Is there a causal role for homocysteine concentration in blood pressure?:A Mendelian randomization study

Background: An understanding of whether homocysteine is a cause or a marker of increased blood pressure is relevant because blood homocysteine can be effectively lowered by safe and inexpensive interventions (e.g., vitamin B-6, B-9, and B-12 supplementation). Objective: The aim was to assess the causal influence of homocysteine on systolic and diastolic blood pressure (SBP and DBP, respectively) in adults with the use of Mendelian randomization (MR). Design: Data from the 1982 Pelotas Birth Cohort (Brazil) were used. A total of 4297 subjects were evaluated in 2004–2005 (mean age: 22.8 y). The association of homocysteine concentration with SBP and DBP was assessed by conventional ordinary least-squares (OLS) linear regression and 2-stage least-squares (2SLS) regression (MR analysis). The single nucleotide polymorphism (SNP) methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) was used as proxy for homocysteine concentration. We also applied MR to data from the International Consortium for Blood Pressure (ICBP) genomewide association studies (>69,000 participants) using rs1801133 and additional homocysteine-associated SNPs as instruments. Results: In OLS regression, a 1-SD unit increase in log homocysteine concentration was associated with an increase of 0.9 (95% CI: 0.4, 1.4) mm Hg in SBP and of 1.0 (95% CI: 0.6, 1.4) mm Hg in DBP. In 2SLS regression, for the same increase in homocysteine, the coefficients were −1.8 mm Hg for SBP (95% CI: −3.9, 0.4 mm Hg; P = 0.01) and 0.1 mm Hg for DBP (95% CI: −1.5, 1.7 mm Hg; P = 0.24). In the MR analysis of ICBP data, homocysteine concentration was not associated with SBP (β = 0.6 mm Hg for each 1-SD unit increase in log homocysteine; 95% CI: −0.8, 1.9 mm Hg) but was positively associated with DBP (β = 1.1 mm Hg; 95% CI: 0.2, 1.9 mm Hg). The association of genetically increased homocysteine with DBP was not consistent across different SNPs. Conclusion: Overall, the present findings do not corroborate the hypothesis that homocysteine has a causal role in blood pressure, especially in SBP

Prevalência de níveis pressóricos elevados em escolares de Cuiabá, Mato Grosso

OBJECTIVE: The ways in which basal blood pressure levels are obtained may lead to different prevalence estimates. The objective of the study was to estimate the prevalence of high blood pressure among schoolchildren and to compare systolic and diastolic means obtained from three measurements of arterial pressure. METHODS: This was a cross-sectional study among seven to ten-year-old schoolchildren (N=601) from public and private schools in the urban area of Cuiabá, midwestern Brazil, in 2005. Three different blood pressure measurements at ten-minute intervals were made during a single visit. Children were considered to have high blood pressure when their systolic and/or diastolic blood pressure reached levels greater than or equal to the 95th percentile in the reference table, in accordance with their gender, age and percentile height. To calculate the prevalence, the first and third blood pressure measurements were considered separately. RESULTS: There were statistically significant differences between the systolic and diastolic means from the three measurements of the study. The mean systolic and diastolic pressures from the third measurement of the study were 97.2 mmHg (SD=8.68) and 63.1 mmHg (SD=6.66) respectively. The prevalence of high blood pressure was 8.7% (95% CI: 6.4;10.9) from the first measurement and 2.3% (95% CI: 1.1;3.5) from the third measurement. There was no statistical difference in prevalence in relation to age, sex, skin color and type of school. CONCLUSIONS: In studies with a single visit, blood pressure measurements decrease significantly from the first to the third measurement. The third measurement seems to reveal blood pressure levels closer to the basal levels.OBJETIVO: As formas de obtenção dos níveis pressóricos basais podem levar a diferentes estimativas de prevalência. O objetivo do estudo foi estimar a prevalência de níveis pressóricos elevados em escolares e comparar médias sistólicas e diastólicas obtidas após três aferições da pressão arterial. MÉTODOS: Estudo transversal, com escolares entre sete e dez anos (N=601), de escolas públicas e privadas da zona urbana de Cuiabá-MT, Brasil, em 2005. A pressão arterial foi aferida três vezes, com intervalo de dez minutos, em visita única. Consideraram-se crianças com níveis pressóricos elevados as que, segundo sexo, idade e percentil de estatura, atingiram pressão sistólica e/ou diastólica maiores ou iguais ao percentil 95 da tabela de referência. Para o cálculo de prevalência, foram considerados separadamente os níveis pressóricos da primeira e terceira medidas. RESULTADOS: Houve diferença estatisticamente significante entre as médias sistólicas e diastólicas nas três medidas do estudo. A pressão sistólica e diastólica média, utilizando a terceira medida do estudo foi de 97,2 (DP=8,68) mmHg e 63,1 (DP=6,66) mmHg, respectivamente. A prevalência de níveis pressóricos elevados foi de 8,7% (IC 95%: 6,4;10,9) na primeira medida e 2,3% (IC 95%: 1,1;3,5) na 3ª medida. Não houve diferença estatística entre as prevalências com relação à idade, sexo, cor da pele e tipo de escola. CONCLUSÕES: A pressão arterial, em estudos de visita única, diminui significativamente entre a primeira e terceira aferição. A terceira medida parece revelar níveis pressóricos mais próximos dos basais

