[Relationship between renal size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure]. / Relación entre el tamaño renal y el perfil de presión arterial en pacientes con poliquistosis renal autosómica dominante sin insuficiencia renal.

BACKGROUND: Enlargement of renal size plays an important role in the development of hypertension in patients with autosomic dominant polycystic kidney disease (ADPKD) and normal renal function. METHODS: A 24h blood pressure monitoring (ABPM) and a renal echography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate > 60 ml/min/1.73 m(2) to study the relationship between renal size and an altered blood pressure profile in prehypertension stages. RESULTS: 13 patients had normal blood pressure, 11 were diagnosed of masked hypertension, 4 had white coat hypertension and 9 had hypertension. We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability. CONCLUSIONS: ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension. This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovascular risk in normotensive patients with ADPKD.

Relación entre el tamaño renal y el perfil de presión arterial en pacientes con poliquistosis renal autosómica dominante sin insuficiencia renal / Relationship between kidney size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure

Antecedentes: El aumento del tamaño renal desempeña un papel importante en el desarrollo de la hipertensión arterial (HTA) en pacientes con poliquistosis renal autosómica dominante (PQRAD) con función renal normal. Material y métodos: Se han practicado a 37 pacientes con PQRAD, filtrado glomerular estimado (FGe) por MDRD>60 ml/min/1,73 m2y supuestamente normotensos, una monitorización de la presión arterial (MAPA) y una ecografía renovesical para investigar la posible relación entre el aumento del tamaño renal y un perfil patológico de presión arterial (PA) en estadios de prehipertensión. Resultados: 13 pacientes resultaron ser normotensos, 11 presentaron HTA enmascarada, cuatro tuvieron HTA de bata blanca y nueve, HTA verdadera. Se ha observado en los pacientes normotensos con patrón reductor de la PA una correlación positiva y estadísticamente significativa entre el tamaño renal y la variabilidad de la presión arterial diastólica (PAD). Conclusiones: La MAPA permite realizar un diagnóstico precoz de la HTA e identificar apacientes con hipertensión enmascarada. Este trabajo sugiere que en pacientes normotensos con PQRAD existe una posible relación entre el tamaño renal y un perfil de PA con mayor riesgo cardiovascular (AU)

Background: Enlargement of renal size plays an important role in the development of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD)and normal renal function. Methods: A 24h blood pressure monitoring (ABPM) and a renal ecography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate >60 ml/min/1,73 m2to study the relationship between renal size and an altered blood pressure profile in prehypertension stages. Results: 13 patients had normal blood pressure, 11 were diagnosed of masked hypertension, 4 had white coat hypertension and 9 had hypertension. We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability. Conclusions: ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension. This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovasular risk in normotensive patients with ADPKD (AU)

Urinary albumin excretion is associated with true resistant hypertension.

Resistant (or refractory) hypertension (RH) is a clinical diagnosis based on blood pressure (BP) office measurements. About one third of subjects with suspected RH have indeed pseudo-resistant hypertension and 24-h ambulatory-blood pressure-monitoring aids to precisely identify them. Our aim was to determine those clinical, laboratory or echocardiographic variables that may be associated with subjects with sustained hypertension (namely true RH). We carried out a cross-sectional analysis of 143 patients consecutively enrolled with the clinical diagnosis of RH. All patients underwent clinical-demographic, laboratory evaluation, 2D-echocardiography and 24-h ambulatory-blood pressure-monitoring. Pseudo-resistant hypertension or white-coat RH was defined if office BP was > or =140 and/or 90 mm Hg and 24-h BP <130/80 mm Hg. One-hundred and three (72%) patients had true RH and 40 (28%) patients had white-coat RH. True RH patients had significantly higher diabetes prevalence and higher office-systolic blood pressure (SBP) levels. Regarding target organ damage, left ventricular mass index (LVMI) and 24-h urinary albumin excretion (UAE) were also higher in true RH after adjustment for possible confounders (P=0.031 and P=0.012, respectively). In a logistic regression analysis, only office-SBP (multivariate OR (95%CI): 1.030 (1.003-1.057), P=0.030) and UAE (multivariate OR (95% CI): 2.376 (1.225-4.608), P=0.010) were independently associated with true RH. We conclude that true resistant hypertension is associated with silent target organ damage, especially UAE. In patients with suspected RH, assessment of 24 h ambulatory BP is the most accurate way to detect a population with high risk for target-organ damage.

