AIMS: In hepatitis C infection, the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect the response to antiviral therapy. Additionally, polymorphisms in the cytokine genes may affect the production of the cytokines. In this study, we determined the frequency of the genotypes associated with polymorphisms of the interleukin-10 and tumor necrosis factor-alpha gene promoters, and transforming growth factor-beta 1 gene leader sequence, and investigated their association with clinical features and the response to interferon-alpha and ribavirin therapy in chronic hepatitis C infection. METHODS: Genomic DNA from 80 patients and 37 racially matched healthy controls was studied by polymerase chain reaction and direct automated sequencing. RESULTS: The interleukin-10 -1082 G/G genotype was identified more frequently in patients than in controls (P=0.048). The transforming-growth factor-beta 1 +29 (codon 10) C/C genotype was associated with resistance to the therapy (P=0.029). After adjusting for potential confounding variables, patients exhibiting the C/C genotype were less likely to respond to treatment than patients with the T/T or T/C genotypes. CONCLUSIONS: These results suggest that inheritance of the interleukin-10 -1082 G/G and the transforming growth factor-beta 1 +29 C/C genotypes, which appear to affect the cytokine production, may be associated with susceptibility to chronic hepatitis C infection and resistance to combined antiviral therapy.