Relationship between microalbuminuria and cardiac structural changes in mild hypertensive patients

The aim of this study was to determine the relationship between urinary albumin excretion (UAE), cardiac structural changes upon echocardiography and 24-h ambulatory blood pressure (ABPM) levels. Twenty mild hypertensive patients (mean age 56.8 ± 9.6 years) were evaluated. After 2 weeks of a washout period of all antihypertensive drugs, all patients underwent an echocardiographic evaluation, a 24-h ABPM and an overnight urine collection. Systolic and diastolic blood pressure during 24-h ABPM was 145 ± 14/91 ± 10 mmHg (daytime) and 130 ± 14/76 ± 8 mmHg (nighttime), respectively. Seven (35 percent) patients presented UAE > or = 15 æg/min, and for the whole group, the geometric mean value for UAE was 10.2 x/÷ 3.86 æg/min. Cardiac measurements showed mean values of interventricular septum thickness (IVS) of 11 ± 2.3 mm, left ventricular posterior wall thickness (PWT) of 10 ± 2.0 mm, left ventricular mass (LVM) of 165 ± 52 g, and left ventricular mass index (LVMI) of 99 ± 31 g/m². A forward stepwise regression model indicated that blood pressure levels did not influence UAE. Significant correlations were observed between UAE and cardiac structural parameters such as IVS (r = 0.71, P<0.001), PWT (r = 0.64, P<0.005), LVM (r = 0.65, P<0.005) and LVMI (r = 0.57, P<0.01). Compared with normoalbuminuric patients, those who had microalbuminuria presented higher values of all cardiac parameters measured. The predictive positive and negative values of UAE > or = 15 æg/min for the presence of geometric cardiac abnormalities were 75 and 91.6 percent. These data indicate that microalbuminuria in essential hypertension represents an early marker of cardiac structural damage

Intima-media thickness evaluation by B-mode ultrasound: Correlation with blood pressure levels and cardiac structures

The aim of this study was to analyze the thickness of the intima-media complex (IMC) using a noninvasive method. The carotid and femoral common arteries were evaluated by noninvasive B-mode ultrasound in 63 normotensive and in 52 hypertensive subjects and the thickness of the IMC was tested for correlation with blood pressure, cardiac structures and several clinical and biological parameters. The IMC was thicker in hypertensive than in normotensive subjects (0.67 ± 0.13 and 0.62 ± 0.16 vs 0.54 ± 0.09 and 0.52 ± 0.11 mm, respectively, P<0.0001). In normotensive patients, the simple linear regression showed significant correlations between IMC and age, body mass index and 24-h systolic blood pressure for both the carotid and femoral arteries. In hypertensives the carotid IMC was correlated with age and 24-h systolic blood pressure while femoral IMC was correlated only with 24-h diastolic blood pressure. Forward stepwise regression showed that age, body mass index and 24-h systolic blood pressure influenced the carotid IMC relationship (r2 = 0.39) in normotensives. On the other hand, the femoral IMC relationship was influenced by 24-h systolic blood pressure and age (r2 = 0.40). In hypertensives, age and 24-h systolic blood pressure were the most important determinants of carotid IMC (r2 = 0.37), while femoral IMC was influenced only by 24-h diastolic blood pressure (r2 = 0.10). There was an association between carotid IMC and echocardiographic findings in normotensives, while in hypertensives only the left posterior wall and interventricular septum were associated with femoral IMC. We conclude that age and blood pressure influence the intima-media thickness, while echocardiographic changes are associated with the IMC

Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring.

OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significantly reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trando-lapril during treatment of mild-to-moderate essential systemic hypertension.

[Comparative effects of captopril and chlorthalidone on glucose tolerance and insulin levels essential hypertensives]. / Comparação entre os efeitos de captopril e da clortalidona sobre a tolerância à glicose e os níveis sérícos de insulina em hipertensos essenciais.