Los betabloqueantes a debate: ¿cuál es su papel en el tratamiento actual de la hipertensión arterial? / Beta blockers under debate: what is their role in the current treatment of arterial hypertension?

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[Double blind study of the efficacy and safety of the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg versus the increase of amlopidine dose in essential hypertensive patients not controlled with amlodipine 5 mg]. / Estudio doble ciego de la eficacia y la seguridad de la combinación a dosis fija de 10 mg de enalapril/20 mg de nitrendipino en comparación con el incremento de dosis de amlodipino en pacientes con hipertensión esencial no controlada con 5 mg de amlodipino.

INTRODUCTION: Combined therapy or dose-tiration are acceptable second-line therapeutic options after a first treatment failure. MATERIAL AND METHODS: This double blind clinical trial compared the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg (E/N) with amlopidine 10 mg (A) in 323 hypertensive patients not previously controlled with amlodipine 5 mg. RESULTS: After 6 weeks of treatment, the E/N and A groups had similar percentages of blood pressure normalization (55% versus 60.2%; p = 0.4588). The adverse events related with the treatment were significantly less frequent with E/N than with a (19.8% versus 37%; p = 0.0029), especially due to a lower incidence of malleolar edema in E/N (11.1% versus 33.6%; p < 0.0001). CONCLUSION: Combining the efficacy and tolerability data, treatment with E/N permitted control of blood pressure of 2.8 patients per every patient with adverse events, while this rate for A was 1.6 to 1.

Estudio doble ciego de la eficacia y la seguridad de la combinación a dosis fija de 10 mg de enalapril/20 mg de nitrendipino en comparación con el incremento de dosis de amlodipino en pacientes con hipertensión esencial no controlada con 5 mg de amlodipino / Double blind study of the efficacy and safety of the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg versus the increase of amlopidine dose in essential hypertensive patients not controlled with amlodipine 5 mg

Introducción. En hipertensión arterial el tratamiento combinado y el incremento de la dosis se consideran opciones terapéuticas útiles tras el fracaso del tratamiento inicial. Material y método. Ensayo clínico doble ciego que comparó la combinación a dosis fijas de 10 mg de enalapril/20 mg de nitrendipino (E/N) con 10 mg de amlodipino (A) en 323 pacientes hipertensos no controlados previamente con 5 mg de amlodipino. Resultados. Tras 6 semanas de tratamiento los grupos E/N y A tuvieron porcentajes similares de normalización de la presión arterial (55% frente al 60,2%; p = 0,4588). Los acontecimientos adversos relacionados con el tratamiento fueron significativamente menos frecuentes con E/N que con A (19,8% frente al 37%; p = 0,0029), especialmente por una menor incidencia del edema maleolar en E/N (11,1% frente al 33,6%; p < 0,0001). Conclusión. Combinando los datos de eficacia y tolerancia, el tratamiento con E/N permitió el control de la presión arterial de 2,8 pacientes por cada paciente con acontecimientos adversos, mientras que para A esta tasa fue de 1,6 a 1 (AU)

Introduction. Combined therapy or dosetiration are acceptable second-line therapeutic options after a first treatment failure. Material and methods. This double blind clinical trial compared the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg (E/N) with amlopidine 10 mg (A) in 323 hypertensive patients not previously controlled with amlodipine 5 mg. Results. After 6 weeks of treatment, the E/N and A groups had similar percentages of blood pressure normalization (55% versus 60,2%; p = 0.4588). The adverse events related with the treatment were significantly less frequent with E/N than with a (19.8% versus 37%; p = 0.0029), especially due to a lower incidence of malleolar edema in E/N (11.1% versus 33.6%; p < 0.0001). Conclusion. Combining the efficacy and tolerability data, treatment with E/N permitted control of blood pressure of 2.8 patients per every patient with adverse events, while this rate for A was 1.6 to 1 (AU)

Comparison of the antihypertensive effects of the fixed dose combination enalapril 10 mg/nitrendipine 20 mg vs losartan 50 mg/hydrochlorothiazide 12.5 mg, assessed by 24-h ambulatory blood pressure monitoring, in essential hypertensive patients.

