Efficacy of benazepril monotherapy in moderate essential hypertension studied by automatic ambulatory blood pressure monitoring

Authors examined the effects of benazepril, regarding the length of effectiveness by ambulatory blood pressure monitoring (ABPM), drug tolerable, and the compliance of patients in mild to moderate essential hypertension. 14 patients were treated with benazepril monotherapy. Six of them were newly diagnosed, and the rest had already been treated for hypertension. At the start, after six and 12 weeks, 24-hour monitoring was performed. Casual blood pressure (BP) measurements and detection of side-effects were also performed at 3rd and 9th-week. Prior the study the average daytime BP measured by ABPM was 149.1 +/- 7.7/96.6 +/- 4.7 mmHg. 10 mg of benazepril was first administered in the morning. By the end of the sixth week the average BP was significantly decreased (daily average: 139.1 +/- 9.9/88.2 +/- 7.6 mmHg). The daytime diastolic average BP of 8 patients was lower than 90 mmHg and the other's daily dose was raised to 20 mg. During the 12th-week we found optimal tension in 11 patients, while in two others there was also a significant decrease. The daily average BP was 134.7 +/- 7.5/85.6 +/- 6.6 mmHg. In comparison the data at the beginning of the study here was significant decrease in the 24-hour, daytime and night-time BP, in the hypertension time-index and the hyperbaric impact, both in systolic and diastolic levels. During the 12th-week period the diurnal index was unchanged. The early morning BP decreased by the end of the 3rd month from 148.6 +/- 14.1/98.5 +/- 11.7 mmHg to 135.2 +/- 13.5/93.4 +/- 11.2 mmHg. Sustained side-effect did not occur. The patient's compliance to benazepril was excellent. Authors conclude that benazepril monotherapy lowered in 92.8%, and normalized in 78.5% the blood pressure of patients suffering from mild to moderate essential hypertension. The unchanged diurnal index, and the decrease in the early morning blood pressure suggest the 24-hour effect of benazepril.     

Epidemiology of extrapulmonary tuberculosis among persons with AIDS in the United States

We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3 +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs. 132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.     

Short report: ramipril and hydrochlorothiazide combination therapy in hypertension: a clinical trial of factorial design. The East Germany Collaborative Trial Group

OBJECTIVE: To identify appropriate dosages of ramipril and hydrochlorothiazide (HCT) when given in combination once a day for the treatment of essential hypertension. DESIGN: A 2- or 4-week placebo run-in followed by 6-week, double-blind, parallel-group phase: 4 x 3 factorial (2.5, 5 and 10 mg ramipril; 12.5 and 25 mg HCT; all six combinations; placebo). SETTING: Office practice (21 centres). PATIENTS AND PARTICIPANTS: Patients with mild-to-moderate essential hypertension (World Health Organization stage I-II; supine diastolic blood pressure 100-115 mmHg in last 2 weeks of run-in): 581 enrolled, 534 randomly assigned to double-blind therapy and 517 completed. MAIN OUTCOME MEASURES: Reduction in supine and standing blood pressure. RESULTS: In pairwise comparisons, the combinations of 5 mg ramipril with 12.5 and 25 mg HCT and 10 mg ramipril with 12.5 mg HCT consistently produced significantly greater blood pressure reductions than their respective components. Response surface analyses were performed, and a stairstep model was constructed to characterize the shape of the dose-response surface. The combinations involving 5 and 10 mg ramipril with 12.5 and 25 mg HCT were again more effective than their components. Withdrawals and adverse effects were minimal for all treatments. A large drop in serum potassium was observed on 25 mg HCT, but not on combination therapy. Addition of ramipril appeared to reduce the hyperuricaemic effect of HCT. CONCLUSIONS: Several dosage combinations of ramipril plus HCT produced significantly greater blood pressure reductions than the monotherapies at the same dosages. Overall, the combination of 5 mg ramipril and 25 mg HCT gave the best mean reduction. Combination therapy with ramipril plus HCT was safe and effective for patients with mild-to-moderate essential hypertension.     

