José Geraldo Mill

Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): Objectives and Design

Although low- and middle-income countries still bear the burden of major infectious diseases, chronic noncommunicable diseases are becoming increasingly common due to rapid demographic, epidemiologic, and nutritional transitions. However, information is generally scant in these countries regarding chronic disease incidence, social determinants, and risk factors. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information with respect to the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes. In this report, the authors delineate the studys objectives, principal methodological features, and timeline. At baseline, ELSA-Brasil enrolled 15,105 civil servants from 5 universities and 1 research institute. The baseline examination (2008-2010) included detailed interviews, clinical and anthropometric examinations, an oral glucose tolerance test, overnight urine collection, a 12-lead resting electrocardiogram, measurement of carotid intima-media thickness, echocardiography, measurement of pulse wave velocity, hepatic ultrasonography, retinal fundus photography, and an analysis of heart rate variability. Long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes. Annual telephone surveillance, initiated in 2009, will continue for the duration of the study. A follow-up examination is scheduled for 2012-2013.

Cohort Profile: Longitudinal Study of Adult Health (ELSA-Brasil)

Chronic diseases are a global problem, yet information on their determinants is generally scant in low- and middle-income countries. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information regarding the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes, in one such setting. At Visit 1, we enrolled 15 105 civil servants from predefined universities or research institutes. Baseline assessment (2008–10) included detailed interviews and measurements to assess social and biological determinants of health, as well as various clinical and subclinical conditions related to diabetes, cardiovascular diseases and mental health. A second visit of interviews and examinations is under way (2012–14) to enrich the assessment of cohort exposures and to detect initial incident events. Annual surveillance has been conducted since 2009 for the ascertainment of incident events. Biological samples (sera, plasma, urine and DNA) obtained at both visits have been placed in long-term storage. Baseline data are available for analyses, and collaboration via specific research proposals directed to study investigators is welcome.

Hipertensão arterial e consumo de sal em população urbana

OBJETIVO: Avaliar o consumo de sal e a relacao sodio/potassio urinario em amostra randomizada de populacao urbana etnicamente miscigenada. METODOS: Foi selecionada uma amostra randomica de 2.268 residentes de Vitoria, ES, entre 25 e 64 anos de idade. Os individuos foram escolhidos por amostragem domiciliar realizada em 1999/2000, dos quais 1.663 (73,3%) compareceram ao hospital para a realizacao de exames padronizados. O consumo estimado de sal, Na+ e K+ foi determinado por meio da coleta de urina de 12h no periodo noturno (19h as 7h) e do gasto mensal de sal domiciliar referido durante a entrevista. A pressao arterial clinica foi medida duas vezes por diferentes pesquisadores treinados em condicoes padronizadas, usando esfignomamometro de mercurio. Para analise estatistica foram utilizados o teste de Student e o teste de Tukey. RESULTADOS: A excrecao urinaria de Na+ foi mais alta em homens e em individuos de menores condicoes socioeconomicas (P<0,000). Nao foi observada diferenca entre os grupos etnicos. A excrecao de K+ nao se relacionou com nivel socioeconomico e raca, mas foi significativamente mais alta entre os homens (25±18 x 22±18 mEq/12h; P=0,002). Foi observada uma correlacao linear positiva entre a excrecao urinaria de Na+ e pressao arterial sistolica (r=0,15) e diastolica (r=0,19). Individuos hipertensos apresentaram maior excrecao urinaria de Na+ e relacao Na/K, quando comparados com individuos normotensos. O consumo de sal relatado foi aproximadamente 50% do consumo estimado pela excrecao urinaria de 12h (em torno de 45% da excrecao urinaria de 24h). CONCLUSOES: A ingestao de sal e fortemente influenciada pelo nivel socioeconomico e pode, parcialmente, explicar a alta prevalencia de hipertensao arterial nas classes socioeconomicas mais baixas.

β2 Adrenoceptor Functional Gene Variants, Obesity, and Blood Pressure Level Interactions in the General Population

