Endothelial function in normotensive and high-normal hypertensive subjects

To evaluate the impact of a mild increment in blood pressure level on endothelial function, we evaluated 61 healthy volunteers (24 women, 37 men, and aged 35-50 years). All subjects underwent a blood chemistry panel to exclude any metabolic abnormalities and were submitted to a Doppler ultrasound of the brachial artery to assess endothelial function. We assessed the endothelial response to reactive hyperaemia and exogenous nitric oxide administration considering an increase in systolic blood pressure (SBP) at each 10-mm Hg interval. Our study population was divided as follows: SBP = 115 mm Hg and = 125 mm Hg and = 135 mm Hg and <140 mm Hg (SG4, n = 15). We found a significant difference in flow-mediated dilation among SG2, SG3 and SG4, 16.2 +/- 5.6, 13.4 +/- 5.2 and 11.5 +/- 3.6%, P < 0.05, respectively). After nitrate administration, we observed a nonsignificant decrease in brachial artery dilation among groups, P = 0.217. Our data showed in a healthy normotensive population, without any risk factor for atherosclerotic disease that small increases in SBP but not in diastolic blood pressure may impair endothelial function even in subjects considered as high-normal, meaning that this population deserves more attention than usually ascribed to intervene and prevent complications, as endothelial dysfunction may represent an early change in those who develop hypertension later in life.Universidade Federal de São Paulo, Div Nephrol, Escola Paulista Med, BR-04025011 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, Escola Paulista Med, BR-04025011 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Radiol, Escola Paulista Med, BR-04025011 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Div Nephrol, Escola Paulista Med, BR-04025011 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, Escola Paulista Med, BR-04025011 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Radiol, Escola Paulista Med, BR-04025011 São Paulo, SP, BrazilWeb of Scienc

Efectos de diferentes grados de sensibilidad a la insulina en la función endotelial de pacientes obesos

BACKGROUND: Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. OBJECTIVE: To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. METHODS: Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). RESULTS: We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2±7.0 vs 18.0±7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. CONCLUSION: Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.FUNDAMENTO: La obesidad derivada del depósito de grasa intraabdominal tiende a aumentar la producción de hormonas y citocinas, empeorando la sensibilidad a la insulina y llevando a disfunción endotelial. La hiperinsulinemia es considerada un factor de riesgo independiente para enfermedad isquémica cardíaca y es una causa de disfunción endotelial en individuos sanos. OBJETIVO: Evaluar el impacto de diferentes grados de resistencia a la insulina, medida por el HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre la función endotelial de obesos, pacientes no diabéticos, sin historia previa de eventos cardiovasculares y diversos componentes del síndrome metabólico. MÉTODOS: Un total de 40 individuos obesos fue sometido a medidas antropométricas, presión arterial de consultorio, MAPA y exámenes de laboratorio, además de evaluación ultrasonográfica no invasiva de la función endotelial. Los pacientes fueron divididos en tres grupos de acuerdo con el grado de resistencia a insulina: pacientes con valores de HOMA-IR entre 0,590 y 1,082 fueron incluidos en el Grupo 1 (n = 13); entre 1,083 y 1,410 en el Grupo 2 (n = 14); y entre 1,610 y 2,510 en el Grupo 3 (n = 13). RESULTADOS: Encontramos una diferencia significativa en la vasodilatación mediada por flujo en el Grupo 3 en relación al Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 %, p = 0,006). Hubo una correlación negativa entre la función endotelial e insulina, HOMA-IR y triglicéridos. CONCLUSIÓN: Nuestro estudio sugiere que leves alteraciones en los niveles de resistencia a la insulina evaluada por el HOMA-IR pueden causar algún impacto sobre la función vasodilatadora del endotelio en individuos obesos no complicados con diferentes factores de riesgo cardiovascular.FUNDAMENTO: A obesidade derivada da deposição de gordura intra-abdominal tende a aumentar a produção de hormônios e citoquinas, piorando a sensibilidade a insulina e levando a disfunção endotelial. A hiperinsulinemia é considerada um fator de risco independente para doença isquêmica cardíaca e é uma causa de disfunção endotelial em indivíduos saudáveis. OBJETIVO: Avaliar o impacto de diferentes graus de resistência a insulina, medida pelo HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre a função endotelial de obesos, pacientes não diabéticos, sem história prévia de eventos cardiovasculares e diversos componentes da síndrome metabólica. MÉTODOS: Um total de 40 indivíduos obesos foi submetido a medidas antropométricas, pressão arterial de consultório, MAPA e exames laboratoriais, além de avaliação ultrassonográfica não invasiva da função endotelial. Os pacientes foram divididos em três grupos de acordo com o grau de resistência a insulina: pacientes com valores de HOMA-IR entre 0,590 e 1,082 foram incluídos no Grupo 1 (n = 13); entre 1,083 e 1,410 no Grupo 2 (n = 14); e entre 1,610 e 2,510 no Grupo 3 (n = 13). RESULTADOS: Encontramos uma diferença significativa na vasodilatação mediada por fluxo no Grupo 3 em relação ao Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 %, p = 0,006). Houve uma correlação negativa entre a função endotelial e insulina, HOMA-IR e triglicérides. CONCLUSÃO: Nosso estudo sugere que leves alterações nos níveis de resistência a insulina avaliada pelo HOMA-IR podem causar algum impacto sobre a função vasodilatadora do endotélio em indivíduos obesos não complicados com diferentes fatores de risco cardiovascular.Universidade Federal de São Paulo (UNIFESP) EPMUNIFESP, EPMSciEL