Change of circadian pattern of arterial pressure in patients with congestive heart failure treated with perindopril, an inhibitor of angiotensin-converting enzyme (ACE)

The 24-h profile of blood pressure (BP) was studied in 28 patients (21 males and 7 females) with congenital heart failure (CHF) of NYHA class II-III (ejection fraction < 45%). The patients were 46 to 76 years of age and had postinfarction cardiosclerosis. They had not received ACE inhibitors before. Two groups were formed basing on the presence of hypertension. Perindopril was administered in a single daily dose of 2 mg or higher if demanded to reduce symptoms of CHF and/or to normalize BP. The treatment continued for 3 months. The 24-h BP profile was assessed using portable device SpaceLabs 90207 (USA). In CHF patients with hypertension perindopril significantly lowered mean 24-h, day and night BP and its loads, reestablished two-phase circadian rhythm of AP and corrected BP variability. In CHF patients free of hypertension significant changes of the profile were not registered. It is evident that unwanted changes in the BP 24-h profile due to perindopril were absent in CHF normotensives.     

Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life

OBJECTIVE: To establish the efficacy of 24-h ambulatory and casual blood pressure (BP) reduction, and the tolerability of once daily felodipine extended release (ER) 2.5 mg and felodipine ER 5 mg as monotherapy. DESIGN: Randomised, double-blind placebo controlled 6 weeks parallel study. SETTING: From 15 general practices centres (with 19 GPs) in the region of the University of Maastricht, The Netherlands. SUBJECTS: A total of 129 subjects aged 50-80 years with primary hypertension were screened; 27 men and 61 women with a casual diastolic BP of 100-115 mm Hg and/or a systolic BP of less than 200 mm Hg entered the study. MAIN OUTCOME MEASURES: Casual and 24-h ambulatory BP and a subjective symptom assessment (SSA) questionnaire after 6 weeks of therapy. RESULTS: After correlation for placebo response the mean casual systolic/diastolic BP (SBP/DBP) reduction was 10/5 mm Hg (NS) and 12/10 mm Hg (P < 0.05) for felodipine ER 2.5 and 5 mg, respectively. By using 24-h ambulatory BP measurements these reduction were 6/4 mm Hg (NS) and 13/8 mm Hg (P < 0.05), respectively. No significant difference for SBP and DBP was found during the night time between felodipine 2.5 and placebo (-1/0). Felodipine ER 5 mg lowered the BP load significantly during both daytime and night time but felodipine ER 2.5 mg only for DBP during the daytime. There was a significant difference for the number of responders between placebo (28%) vs felodipine ER 2.5 mg (55%) and ER 5.0 mg (59%). Both felodipine dosages and placebo were comparable in (a low) number of adverse events and results of the SSA. CONCLUSIONS: During daytime felodipine ER 2.5 mg and 5 mg are effective in BP lowering in elderly hypertensive patients. However, only felodipine ER mg is effective in reducing BP during night time (22.00-7.00). Only felodipine ER 5 mg has a significant reducing effect on BP load during day and night time. Both felodipine ER 2.5 and ER 5.0 have a significant effect on the responder rate. It appeared from this study that compared to placebo, and in contrast with felodipine ER 5 mg, the ER form of felodipine 2.5 mg has no BP lowering effect during night time in elderly patients. To assess the effectivity during night time of felodipine ER 2.5 mg in an individual patient it is recommendable to measure the BP at the end of the dose interval.     

Changes in blood pressure 24 hour monitoring data and quality of life in patients with systolic hypertension treated with arifon

AIM: The study of quality of life and 24-h monitoring blood pressure data in elderly patients with isolated systolic hypertension (SH) on arifon monotherapy. MATERIALS AND METHODS: 22 patients over 65 (mean age 69.8 +/- 1.3 years) suffering from SH entered the open trial. 24-h monitoring of blood pressure was performed at least 2 weeks after discontinuation of the previous antihypertensive treatment and after 4 weeks of arifon monotherapy (2.5 mg once a day). Quality of life was evaluated according to the standard SIP questionnaire. RESULTS: Arifon 4-week treatment resulted in a significant fall of systolic pressure for 24 hours, day and night (by 16.2, 13.7 and 17.4%, respectively; p < 0.001). Variability of blood pressure did not change much. 24-h index for systolic and diastolic blood pressure increased 2-fold and by 46%, respectively. Moreover, the rate of the systolic pressure growth in the morning hours decreased by 36.7% (p < 0.05). Psychosomatic status by SIP questionnaire changed for the best. CONCLUSION: Arifon is an effective treatment of SH and improves quality of life.     