Fixed combinations of calcium channel blockers and angiotensin converting enzyme inhibitors represent an alternative to diuretic-based combination therapy. The aim of the present study was to compare the antihypertensive efficacy of the combination enalapril 10 mg/nitrendipine 20 mg (E/N) vs losartan 50 mg/hydrochlorothiazide 12.5 mg (L/H), assessed by 24-h ambulatory blood pressure monitoring. This multicentre, double-blind, parallel study included 97 hypertensive patients (office diastolic blood pressure (DBP) 90-109 mmHg and daytime DBP > 85 mmHg). After a 2- to 3-week period of single-blind placebo, they were randomized to receive double-blind treatment with E/N (n = 48) or L/H (n = 49) for a 4-week period. The primary outcome measure was the difference in 24-h DBP reduction between treatments from randomization to the end of the double-blind period. Secondary efficacy variables included differences in 24-h systolic (S) BP reduction, daytime, night-time and office SBP and DBP reduction, proportion of responders and controlled patients, trough-to-peak ratio and smoothness indexes. Safety was assessed by the proportion of patients with adverse events and the detection of laboratory abnormalities. No significant differences were observed in the primary outcome measure. The group receiving E/N tended to show greater reductions in most measures (24 h, daytime and office SBP and DBP) and higher BP control rates, but only the difference in the rate of office SBP control (< 140 mmHg) reached statistical significance (42.2 vs 22.4%; P = 0.048). The trough-to-peak ratios and smoothness indexes were similar in both groups. The incidence of adverse events related to the treatment was 27.1% (95% CI 14.5-39.6%) in E/N-treated patients and 14.3% (95% CI 4.5-45.8%) in the L/H group, but differences were not significant. The kind of event more frequently observed were flushing and headache in E/N, and dizziness and asthenia in L/H; all observed adverse events were mild. We conclude that E/N and L/H have a similar antihypertensive efficacy, assessed by office or ambulatory blood pressure monitoring. E/N achieved a significantly higher office SBP control rate, but this was accompanied by an apparently higher proportion of mild adverse events.

Cuestionario de calidad de vida en hipertensión arterial (CHAL) / Quality of life questionnaire for hypertension

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Nitrendipine and enalapril combination therapy in mild to moderate hypertension: assessment of dose-response relationship by a clinical trial of factorial design.

Hypertension is an important cardiovascular risk factor and the goal of its pharmacologic treatment is to reduce morbidity and mortality. Treatment is usually initiated with a low dose of a single agent and titrated to a higher dose as required. As many as 50% of patients require the addition of a second agent to achieve satisfactory blood pressure control. The aim of this study was to assess the dose-response relationship of nitrendipine and enalapril alone or in fixed combination in the treatment of mild to moderate hypertension. A total of 496 patients were enrolled in a multicenter, randomized, double-blind, factorial-design, parallel-group clinical trial comparing placebo, nitrendipine (5, 10, and 20 mg) and enalapril (5, 10, and 20 mg) alone or in combination. After a single-blind, 2-week placebo run-in period, 414 patients whose diastolic blood pressure ranged between 90-109 mm Hg were randomly assigned to a treatment group. The combination of nitrendipine and enalapril, particularly regimens including nitrendipine 20 mg and enalapril 5 or 10 mg, were significantly superior to both monotherapies; mean diastolic blood pressure reductions from baseline to last visit were -12.5 and -14.3 mm Hg, respectively. Response surface analysis provided further evidence that these combinations were optimal in terms of anti-hypertensive efficacy. All treatments were well tolerated and the incidence of adverse events did not differ significantly between groups. In summary, the anti-hypertensive efficacy of the combination was found to be superior to both monotherapies at any doses. The dose combination achieving the greatest blood pressure reduction was nitrendipine 20 mg and enalapril 10 mg.

Relation between clinical and therapeutic variables and quality of life in hypertension.

OBJECTIVE: Study the relation between quality of life (QoL) and various clinical, therapeutic and sociodemographic variables in treated hypertensive patients. MATERIAL AND METHODS: A prospective study was carried out in 92 primary care centres in Spain. A total of 269 hypertensive patients were selected and 106 healthy normotensive individuals were included as controls. At the time of inclusion a wide range of clinical variables was documented. QoL was assessed at baseline and 1 month after the intensification of antihypertensive therapy, using a self-administered, specific hypertension, 56-item questionnaire in addition to the generic EuroQoL-5D. RESULTS: QoL was poorer among the hypertensive subjects than among the normotensive individuals, even adjusting for the differences observed between the groups (age, sex, education and working status). The same was found with the EuroQol-5D. In the hypertensive subjects, after applying a multiple regression equation, only four variables significantly retained their negative impact on QoL: sex (female), greater organ damage and higher heart rate and weight. After the intensification of antihypertensive therapy with irbesartan, QoL improved significantly. Neither the presence of side-effects during the month of follow-up, nor the degree of BP reduction showed a significant impact on QoL, although the latter came close to statistical significance. CONCLUSIONS: Hypertensive patients have significantly poorer QoL than normotensive subjects, even with adjustment for differences. In hypertensives, QoL is affected by some clinical variables that might help us to identify those with worse QoL. Intensification of antihypertensive therapy produced a positive impact on QoL.