PURPOSE: To compare the effects of chlortalidone (CL) and captopril (Cp) upon glucose tolerance and serum insulin levels in essential hypertensive patients. METHODS: Non obese essential hypertensive patients with normal glucose tolerance test (OGTT) and diastolic blood pressure (DBP) > 90 mmHg and < or = 115 mmHg in the seated position were treated, in a randomized fashion, with Cp or CL during 16 weeks, after 16 weeks of placebo. The OGTT was performed after placebo and after active therapy, with serum insulin levels determinations carried out before and 120 minutes after oral glucose load. RESULTS: Twenty four patients in the CL group and 19 in the Cp concluded the study. Hypocalemia (serum potassium < 3.8mEq/L or serum potassium reductions > or = 0.9mEq/ L) occurred in nine patients of the CL group (CL H). In this group CL therapy induced increments in the area under the curve of glycemia during OGTT (582 vs 610mg/h/dL, p < 0.05) that were not observed in the normocalemic patients of the CL (CLN) or Cp groups. Serum insulin levels during OGTT did not change with active therapy in all three groups. The insulin sensitivity index, however, decreased significantly in the CLH (1.9 vs 1.4; p < 0.05) and CLN (10.1 vs 4.3, p < 0.05) but remained unchanged in the Cp group (3.1 vs 2.5; NS). The insulin response to glucose index increased in the Cp (0.28 vs 0.40; p < 0.05) group but not in the CLH (0.25 vs 0.42; NS) and CLN (0.07 vs 0.24). CONCLUSION: The antihypertensive therapy with chlortalidone in essential hypertensive patients may result in reductions in the peripheral sensitivity to insulin that can be accompanied by increases in glycemic levels after oral glucose load, particularly in patients who develop hypocalemia. Our results indicate that Cp therapy induces increments in insulin response to glucose without detectable changes in peripheral insulin sensitivity.

[Glucose tolerance test and insulin secretion in patients with essential hypertension. Effect of enalapril]. / Tolerância à glicose e secreção de insulina em pacientes com hipertensão arterial essencial. Efeito do enalapril.

PURPOSE: To investigate the effects of enalapril upon glucose and insulin metabolism in patients with essential hypertension. METHODS: After 4 weeks of washout and 2 weeks of placebo therapy, 10 hypertensive patients were treated with enalapril for 12-14 weeks. Intravenous glucose tolerance test (IVGTT) during 182 minutes was performed before and after treatment. Venous blood samples were drawn for glucose and insulin determinations. RESULTS: Enalapril caused a significant fall on systolic (-19 +/- 3 mmHg) and diastolic (-10 +/- 2 mmHg) blood pressure. During IVGTT, enalapril induced a small decrease in the area under the curve of glucose (placebo 18,966 +/- 732.6 mg/dl.min and enalapril 17,575 +/- 916.1 mg/dl.min) associated with a small increase in the area under the curve of insulin (placebo 3,155 +/- 446.99 mU/ml.min and enalapril 3.577 +/- 393.92 mU/ml.min). A small rise in the disappearance rate of glucose (Kg) was also observed following enalapril (placebo 2.09 +/- 0.33 and enalapril 2.56 +/- 0.53). The insulin responsiveness to glucose increased significantly from 0.16 +/- 0.020 during placebo to 0.21 +/- 0.023 during enalapril. The insulin sensitivity remained unchanged (placebo 1.97 +/- 0.24 and enalapril 1.83 +/- 0.21). CONCLUSION: In hypertensive patients, the treatment with enalapril induced a small increase (not significant) in glucose tolerance caused by a significant rise in insulin responsiveness to glucose since no modification in insulin sensitivity was observed.

[Fosinopril in a daily single dose in mild and moderate hypertension. Brazilian multicenter study]. / Fosinopril em dose única diária na hipertensão leve e moderada. Estudo multicêntrico brasileiro.

PURPOSE: To evaluate during 12 weeks the effectiveness and safety of once-a-day fosinopril (10 or 20 mg/day comparative to placebo) in mild to moderate hypertensives according to an open design comparative to placebo. METHODS: One hundred and nineteen patients were studied; 52 +/- 11 years (mean +/- sd) range 18 a 76 years, 86 women and 33 men, 57% whites, 26% blacks and 17% mulattos, 71 mild hypertensives (95 < or = diastolic pressure < or = 104mmHg) e 48 moderate hypertensives (101 < diastolic pressure < or = 115mmHg). RESULTS: There was a significant reduction in systolic/diastolic pressure on the 6th week of treatment (from 161 +/- 16/103 +/- 7 before to 148 +/- 16/94 +/- 9mmHg on the 6th week). On the 12th week of treatment there was an additional significant reduction in systolic/diastolic pressure (from 148 +/- 16/94 +/- 9 on the 6th week to 145 +/- 17/89 +/- 8mmHg on the 12th week). There was a "favorable" response in 71% of the patients on the 12th week; 62% showed diastolic pressure < or = 90mmHg and 9% presented diastolic reduction > or = 10mmHg. There was no difference in the normalization rates between whites and non-whites, mild and moderate hypertensive, obese and non-obese patients, under or above 50 years of age and those patients from no drug-treatment to those on 3 drug before the study. There was no clinically relevant changes in laboratory evaluations before and at the end of the study. The number of adverse reactions was reduced in comparison with previous treatment. CONCLUSION: Fosinopril, according to our and others data, is effective and safe for the treatment of mild to moderate hypertensives, in whites or non-whites, obese or non-obese, younger or older than 50 years and receiving 0 or 3 drugs before the study.