Abstract—We investigated the association of &bgr;2 adrenoceptor functional gene variants (Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms), obesity phenotypes, and blood pressure levels in a large, ethnically mixed urban population. The individuals (n=1576) were randomly selected for a cross-sectional study of cardiovascular risk factors in Vitória, Brazil. Statistically significant associations among systolic blood pressure and the Arg16Gly and Thr164Ile variants were identified in univariate analysis. The Gly16/Gly16 genotype was still associated with systolic blood pressure (SBP) in multivariate analysis adjusting for age, gender, ethnicity, total cholesterol, diabetes, and body mass index (BMI) (P =0.01). The Arg16 allele was the only genotypic variable associated with BMI, and, in a dominant model, it remained associated with an increased BMI even after adjustment for age, gender, ethnicity, triglycerides, HDL cholesterol, LDL cholesterol, diabetes, and hypertension status (P =0.02). Although the different polymorphisms did not interact in the determination of SBP, a significant interaction with BMI (P =0.02), not through linkage disequilibrium, was identified between the Gln27Glu and the Thr164Ile variants. Furthermore, a significant interaction among the Arg16Gly polymorphism and BMI (P =0.036) and waist-hip ratio (P =0.003) in determining SBP was disclosed by ANOVA factorial modeling, with SBP used as the dependent variable. An interaction between the Thr164Ile polymorphism and waist-hip ratio was also identified (P =0.018). Finally, multiple logistic regression models showed a 1.48-fold increase in the risk of hypertension in individuals harboring the Gly16/Gly16 genotype and a 1.31-fold (P =0.01) and a 1.49-fold (P =0.003) increased risk of obesity in individuals harboring the Gln27/Gln27 genotype or the presence of the Arg16 allele, respectively. Taken together, these data provide evidence for a strong but complex relation between &bgr;-adrenoceptor gene variants, hypertension, and obesity.

Prevalência de síndrome metabólica em estudo de base populacional, Vitória, ES - Brasil

Metabolic Syndrome (MS) is a complex disorder including several factors predisposing to development of cardiovascular diseases and diabetes. Despite the importance of MS for the health system, the epidemiological characteristics of this condition in the Brazilian population are still scarce. The prevalence of MS as a function of gender, age and socioeconomic level was determined in a population-based study in Vitória, ES, Brazil, by using the NCEP-ATPIII diagnosis criteria. Socioeconomic, biochemical, anthropometric, and hemodynamic data were obtained in 1,663 individuals from a random sample of Vitória population (25-64 y). The estimated prevalence of MS was 29,8% (CI95 = 28-32%). No significant sex-related differences were observed. Prevalence increased from the youngest (26-34 y) to the oldest (55-64 y) group (15.8% and 48.3%, respectively). A progressive increase of MS frequency was observed in women from the higher to the lowest socioeconomic level. The most frequent trait of MS in males was high blood pressure, followed by hypertriglyceridemia, low HDL-c levels, hyperglycemia, and central obesity. In females, hypertension was also the most frequent factor, followed by low HDL-c levels, abdominal obesity, hypertriglyceridemia and hyperglycemia. Our data show that prevalence of MS is high in the studied population, even in the youngest group. Moreover, high blood pressure gives a significant contribution to the diagnosis of this syndrome in both sexes. The precocious control of risk factors is necessary to reduce the impact of cardiovascular morbidity and mortality.

Angiotensinogen 235T Allele “Dosage” Is Associated With Blood Pressure Phenotypes

Abstract—The genetic mechanisms underlying interindividual blood pressure variation among humans may reflect, at least in part, clustering of functional gene variants belonging to complex blood pressure control systems. In this study, we investigated the association of specific functional gene variants of the renin-angiotensin system, ACE (I/D) and angiotensinogen (M/T) genes, with blood pressure phenotypes (systolic, mean, diastolic, and pulse pressure), in an ethnically mixed urban population in Brazil. Individuals (n=1421) were randomly selected from the general population of the Vitoria City Metropolitan area. Neither gender, age, smoking status, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, or diabetes was associated with ACE or AGT polymorphism in univariate analysis. No association was found between ACE variants and blood pressure phenotypes. However, a statistically significant association was revealed between the AGT 235T variant and all blood pressure phenotypes, consistent with an additive/codominant mode of action even after adjustment for age and gender (P <0.01). Genotypic analysis contemplating both ACE and AGT variants in the same model did not show any significant interaction between both genetic polymorphisms. In addition, the AGT 235T allele was significantly associated with hypertension in a recessive model, which remained as an independent risk factor for hypertension even after adjustment for age, gender, and ethnicity (OR, 1.33; 95% CI, 1.04 to 1.70). Taken together, these data indicate a linear relation between AGT 235T allele number (“dosage”) and blood pressure in an ethnically mixed urban population and confirmed its role as an independent risk factor for hypertension for men and women when in homozygosity.

