Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.

Estimating the burden of disease attributable to high blood pressure in South Africa in 2000

Objectives To estimate the burden of disease attributable to high blood pressure (BP) in adults aged 30 years and older in South Africa in 2000. Design World Health Organization comparative risk assessment (CRA) methodology was followed. Mean systolic BP (SBP) estimates by age and sex were obtained from the 1998 South African Demographic and Health Survey adult data. Population-attributable fractions were calculated and applied to revised burden of disease estimates for the relevant disease categories for South Africa in 2000. Monte Carlo simulation modelling techniques were used for uncertainty analysis. Setting South Africa Subjects Adults aged 30 years and older. Outcome measures Mortality and disability-adjusted life years (DALYs) from ischaemic heart disease (IHD), stroke, hypertensive disease and other cardiovascular disease (CVD). Results High BP was estimated to have caused 46 888 deaths (95% uncertainty interval 44 878 - 48 566) or 9% (95% uncertainty interval 8.6 - 9.3%) of all deaths in South Africa in 2000, and 390 860 DALYs (95% uncertainty interval 377 955 - 402 256) or 2.4% of all DALYs (95% uncertainty interval 2.3 - 2.5%) in South Africa in 2000. Overall, 50% of stroke, 42% of IHD, 72% of hypertensive disease and 22% of other CVD burden in adult males and females (30+ years) were attributable to high BP (systolic BP ≥ 115 mmHg). Conclusions High BP contributes to a considerable burden of CVD in South Africa and results indicate that there is considerable potential for health gain from implementing BP-lowering interventions that are known to be highly costeffective.

Incidence of high blood pressure in a group of tannery workers in Brazil

O objetivo deste estudo foi medir a incidência de hipertensão arterial sistêmica em um curtume de médio porte em Botucatu, São Paulo, Sudeste do Brasil, onde havia sido observada, em estudo prévio, uma correlação positiva entre tempo de trabalho e níveis pressóricos, bem como uma alta prevalência de hipertensão. Para tanto, uma coorte de trabalhadores desse curtume foi acompanhada durante sete anos. Ao final do seguimento, estimou-se a taxa de incidência de hipertensão arterial como 0,0964.ano-1, valor considerado elevado se comparado com o encontrado em outros grupos profissionais.

Recovery of high blood pressure after chronic lesions of the commissural NTS in SHR

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A comparison between overweight cutoff points for detection of high blood pressure in adolescents

Objectives: To evaluate the accuracy of three different cutoff points for the detection of high blood pressure in adolescents, given the strong relationship between overweight and high blood pressure levels.Methods: A total of 1,021 adolescents of both sexes were enrolled in the study, selected at random from public and private schools in Londrina, Brazil. Their body weight was measured using a digital balance, and their height with a portable stadiometer with a maximum extension of 2 meters. Arterial blood pressure was measured using an automatic apparatus. The capacity of body mass index to detect high blood pressure was gauged using ROC curves and their parameters (sensitivity, specificity, and area under the curve).Results: The cutoff points proposed in a Brazilian standard exhibited greater accuracy (males: 0.636 +/- 0.038; females: 0.585 +/- 0.043) than the cutoff points proposed in an international (males: 0.594 +/- 0.040; females: 0.570 +/- 0.044) and a North-American standard (males: 0.612 +/- 0.039; females: 0.578 +/- 0.044).Conclusions: The Brazilian proposal offered greatest accuracy for indicating high blood pressure levels.

Independent impact of glycemia ad blood pressure in albuminuria on high-risk subjects for metabolic syndrome

Background: Microalbuminuria may reflect diffuse endothelial damage. Considering that diabetes and hypertension cause vasculopathy, we investigated associations of albumin-to-creatinine ratio (ACR) with plasma glucose and blood pressure levels in high-risk subjects for metabolic syndrome. Methods: A sample of 519 (246 men) Japanese-Brazilians (aged 60 ± 11 years), who participated in a population-based study, had their ACR determined in a morning urine specimen. Backward models of multiple linear regression were created for each gender including log-transformed values of ACR as dependent variable; an interaction term between diabetes and hypertension was included. Results: Macroalbuminuria was found in 18 subjects. ACR mean values for subjects with normal glucose tolerance, impaired fasting glycemia, impaired glucose tolerance and diabetes were 9.9 ± 6.0, 19.0 ± 35.4, 20.7 ± 35.4, and 33.9 ± 55.0 mg/g, respectively. Diabetic subjects showed higher ACR than the others (p < 0.05). An increase in the proportion of albuminuric subjects was observed as glucose metabolism deteriorated (4.9, 17.0, 23.0 and 36.0%). Stratifying into 4 groups according to postchallenge glycemia (< 7.8 mmol/l, n = 9 1; ≥ 7.8 mmol/l, n = 4 10) and hypertension, hypertensive and glucose-intolerant subgroups showed higher ACR values. ACR was associated with gender, waist circumference, blood pressure, plasma glucose and triglyceride (p < 0.05); albuminuric subjects had significantly higher levels of such variables than the normoalbuminuric ones. In the final models of linear regression, systolic blood pressure and 2-hour glycemia were shown to be independent predictors of ACR for both genders (p < 0.05). In men, also waist was independently associated with ACR. No interaction was detected between diabetes and hypertension. Conclusions: These findings suggest that both glucose intolerance and hypertension could have independent but not synergistic effects on endothelial function - reflected by albumin loss in urine. Such hypothesis needs to be confirmed in prospective studies. © 2004 Dustri-Verlag Dr. K. Feistle.