[Captopril in mild and moderate hypertension resistant to diuretics: predictive value of the efficacy by captopril acute test]. / Captopril na hipertensão arterial leve e moderada resistente a diurético: valor preditivo da eficácia através do teste agudo do captopril.

PURPOSE: To evaluate if acute blood pressure response with captopril can be applied as a predictive test of treatment efficacy in hypertensive patients uncontrolled with large dose of diuretics. METHODS: Mild and moderate 120 uncontrolled hypertensive patients treated with hydrochlorothiazide 100 mg, were submitted to captopril (25 mg) test. The systolic (SBP) and diastolic (DBP) blood pressure acute and chronic responses were correlated and the linear discriminate function (LDF) and qui-square were applied to test the treatment efficacy. Previously two groups (G) patients were obtained as bad responders (G1) and good responders (G2) respectively, if the mean arterial pressure fall less or equal/more than 15% at the end of the associated treatment with diuretic and captopril. RESULTS: Mean arterial pressure values during placebo were 168 +/- 2/109 +/- 1 mmHg. This values after diuretic and associated captopril treatment were, respectively, 151 +/- 1/101 +/- 1 and 137 +/- 1/90 +/- 1 mmHg, all significant different (p < 0.05). Blood pressure normalization was obtained in 58% of patients. The calculated LDF formula were: LDF = 7.92 - % SBP +/- 1.21 delta % DBP. The G1 LDF mean value was 192 and 361 to G2. The value 276 represents the separation medium point between both groups. As far the distance from the separation medium point for a calculated LDF for a calculated LDF for a problematic patient, as more will be the probability for this patient to belong to this group. LDF and qui-square classified correctly, respectively, 80% and 47% of patients in G1. To G2 good responders patients, LDF and qui-square agreed, respectively, in 72 and 77%. CONCLUSION: The results obtained suggest that captopril test, could be useful as an auxiliary methodology to select hypertensive patients, uncontrolled with diuretic treatment, which might benefit with the association of converting enzyme inhibitors drugs.

[Captopril in mild and moderate arterial hypertension resistant to diuretic therapy. A multicenter study]. / Captopril na hipertensão arterial level e moderada resistente à diureticoterapia. Estudo multicêntrico.

PURPOSE: To evaluate the antihypertensive effect of captopril in mild and moderate hypertensive patients uncontrolled with diuretics. METHODS: Low dose of captopril (25 to 50 mg) bid were associated during 9 weeks in 120 patients previously treated with 100 mg of hydrochlorothiazide. A subgroup of patients (74) were followed additionally for 3 weeks with the same dose of the drugs administered as a single dose. The patients were clinically evaluated after two weeks placebo, and each three weeks of active drugs. Blood pressure normalization were considered when diastolic arterial pressure was < or = 90 mmHg. Laboratory tests were measured before diuretic, before captopril and at the end of combined twelve weeks treatment. RESULTS: After 15 days washout, the baseline supine arterial pressure, 168 +/- 2/ 109 +/- 1 mmHg decrease significantly with diuretic to 151 +/- 1/ 101 +/- 1 mmHg and the drop was further increased with captopril b.i.d., with a mean dose of 44 +/- 1 mg, to 137 +/- 1/ 90 +/- 1 mmHg. Blood pressure normalization was obtained in 58% patients with captopril b.i.d. and in 63% as single dose. Blood pressure normalization was achieved in 63% of non-white patients and in 56% patients over 45 years old. Plasmatic potassium decreased significantly with diuretic and did not recovered when captopril was associated. CONCLUSION: Our results indicate that the addition of low dose of captopril twice or once a day may result in a marked additional blood pressure reduction in cases of insufficient control by the diuretic alone.

Tratamento da hipertensäo arterial sistêmica com urapidil: estudo multicêntrico comparativo com nifedipina / Treatment of sistematic arterial hypertension with urapradil multicenter studies comparative with nifedipina

Estudo multicêntrico, aberto, comparativo entre o Urapidil e a Nifedipina, alocando os pacientes, aleatoriamente, em dois grupos de tratamento, com 95 pacientes (46 pacientes tratados com Urapidil e 49 pacientes tratados com Nifedipina). Houve um período de washout de duas a quatro semanas e, um período de tratamento ativo de 10 semanas, sendo que, após duas semanas, a dose inicial (Urapidil: 60mg/d e Nifedipina: 40mg/d) foi duplicada nos pacientes näo-responsivos. O critério de normalizaçäo foi o de uma pressäo diastólica igual ou inferior a 90 mmHg ou 10% na reduçäo, se a diastólica fosse inferior a 100mmHg. Nos 95 pacientes estudados a porporçäo de pacientes responsivos foi de 78% paa o Urapidil e de 76% para a Nifedipina; a queda de pressäo levou a 139/88mmHg; no grupo do Urapidil e 131/83mmHg no grupo da Nifedipina. A tolerância foi satisfatória com o Urapidil, sendo as principais queixas a vertigem, o mal-estar e a fraqueza que apareceram em 10 doentes; entre os pacientes tratados com Nifedipina 17 apresentaram queixas de cefaléia e 14 pacientes apresentaram vertigem e flushing