Impact of stressful life events on central adiposity in the Pelotas Birth Cohort

OBJECTIVE: To investigate how stressful life events and social support relate to central adiposity in Southern Brazil. METHODS: Data included information from 802 participants in the 1982 Pelotas Birth Cohort that was collect in 2004–2005 and 2006. Stratifying by sex, we studied self-reported stressful life events during the year before 2004–2005 in relation to change in waist circumference between 2004–2005 and 2006 and waist-to-hip ratio in 2006, using both bivariate and multivariate linear regression models. RESULTS: In adjusted models, the experience of stressful life events during the year before 2004–2005 predicted a change in waist circumference in 2006 in men and a change in both waist-to-hip ratio in 2006 and waist circumference between 2004–2005 and 2006 in women. Men who experienced two or more stressful events had on average a one centimeter increase in their waist circumference between 2004–2005 and 2006 (β = 0.97, 95%CI 0.02–1.92), compared to those reporting no stressful events. For women, those who had one and those who had two or more stressful life events had over a 1 cm increase in their waist circumference from 2004–2005 to 2006 (β = 1.37, 95%CI 0.17–2.54; β = 1.26, 95%CI 0.11–2.40, respectively), compared to those who did not experience any stressful event. For both sexes, social support level was not significantly related to either waist-to-hip ratio or change in waist circumference, and it did not modify the association between stress and central adiposit

Metodologia do estudo da coorte de nascimentos de 1982 a 2004-5, Pelotas, RS

OBJECTIVE: To describe the methods employed in the longitudinal and follow-up studies of children born in Pelotas (Southern Brazil) in 1982. METHODS: The cohort began with a perinatal health survey that included all 6,011 children born in maternity wards in Pelotas in 1982. The 5,914 children born alive in the city were included in the follow-up studies. By 2004-5, we had conducted eight follow-ups, which consisted of the administration of questionnaires to mothers and/or cohort members, depending on age, in addition to anthropometric and clinical examination. Cohort subjects are described in terms of demographic, socioeconomic, and health-related variables collected during early follow-up studies, which are used as exposure variables. RESULTS: The majority of subjects in the cohort were followed for 23 years and on multiple occasions. The most successful follow-ups were those preceded by a city census. Using this method, we were able to locate 87.2% of subjects in 1984 (mean age 19 months), 84.1% in 1986 (mean age 43 months), and 77.4% in 2004-5, and 77.4% in 2004-5 (mean age 23 years). CONCLUSIONS: Birth cohort studies can be carried out successfully in developing countries, and the methods employed in this life-cycle study have allowed us to investigate the influence of early exposures in determining disease outcomes in adult life.OBJETIVO: Describir los métodos utilizados en el estudio longitudinal y acompañamiento de los niños nacidos en Pelotas (Sur de Brasil) en 1982. MÉTODOS: La cohorte fue iniciada con una investigación de salud perinatal de todos los 6.011 niños nacidos en las maternidades de Pelotas en 1982. Los 5.914 niños nacidos vivos fueron incluidos en los estudios de acompañamiento. Hasta 2004-5 fueron realizados ocho acompañamientos, con la aplicación de cuestionarios a las mamás y/o a los miembros de la cohorte conforme el rango de edad. Exámenes antropométricos y clínicos fueron realizados en las visitas. Los participantes de la cohorte son descritos de acuerdo con las variables demográficas, socioeconómicas y de salud, obtenidas en los primeros acompañamientos, que son utilizadas como variables de exposición. RESULTADOS: La mayor parte de los jóvenes de la cohorte fueron acompañados durante 23 años de vida y distintas visitas. Los acompañamientos que obtuvieron mayor éxito fueron aquellos precedidos por un censo de la ciudad. Con éste método fueron localizados 87,2% en 1984 (edad promedio de 19 meses), 84,1% en 2006 (promedio 43 meses), y 77,4% en 2004-5 (promedio 23 años). CONCLUSIONES: Estudios de cohorte de nacimientos pueden ser realizados con éxito en países en desarrollo, y la metodología utilizada en esos estudios de ciclo vital permite estudiar la influencia de exposiciones precoces sobre la determinación de las enfermedades de la vida adulta.OBJETIVO: Descrever os métodos utilizados no estudo longitudinal e acompanhamento das crianças nascidas em Pelotas (RS) em 1982. MÉTODOS: A coorte foi iniciada com um inquérito de saúde perinatal de todas as 6.011 crianças nascidas nas maternidades de Pelotas em 1982. As 5.914 crianças nascidas vivas foram incluídas nos estudos de acompanhamento. Até 2004-5 foram realizados oito acompanhamentos, com a aplicação de questionários às mães e/ou aos membros da coorte, conforme a faixa etária. Exames antropométricos e clínicos foram realizados nas visitas. Os participantes da coorte são descritos conforme variáveis demográficas, socioeconômicas e de saúde colhidas nos primeiros acompanhamentos, que são utilizadas como variáveis de exposição. RESULTADOS: A maior parte dos jovens da coorte foram acompanhados durante 23 anos de vida e distintas visitas. Os acompanhamentos que obtiveram maior êxito foram aqueles precedidos por um censo da cidade. Com este método foram localizados 87,2% em 1984 (idade média de 19 meses), 84,1% em 2006 (média 43 meses), e 77,4% em 2004-5 (média 23 anos). CONCLUSÕES: Estudos de coorte de nascimentos podem ser realizados com sucesso em países em desenvolvimento, e a metodologia empregada nesses estudos de ciclo vital permite estudar a influência de exposições precoces sobre a determinação das doenças da vida adulta