Determinants of blood pressure in type 2 diabetic subjects with high occurrence of inadequate glycemic control

Study design: Association study Objective: To analyze the association between different biological/behavioral risk factors and blood pressure in a sample of type 2 diabetes mellitus patients with poor glycemic control. Methods: A sample of 121 type 2 diabetic patients was selected in the Public Healthcare System in a middle size Brazilian city. Blood pressure was measured using an aneroid device, previously calibrated. Six determinants of blood pressure were taken into count: age, hypoglycemic agents, general obesity, abdominal obesity, eating behaviors and physical activity level. Results: The type 2 diabetic patients presented mean age of 60.1±8.9 years-old and, at least, one risk factor. Eating behaviors (OR adj= 0.31 [0.12-0.75]) and sports practice (OR adj= 0.12 [0.02-0.75]) constituted protective factors associated with lower systolic blood pressure. On the other hand, age was positively associated with high systolic blood pressure (OR adj= 3.81 [1.39-10.38]). Patients with 5-6 risk factors, presented higher values of systolic and (F= 3.857; p= 0.011 [post hoc with p= 0.039]), diastolic blood pressure (F= 4.158; p= 0.008 [post hoc with p= 0.036]) and increased occurrence of hypertension (p= 0.010). Conclusion: Our findings indicate that, behavioral variables were important determinants of blood pressure in type 2 diabetic patients with poor glycemic control and clustering of behavioral and biological risk factors increase the hypertension occurrence.

Prevalence of high blood pressure in Brazilian adolescents and quality of the employed methodological procedures: systematic review

OBJETIVO:Revisar a literatura sobre estudos que estimaram a prevalência de pressão arterial elevada (PAE) ou hipertensão arterial sistêmica (HAS) em adolescentes brasileiros, considerando os procedimentos metodológicos empregados.MÉTODOS:Pesquisa bibliográfica de estudos de prevalência de PAE/HAS em adolescentes de 1995 a 2010. A busca foi realizada nas bases de dados eletrônicos PubMed/Medline, Lilacs, SciELO, Isi e Adolec. Foram utilizados os descritores: hipertensão, pressão arterial, adolescente, estudantes, estudos transversais, prevalência e Brasil, nas línguas portuguesa e inglesa. Além disso, foi elaborado um escore, baseado nas Recommendations for Blood Pressure Measurement in Humans and Experimental Animals e nas VI Diretrizes Brasileiras de Hipertensão, para a análise dos procedimentos utilizados para medida da PA nos estudos variando de 0 a 18.RESULTADOS:Foram identificados 21 artigos, a maioria publicada nos últimos 10 anos, sendo 90,5% realizados em base escolar e nas regiões sudeste, nordeste e sul do país. As prevalências de PAE/HAS variaram de 2,5 a 30,9%. A pontuação dos estudos variou de 0 a 16. Foi observada uma correlação negativa significante (rho = -0,504; p = 0,020) entre a prevalência de PAE/HAS e o escore da qualidade da medida da PA.CONCLUSÃO:A grande variabilidade das estimativas da PAE/HAS parece ser influenciada pelos procedimentos metodológicos utilizados nos estudos.

The Association Between Cardiovascular Risk Factors and High Blood Pressure in Adolescents: A School-Based Study