Hyperglycemia and nocturnal systolic blood pressure are associatedwith left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients

BACKGROUND: The aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI) and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes. METHODS: Ninety-one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59 essential hypertensive patients (group-2 [G2]) and 26 healthy controls (group-3 [G3]) were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM) and echocardiography (ECHO) with Doppler. We calculated an average of fasting blood glucose (AFBG) values of G1 from the previous 4.2 years and a glycemic control index (GCI) (percentual of FBG above 200 mg/dl). RESULTS: G1 and G2 did not differ on average of diurnal systolic and diastolic BP. However, G1 presented worse diastolic function and a higher average of nocturnal systolic BP (NSBP) and LVMI (NSBP = 132 ± 18 vs 124 ± 14 mmHg; P < 0.05 and LVMI = 103 ± 27 vs 89 ± 17 g/m(2); P < 0.05, respectively). In G1, LVMI correlated with NSBP (r = 0.37; P < 0.001) and GCI (r = 0.29; P < 0.05) while NSBP correlated with GCI (r = 0.27; P < 0.05) and AFBG (r = 0.30; P < 0.01). When G1 was divided in tertiles according to NSBP, the subgroup with NSBP≥140 mmHg showed a higher risk of LVH. Diabetics with NSBP≥140 mmHg and AFBG>165 mg/dl showed an additional risk of LVH (P < 0.05; odds ratio = 11). In multivariate regression, both GCI and NSBP were independent predictors of LVMI in G1. CONCLUSION: This study suggests that hyperglycemia and higher NSBP levels should be responsible for an increased prevalence of LVH in hypertensive patients with Type 2 DM

Association of urinary 90 kDa angiotensin- converting enzyme with family history of hypertension and endothelial function in normotensive individuals

We described angiotensin-I-converting enzyme (ACE) isoforms with molecular masses of 190, 90, and 65 kDa in the urine of normotensive offspring of hypertensive subjects. Since they did not appear in equal amounts, we suggested that 90 kDa ACE might be a marker for hypertension. We evaluated the endothelial response in normotensive offspring with or without family history of hypertension and its association with the 90 kDa ACE in urine. Thirty-five normotensive subjects with a known family history of hypertension and 20 subjects without a family history of hypertension, matched for age, sex, body weight, and blood pressure, were included in the study. Endothelial function was assessed by ultrasound and a sample of urine was collected for determination of ACE isoforms. In the presence of a family history of hypertension and detection of 90 kDa ACE, we noted a maximal flow mediated dilation of 12.1 ± 5.0 vs 16.1 ± 6.0% in those without a previous history of hypertension and lacking urinary 90 kDa ACE (P < 0.05). In subjects with a family history of hypertension and presenting 90 kDa ACE, there were lower levels of HDL-cholesterol (P < 0.05) and higher levels of triglycerides (P < 0.05). Subjects with 90 kDa ACE irrespective of hypertensive history presented a trend for higher levels of triglycerides and HDL-cholesterol (P = 0.06) compared to subjects without 90 kDa ACE. Our data suggest that the 90 kDa ACE may be a marker for hypertension which may be related to the development of early atherosclerotic changes.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaFundação Oswaldo Ramos Universidade Federal de São Paulo (UNIFESP) e Hospital do Rim e Hipertensão Departamento de RadiologiaUNIFESP, EPM, Depto. de MedicinaFundação Oswaldo Ramos UNIFESP, e Hospital do Rim e Hipertensão Depto. de RadiologiaSciEL

Blood pressure and cardiorenal responses to anti hypertensive therapy in obese women

Objective: Blood pressure(BP) and target organ responses to antihypertensive drugs are not well established in hypertensive obese patients. This study is aimed at evaluating the effects of obesity and adiposity distribution patterns on these responses. Methods: 49 hypertensive obese women were designated to different groups according to waist to hip ratio measurements - 37 with troncular and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine combination therapy to achieve a BP lower than 140/90mmHg. Ambulatory blood pressure monitoring (ABPM), echocardiography, and albuminuria were assessed before and after the intervention. Results: After 24 weeks, weight loss was less than 2% in both groups. ABPM targets were achieved in 81.5% of patients upon a combination of 2(26.5%) or 3(55.1%) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity) / -23.6/-14.9mmHg (peripheral obesity) were obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients. Upon BP control, microalbuminuria was markedly decreased, while only slight decrease in left ventricular mass was observed for both groups. Conclusions: in the absence of weight loss, most patients required combined antihypertensive therapy to control their BP, regardless of their body fat distribution pattern. Optimal target BP and normal albuminuria were achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude.Universidade Federal de São Paulo, Hypertens & Cardiovasc Metab Ctr, Kidney & Hypertens Hosp, Div Nephrol & Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Hypertens & Cardiovasc Metab Ctr, Kidney & Hypertens Hosp, Div Nephrol & Endocrinol, São Paulo, BrazilWeb of Scienc

N-Domain Isoform of Angiotensin I Converting Enzyme as a Marker of Hypertension: Populational Study

The aim of this paper was to investigate the presence of the urinary 90 kDa N-domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n=1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n=795), ACE 90+ (65/90) (n=186), and ACE 90− (65/190) (n=169) based on the presence (+) or absence (−) of the 90 kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90+ compared with the ACE 90− and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90+ group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90− group. There is a high presence of the 90 kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease

6ª Diretriz de monitorização ambulatorial da pressão arterial e 4ª diretriz de monitorização residencial da pressão arterial

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