Doenças crônicas não transmissíveis no Brasil: prioridade para enfrentamento e investigação

As Doencas Cronicas Nao Transmissiveis representam a maior carga de morbimortalidade no Brasil. Em 2011, o Ministerio da Saude lancou seu Plano de Acoes Estrategicas para o Enfrentamento das Doencas Cronicas Nao Transmissiveis, enfatizando acoes populacionais para controlar as doencas cardiovasculares, diabetes, câncer e doenca respiratoria cronica, predominantemente pelo controle do fumo, inatividade fisica, alimentacao inadequada e uso prejudicial de alcool. Apesar da producao cientifica significativa sobre essas doencas e seus fatores de risco no Brasil, poucos sao os estudos de coorte nessa tematica. Nesse contexto, o Estudo Longitudinal da Saude do Adulto (ELSA-Brasil) acompanha 15.105 servidores publicos do Pais. Seus dados espelham a realidade brasileira de altas prevalencias de diabetes e hipertensao e dos fatores de risco. A diversidade das informacoes produzidas permitira aprofundar o entendimento causal dessas doencas e subsidiar politicas publicas para seu enfrentamento.Chronic Non-Communicable Diseases are the main source of disease burden in Brazil. In 2011, the Brazilian Ministry of Health launched the Strategic Plan of Action for Management of Chronic Non-Communicable Diseases focusing on population-based interventions to manage cardiovascular diseases, diabetes, cancer, and chronic respiratory diseases mainly through fighting tobacco use, unhealthy diets, physical inactivity and the harmful use of alcohol. Although a significant number of scientific studies on chronic diseases and their risk factors have been undertaken in Brazil, few are of cohort design. In this context, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort study of 15,105 Brazilian public servants reflects the reality of high prevalences of diabetes, hypertension and the main chronic diseases risk factors. The diversity of information that the Study will produce can provide important input to better understand the causes of chronic diseases and to support public policies for fighting them.

Effects of Depression, Anxiety, Comorbidity, and Antidepressants on Resting-State Heart Rate and Its Variability: An ELSA-Brasil Cohort Baseline Study

OBJECTIVE Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. METHOD A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule-Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. RESULTS Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohens d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohens d, 0.42-0.95) and other antidepressants (Cohens d, 0.37-0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. CONCLUSIONS The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

Afericoes e exames clinicos realizados nos participantes do ELSA-Brasil

The article describes assessments and measurements performed in the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil). Some assessments including anthropometric assessment, casual blood pressure measurement, and ankle-brachial index have an established clinical application while others including pulse wave velocity, heart rate variability, and carotid intima-media thickness have no established application and do not have reference values for healthy Brazilian population but may be important predictors of cardiovascular outcomes. Blood pressure measurement following postural change maneuver was included in the ELSA-Brasil because it has not been much tested in epidemiological studies. Innovative approaches were developed for assessing the ankle-brachial index using an automatic device instead of the mercury column to measure blood pressure and for assessing the anterior-posterior diameter of the right lobe of the liver by ultrasound for quantitative assessment of nonalcoholic fatty liver disease. All ELSA-Brasil subjects were younger (35 years or more) than those included in other cohorts studying subclinical atherosclerosis. The inclusion of younger individuals and a variety of assessments make the ELSA-Brasil a relevant epidemiology study nationwide and worldwide.

Racial differences in aortic stiffness in normotensive and hypertensive adults.

OBJECTIVE To investigate whether differences exist in the mechanical properties of large arteries between white and black subjects. DESIGN Eighty-two white (49 normotensive and 33 untreated hypertensive) and 38 black (24 normotensive and 14 untreated hypertensive) adult male volunteers were studied in a cross-sectional study. METHODS Carotid-femoral pulse wave velocity was measured as an index of arterial stiffness, using a recently developed non-invasive automatic device, and compared between white and black subjects before and after the adjustment for age. The slope of regressions for pulse wave velocity and systolic blood pressure were also compared between racial groups. RESULTS In the normotensive group, white subjects presented higher mean values of pulse wave velocity than blacks while the opposite behavior was found in the hypertensive group. After adjustment for age, significant differences in pulse wave velocity between whites and blacks became evident in the normotensive (whites 8.15 +/- 0.04 versus blacks 7.75 +/- 0.02 m/s; P < 0.001) and hypertensive (whites 8.88 +/- 0.02 versus blacks 9.30 +/- 0.17 m/s; P < 0.001) groups. Linear regression analysis for age-adjusted pulse wave velocity and systolic blood pressure showed that the slope was significantly greater in blacks than in whites (0.040 +/- 0.002 versus 0.019 +/- 0.001 m/s; P < 0.001). CONCLUSION These data indicate that there is a greater pressure-dependent increase in aortic stiffness in blacks than in whites. This finding points towards major differences in mechanical properties of large arteries between these racial groups.