Objective: Although previous studies have analyzed the association between cardiovascular risk factors and blood pressure in adolescents, few studies conducted in developing countries analyzed whether the aggregation of risk factors contributes to an increased risk of high blood pressure in adolescents. The objective of this study was to assess the association between cardiovascular risk factors (including general overweight, abdominal obesity, high consumption of foods rich in fats, and insufficient physical activity levels) and high blood pressure in adolescents.Methods: This study was carried out from 2007 to 2008 with 1021 adolescents (528 girls) from primary schools located in the city of Londrina- Brazil. Blood pressure was assessed using an oscillometric device. General overweight was obtained through body mass index, abdominal obesity was assessed using waist circumference, and the consumption of foods rich in fat and physical activity were assessed using a questionnaire. The sum of these risk factors was determined.Results: Adolescents with three or four aggregated risk factors were more likely to have higher values of systolic and diastolic blood pressure when compared with adolescents who did not have any cardiovascular risk factors (P = 0.001 for both). Logistic regression indicated that groups of adolescents with 2 (OR = 2.46 [1.11-5.42]; P = 0.026), 3 (OR = 4.97 [2.07-11.92]; P = 0.001) or 4 risk factors (OR = 6.79 [2.24-19.9]; P = 0.001) presented an increased likelihood of high blood pressure.Conclusions: The number of cardiovascular risk factors was found to be related to high blood pressure in adolescents. (C) 2014 Wiley Periodicals, Inc.

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats

Coordenadoria de Aperfeiçoamento em Pesquisa (CAPES)

High blood pressure and sedentary behavior in adolescents are associated even after controlling for confounding factors

The aim of this study was to determine whether high blood pressure (HBP) is associated with sedentary behavior in young people even after controlling for potential confounders (gender, age, socioeconomic level, tobacco, alcohol, obesity and physical activity). In this epidemiological study, 1231 adolescents were evaluated. Blood pressure was measured with an oscillometric device and waist circumference with an inextensible tape. Sedentary behavior (watching television, computer use and playing video games) and physical activity were assessed by a questionnaire. We used mean and standard deviation to describe the statistical analysis, and the association between HBP and sedentary behavior was assessed by the chi-squared test. Binary logistic regression was used to observe the magnitude of association and cluster analyses (sedentary behavior and abdominal obesity; sedentary behavior and physical inactivity). HBP was associated with sedentary behaviors [odds ratio (OR) = 2.21, 95% confidence interval (CI) = 1.41-3.96], even after controlling for various confounders (OR = 1.68, CI = 1.03-2.75). In cluster analysis the combination of sedentary behavior and elevated abdominal obesity contributed significantly to an increased likelihood of having HBP (OR = 13.51, CI 7.21-23.97). Sedentary behavior was associated with HBP, and excess fat in the abdominal region contributed to the modulation of this association.

Evaluation of high-definition and conventional oscillometric blood pressure measurement in anaesthetised dogs using ACVIM guidelines

OBJECTIVES: To evaluate high-definition and conventional oscillometry in comparison with direct blood pressure measurements in anaesthetised dogs. METHODS: Eight simultaneous readings for systolic, diastolic and mean pressure were obtained directly and with each of two devices in nine anaesthetised dogs. Measurement procedure and validation were based on the 2007 ACVIM guidelines. RESULTS: Sixty-three simultaneous readings were evaluated for each device and direct measurements. The mean differences (bias) to direct values were within 10 mmHg for both devices although bias for systolic and diastolic blood pressures was higher for Memodiagnostic. The standard deviations of differences (precision) were within 15 mmHg for Dinamap but exceeded for Memodiagnostic. Correlation coefficients were higher for Dinamap than Memodiagnostic but both failed to reach a correlation of 0.9. Over 50% of values lay within 10 mmHg of direct measures for both devices, but this percentage was greater for Dinamap than Memodiagnostic. Over 80% of values lay within 20 mmHg of direct measures for Dinamap but not for Memodiagnostic. CLINICAL SIGNIFICANCE: Both devices failed to meet ACVIM guideline validation. However, Dinamap only failed with regards to correlation. Memodiagnostic failed on several requirements, and based on poor correlation, accuracy and precision, this device cannot be currently recommended for dogs under anaesthesia.

[Childhood's determinants for high blood pressure in adulthood]

Hypertension has been estimated to affect 20 - 25% of the adult population and represents an important risk factor for cardiovascular disease like coronary heart disease, stroke and peripheral artery occlusive disease. In addition, hypertension supports the development and progression of chronic kidney insufficiency. The interaction of multiple genetic and environmental factors are felt to influence the level of blood pressure. Epidemiological data in the sixties and seventies demonstrated a correlation between cardiovascular disease and infant mortality in the same population. In the late eighties Barker and coworkers described a strong correlation between low birth weight and increased risk for the development of cardiovascular complications. It has been supposed that factors influencing the intrauterine growth and development can lead to adult cardiovascular diseases, known as the concept of "fetal programming". Beside the effect of fetal programming, multiple (preventable and non-preventable) factors determine the blood pressure level in childhood, which will define adult blood pressure level through the blood pressure tracking from childhood to adulthood. Hence, the prevention of cardiovascular disease in adulthood begins in childhood through identification of preventable risk factors as for example obesity and passive smoking and recognition of risk groups like small for gestational age or preterm children.