Blood pressure variability in Binswanger's disease and isolated lacunar infarction.

UNLABELLED: To determine whether blood pressure (BP) variability is increased in hypertensive patients with Binswanger's disease (BD), we studied two samples of consecutive treated hypertensive patients: (1) 11 with BD (mean age 71.3 +/- 5.2 years); (2) 16 with lacunar infarction (mean age 65.2 +/- 8.3 years) without cognitive impairment. An averaged baseline office BP was obtained for 3 consecutive weeks. Ambulatory BP monitoring was then carried out to obtain the averaged mean systolic (SBP) and diastolic BP, and BP variability was defined as the standard deviation of consecutive BP values. RESULTS: Diurnal SBP variability was significantly increased in the BD group (p = 0.04). However, with the analysis of covariance for age and baseline office BP, the difference was no longer significant (p = 0.17 and p = 0.09, respectively). We conclude that increased BP variability in BD patients is probably due to older age and increased baseline office BP. Increased BP variability may be a risk factor for small-vessel disease, but not for cognitive impairment.

Blood pressure variability and leukoaraiosis amount in cerebral small-vessel disease.

OBJECTIVES: To analyze the correlation between blood pressure (BP) variability and leukoaraiosis (LA) amount in patients with symptomatic cerebral small-vessel disease. MATERIALS AND METHODS: We included 25 hypertensive patients: 13 with Binswanger's disease (BD) and 12 with a first-ever lacunar infarction (LI). Baseline office BP was obtained for 3 consecutive weeks. From a 24-h ambulatory BP monitoring performed 1 week later we obtained average systolic (SBP) and diastolic (DBP) BP for daytime, nighttime and 24-h periods. SBP and DBP variability was defined as the within-subject standard deviation of all readings. A standardized cerebral MR was performed in each patient and an LA score was calculated. RESULTS: No statistically significant correlation was obtained between the LA score and any of the following BP values: 1) Baseline SBP and DBP; 2) 24-h, daytime or nighttime SBP and DBP, and 3) 24-h, daytime or nighttime SBP and DBP variability. CONCLUSION: Increased BP variability is not associated with greater amounts of leukoaraiosis.

Myocardial cell damage in human hypertension.

OBJECTIVES: The goal of this study was to investigate the presence of myocardial cell damage in patients with systemic hypertension and its relationship with left ventricular hypertrophy (LVH). BACKGROUND: Although initially compensatory, LVH adversely affects myocellular integrity and contributes to congestive heart failure in hypertensive patients. Noninvasive detection of myocardial damage can be of value. METHODS: We performed imaging studies with 111In-labeled monoclonal antimyosin antibodies to identify myocardial damage in 39 patients with systemic hypertension and variable degrees of LVH. Three groups were considered: 16 asymptomatic patients with normal echocardiographic left ventricular mass (LVM) (group I); 14 asymptomatic patients with LVH (group II) and 9 patients with symptomatic hypertensive heart disease and advanced LVH (group III). The severity of myocardial damage was represented as heart-to-lung (target-to-background) antibody uptake ratio (normal: <1.55). RESULTS: Mean LVM index was 105+/-14 g/m2 in group I, 124+/-24 in group II and 174+/-29 in group III. Heart-to-lung ratios of antimyosin uptake were: 1.45+/-0.14 in group I, 4 of the 16 (25%) patients showing an abnormal scan; 1.50+/-0.07 in group II with abnormal scans in 2 of the 14 (16%) patients and 1.77+/-0.16 (p < 0.001) in group III, all 9 patients presenting with abnormal antimyosin scans. On multivariate regression analysis LVM index was the main variable that independently correlated with the degree of myocardial uptake of antimyosin (r = 0.815; p = 0.001). CONCLUSIONS: This study provides the first in vivo evidence of myocyte damage in patients with hypertension. The severity of myocardial damage can be related to the magnitude of LVH.