Stress and hypertension: studies in three experimental models

The effects of three models of stress upon blood pressure and central responsiveness to angiotensin II (AII) and noradrenaline (NA) were assessed in rats. Considering general parameters of stress efficacy, all models were effective to induce stress but hypertension only occurred in animals submitted to rapid eye movement sleep deprivation (REM-sd) and electric shock (ES). An increased central pressor effect of AII and NA was observed in these groups. On the other hand, restriction (R) did not increase blood pressure or central responsiveness to AII or NA. Instead of hypertension, R induced gastric ulcers and testis atrophy. Thus, hypertension occurs only in some models of stress and may be due to increased central responsiveness to AII and NA.

Hypertension. A major public health problem in Brazil.

Data collected from various geographical areas show that hypertension is a major public health problem in Brazil. Hypertension is estimated to occur in over 8 million Brazilians and cardiovascular disease-related mortality figures, to which hypertension is a major contributor, increased from 11.8% of the total mortality rate in 1930 to 30.8% in 1980. Costs involved in the treatment of hypertensive patients are very high since hypertension was among the 3 most frequent clinical diagnoses in outpatient visits in 1985. Hypertension is also a major cause of temporary or permanent work incapacitation among Brazilians and data from São Paulo show that hypertension is very common among workers. Finally, demographic tendencies in São Paulo indicate that older age groups have increased in the general population during the past 2 decades. These data, when taken altogether, indicate that hypertension is a major public health problem in Brazil.

Hypertension and diabetes. Clinical problems.

The choice of an appropriate antihypertensive agent and the hazards of postural hypotension are common problems faced in the treatment of diabetic hypertensive patients. The results of 3 studies addressing these problems are described in this report. In the first study, indoramin, an alpha-blocking agent, was administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension. Blood pressure control was achieved in 57% of patients with mild, and in none with moderate hypertension. The blood glucose and insulin responses to an oral 50g glucose loading, as well as the blood concentrations of HbA1 did not change during therapy. Seven patients were excluded because of side effects. In 4 of them postural hypotension was observed. In the second study, the effects of angiotensin-converting enzyme (ACE) inhibitors, administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension, were evaluated. Blood pressure control was achieved in 78% of the patients on captopril (n = 14) and in 74% of patients on enalapril therapy (n = 23). Symptomatic postural hypotension (n = 2) and hyperkalaemia (n = 2) were observed with both drugs. Significant reductions in 24-hour urinary protein or albumin excretion were detected in 12 patients on enalapril therapy. No changes in 2-hour postprandial blood glucose and HbA1 levels were observed during therapy with ACE inhibitors. In the third study, dopaminergic antagonist agents were evaluated in diabetic patients with orthostatic hypotension. In 7 patients metoclopramide (20mg intravenously) reduced the fall in mean arterial pressure induced by upright tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

Tratamento da crise hipertensiva com captopril. / Treatment of hypertensive crisis with captopril

Avaliou-se a eficiencia do captopril, um inibidor da enzima conversora, no tratamento de 28 pacientes em crise hipertensiva de variadas etiologias: 12 com hipertensao arterial maligna, 6 com hipertensao acelerada, 4 com hipertensao renovascular e 6 com hipertensao renovascular arterial refrataria. A resposta imediata ao captopril foi mais intensa nos pacientes portadores de hipertensao arterial acelerada e maligna e hipertensao renovascular. Assim, em 14 dos 18 pacientes com hipertensao acelerada e maligna, doses entre 150 e 300 mg de captopril foram suficientes para reduzir a pressao arterial a niveis proximos da normalidade. Nos outros 4 pacientes deste grupo, necessitou-se de um diuretico para controlar a pressao arterial. Os 4 pacientes com hipertensao renovascular apresentaram reducoes similares na pressao arterial, porem com doses menores de captopril. Os 6 pacientes portadores de hipertensao arterial refrataria apresentaram menores reducoes pressoricas com doses de captopril entre 50 e 150 mg.Concluiu-se que captopril foi eficaz para o tratamento inicial de crises hipertensivas de diversas etiologias