Educação e trabalho na coorte de nascimentos de 1982 a 2004-5, Pelotas, RS

OBJECTIVE: To analyze the influence of biological and socioeconomic factors throughout life on entry into the university and insertion in the work force of young adults from the 1982 birth cohort. METHODS: Longitudinal study of 5,914 births that took place in the city of Pelotas, Southern Brazil, in 1982. Data was collected by means of questionnaires applied on young adults when accompanying the 1982 cohort in 2004-5. Information was gathered concerning educational level and insertion in the labor market. Poisson Regression was utilized to study the effect of demographic and socioeconomic variables, as well as birth weight and maternal breastfeeding, on the outcomes. RESULTS: On the average, these young adults had 9.4 (± 3.1) years of schooling and 42% of them were attending school in 2004-5. One in five young adults had entered a university and approximately two thirds were working during the month prior to the interview. Entry in the university was determined by economic conditions. Furthermore, women's birth weight and breastfeeding among men influenced this outcome. Insertion in the labor market was more frequent among the poorer men, but this did not affect women's outcomes in this respect. CONCLUSIONS: The low inclusion in the university and the need to enter the labor market among the poor families maintains a vicious circle that reproduces the dominant social hierarchy.OBJETIVO: Analizar la influencia de factores socioeconómicos y biológicos precoces a lo largo de la vida sobre el ingreso en la universidad y la inserción en el mercado de trabajo de los jóvenes de la cohorte de nacimiento de 1982. MÉTODOS: Estudio longitudinal de 5.914 nacimientos de la ciudad de Pelotas (Sur de Brasil), en 1982. Utilizándose cuestionarios aplicados al joven, fueron colectadas informaciones sobre el nivel educacional y la inserción en el mercado de trabajo durante acompañamiento de la cohorte realizado en 2004-5. Regresión de Poisson fue utilizada para estudiar el efecto de las variables demográficas, socioeconómicas, peso al nacer y amamantamiento materno sobre los desenlaces. RESULTADOS: La escolaridad promedio fue de 9,4 años (± 3,1) y 42% de los jóvenes estaban frecuentando la escuela en 2004-5. Uno de cada cinco jóvenes había ingresado en la universidad y cerca de dos tercios estaban trabajando en el mes anterior a la entrevista. El ingreso en la universidad fue determinado por las condiciones económicas, y tuvo influencia de peso al nacer en las mujeres y del amamantamiento en los hombres. La inserción en el mercado de trabajo fue más frecuente entre los hombres más pobres, pero no para las mujeres. CONCLUSIONES: La baja inclusión universitaria y la necesidad de inserción en el mercado de trabajo de los jóvenes de familias más pobres mantienen un círculo vicioso que reproduce la jerarquía social dominante.OBJETIVO: Analisar a influência de fatores socioeconômicos e biológicos precoces ao longo da vida sobre o ingresso na universidade e a inserção no mercado de trabalho dos jovens da coorte de nascimento de 1982. MÉTODOS: Estudo longitudinal de 5.914 nascimentos da cidade de Pelotas (RS), em 1982. Utilizando-se questionários aplicados ao jovem, foram coletadas informações sobre nível educacional e a inserção no mercado de trabalho durante acompanhamento da coorte realizado em 2004-5. Regressão de Poisson foi utilizada para estudar o efeito de variáveis demográficas, socioeconômicas, peso ao nascer e aleitamento materno sobre os desfechos. RESULTADOS: A escolaridade média foi de 9,4 anos (± 3,1) e 42% dos jovens estavam freqüentando a escola em 2004-5. Um de cada cinco jovens havia ingressado na universidade e cerca de dois terços estavam trabalhando no mês anterior à entrevista. O ingresso na universidade foi determinado pelas condições econômicas, e teve influência do peso ao nascer nas mulheres e da amamentação nos homens. A inserção no mercado de trabalho foi mais freqüente entre os homens mais pobres, mas não para as mulheres. CONCLUSÕES: A baixa inclusão universitária e a necessidade de inserção no mercado de trabalho dos jovens de famílias mais pobres mantêm um círculo vicioso que reproduz a hierarquia social dominante