Usefulness of the I/D angiotensin-converting enzyme genotype for detecting the risk of left ventricular hypertrophy in pharmacologically treated hypertensive men.

The insertion/deletion polymorphism (I/D) of the angiotensin-converting enzyme (ACE) gene has been associated in some studies with a higher prevalence of left ventricular hypertrophy (LVH), but few of them were performed on pharmacologically treated hypertensive patients. The present study was undertaken to determine whether ACE genotype determination could help in the identification of pharmacologically treated hypertensive patients at a higher risk of LVH. Ninety-six consecutive men with essential hypertension were selected for the study. Left ventricular mass (LVM) was assessed by echocardiography and indexed by body surface area and 82 patients were considered suitable for the study. Three groups of patients were defined on the basis of their I/D ACE genotype: DD (n = 39), ID (n = 33) and II (n = 10). There were no statistically significant differences between the three groups regarding to the severity of hypertension at diagnosis, degree of control of blood pressure or type of antihypertensive drug therapy used. No statistically significant differences were found between the three groups regarding to LVM index (total 124 +/- 31, DD 121 +/- 29, ID 127 +/- 35 and II 122 +/- 18 g/m2), relative wall thickness (total 0.5 +/- 0. 2, DD 0.5 +/- 0.3, ID 0.48 +/- 0.07 and II 0.47 +/- 0.04) or prevalence of LVH (total 34%, DD 31%, ID 39% and II 30% by Cornell criteria and total 39%, DD 33%, ID 45% and II 40% by Framingham criteria). Furthermore, the I and D allele frequency distribution was similar in the whole group of patients, in patients with LVH, and in a control group of healthy volunteers. Our data do not support that the I/D ACE genotype determination helps in identifying treated hypertensive patients at higher risk of LVH. Journal of Human Hypertension (2000) 14, 327-331

A randomized, double-blind comparison of the antihypertensive efficacy and safety of once-daily losartan compared to twice-daily captopril in mild to moderate essential hypertension.

INTRODUCTION: The antihypertensive efficacy and safety of losartan, a specific and selective angiotensin II (AII) receptor antagonist, was compared to captopril in patients with mild or moderate essential hypertension. DESIGN: This multinational, randomized trial consisted of a 4-week single-blind, placebo baseline period followed by a 12-week double-blind, parallel comparison of once-daily administration of losartan 50 mg or twice-daily administration of captopril 25 mg. After 6 weeks of treatment, the daily dosage was doubled in patients whose sitting diastolic blood pressure (SiDBP) remained > or = 90 mm Hg. PATIENTS: Patients with essential hypertension having a mean trough SiDBP of 95-115 mm Hg after the placebo baseline period were randomized to losartan (N = 192) or captopril (N = 204) treatment. MAIN OUTCOME MEASURES: The primary efficacy variable was the mean change from baseline to Week 12 in trough SiDBP. Safety was assessed by recording spontaneously reported or observed adverse experiences and clinical laboratory measurements. RESULTS: After 12 weeks, both treatments produced clinically important reductions in trough SiDBP and sitting systolic blood pressure (SiSBP). These mean reductions (SiDBP, SiSBP) were significantly greater in the losartan group (-11.5 and -15.4 mm Hg, respectively) than in the captopril group (-9.3 and -12.2 mm Hg, respectively) (p = 0.010 for diastolic and p = 0.023 for systolic). The percentage of patients exhibiting an excellent (trough SiDBP < 90 mm Hg) or good (trough SiDBP > 90 mm Hg, with decrease of > or = 10 mm Hg) antihypertensive response to losartan and captopril therapy at Week 12 was comparable (60.0% and 54.7%, respectively). The percentage of patients reporting a clinical adverse experience considered drug-related by the investigator was 13% in the captopril group and 10% in the losartan group. The incidence of drug-related cough was 2.6% in the losartan group and 4.4% in the captopril group. CONCLUSION: Once daily administration of losartan 50 to 100 mg is an effective treatment for patients with essential mild to moderate hypertension. The antihypertensive efficacy of losartan 50/100 mg is significantly greater than that of twice daily captopril 25/50 mg. Both treatments were generally well-tolerated. The number of patients with the side effect of cough was higher following captopril.