Are consumption of dairy products and physical activity independently related to bone mineral density of 6-year-old children? Longitudinal and cross-sectional analyses in a birth cohort from Brazil.

OBJECTIVE: To evaluate cross-sectional and longitudinal associations of consumption of dairy products and physical activity (PA) with bone mineral density (BMD). DESIGN: Cohort study with children from the 2004 Pelotas (Brazil) Birth Cohort. SETTING: Pelotas, a medium-sized Brazilian city. SUBJECTS: The study started in 2004 and mothers/children were interviewed/measured periodically from birth to age 6 years. PA was measured by maternal proxy at 4 and 6 years and by accelerometry at 6 years. Consumption of dairy products was measured using 24 h food recall (at 4 years) and FFQ (at 6 years). Total-body and lumbar-spine BMD (g/cm2) were measured by dual-energy X-ray absorptiometry. RESULTS: At 6 years, BMD was measured in 3444 children and 2636 children provided data on objectively measured PA by accelerometry. Consumption of dairy products at 4 years was associated with higher lumbar-spine BMD at 6 years in boys, while current consumption was positively associated with BMD in both sexes (P < 0·001). PA assessed by maternal report at 4 and 6 years of age was associated with higher BMD at 6 years in boys. PA assessed by accelerometry was positively related to total-body and lumbar-spine BMD in boys and lumbar-spine BMD in girls. We did not find evidence for an interaction between PA and consumption of dairy products on BMD. CONCLUSIONS: We observed positive and independent longitudinal and cross-sectional associations between consumption of dairy products and PA with BMD in the total body and at the lumbar spine in young children

The Pelotas birth cohort study, Rio Grande do Sul, Brazil, 1982-2001:Estudo de coorte de nascimentos em Pelotas, Rio Grande do Sul, Brasil, 1982-2001

Given the growing recognition of the importance of the life course approach for the determination of chronic diseases, birth cohort studies are becoming increasingly important. This paper describes the methods used in the 1982 Pelotas (Brazil) birth cohort study, one of the largest and longest studies of this type in developing countries. All 5,914 hospital births occurring in Pelotas in 1982 (over 99% of all deliveries) were studied prospectively. The main stages of the study took place in 1983, 1984, 1986, 1995, 1997, 2000, and 2001. More than two thousand variables are available for each subject who participated in all stages of the study. Recent phases of the study included the examination of 2,250 males when presenting for the army recruitment exam in 2000, the study of a 27% sample of men and women in 2001 through household visits, and the study of over 400 children born to the cohort women. Follow-up rates in the recent stages of the cohort were 78.9% for the army examination and 69.0% for the household visits. Ethnographic and oral health studies were conducted in sub-samples. Some recent results on blood pressure, adolescent pregnancy, and asthma are presented as examples of utilization of the data. Suggestions on lessons learned for other cohort studies are proposed