Accidental occupational exposure of intravenous nurses to human immunodeficiency virus. Anticipating the consequences

The relationship of parental history of high blood pressure (HBP) to blood pressure (BP) was estimated in three Japanese population samples, totalling 591 men and women aged 20-59 years, from the INTERSALT study. Parental history of HBP was defined as reported HBP by their father and/or mother. With adjustment for antihypertensive medication, body mass index, alcohol intake, and Na/K ratio in 24-h urine, for participants with a parental history of HBP compared to those without a history, BP was higher for three to four age-sex strata, both for systolic and diastolic pressure (SBP, DBP), by 3.3 to 6.8 and 2.7 to 5.5 mm Hg respectively, with four of these six positive associations statistically significant. This finding was stronger for persons aged 40-59 than for those aged 20-39. These data support the judgment that for persons with a parental history of HBP, BP is apt to increase more with age due to combined effects of genetic and environmental factors. Such people especially need to control their lifestyles carefully, including to maintain an optimal intake of salt (eg, <70 mmol/day) and a high potassium intake, to avoid high alcohol consumption, and keep weight moderate, for the prevention of hypertension.     

Double-blind, parallel, comparative multicentre study of a new combination of diltiazem and hydrochlorothiazide with individual components in patients with mild or moderate hypertension

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a new combination preparation of diltiazem (150 mg) and hydrochlorothiazide (12.5 mg) with the individual constituents in patients with mild/moderate hypertension. DESIGN: Multi-centre, double-blind, randomised parallel group study. PATIENTS: Seventy-one patients with essential hypertension were recruited to the study. TREATMENT: Following completion of the placebo run-in period 63 patients fulfilled the prerandomisation criteria and entered the 10 week treatment period. Patients were randomised to receive either the combination preparation (D 150 mg/H 12.5 mg), diltiazem (150 mg) or hydrochlorthiazide (12.5 mg). The dosage was increased in three patients who had not attained target blood pressure (BP) control after 6 weeks. OUTCOME MEASURES: Response to treatment assessed by change from baseline in clinic and 24 h ambulatory BP. RESULTS: The proportion of patients achieving target BP (a reduction in resting supine diastolic blood pressure (DBP) to below 90 mm Hg or a reduction of 10 mm Hg from baseline) was 80% in the combination group, 55% in the diltiazem group, and 38% in the hydrochlorothiazide group. The respective figures for reduction in supine DBP from baseline were 13.5 mm Hg, 11.2 mm Hg and 5.9 mm Hg. A similar treatment order appeared throughout each of the efficacy variables. BP control throughout the 24 h dosing interval was demonstrated by ambulatory BP monitoring. Each treatment was well tolerated. CONCLUSION: This study provides clear evidence of the efficacy of combination therapy with diltiazem and hydrochlorothiazide in the management of patients with hypertension.     

Histochemical detection of lymphatic drainage pathways in the middle nasal meatus

AIM: Assessment of the antihypertensive effect of doxazosin, alpha-1 blocker, as well as its action on lipid and carbohydrate metabolism, microcirculation and platelet function in patients with non-insulin-dependent diabetes mellitus (NIDDM). MATERIALS AND METHODS: Doxazosin (tonocardin) treatment was given for 11 weeks to 33 NIDDM patients with concomitant hypertension. The clinical examination comprised evaluation of central hemodynamics, vessels of the fundus of eye, lipid and carbohydrate metabolism, renal function, platelet aggregation. RESULTS: Tonocardin produced a fall in the systolic blood pressure (BP) by 14%, in the diastolic BP--by 17%. The 24-h profile of BP, lipid and purine metabolism, microcirculation of the vessels of the fundus of eye also improved. Total peripheral vascular resistance, left ventricular myocardial mass and platelet aggregation. Carbohydrate metabolism remained unchanged. CONCLUSION: Monotherapy with tonocardin (2-8 mg/day) is effective and safe in the treatment of arterial hypertension in NIDDM patients.     

Long-term therapy of bronchial asthma with ingacort

To study the effectiveness of ACE-inhibitors in diabetic nephropathy (DN) 12 male and 16 female patients aged 13-21 years with DN having normal blood pressure (BP) were given ramipril (tritace) in a dose 2.5-5 mg/day in the course of 12-24 weeks. Efficacy and safety of the treatment were assessed by changes in albuminuria and proteinuria, BP. Reduction of albuminuria occurred in 19(79.1%) out of 24 patients with microalbuminuria, in 13(54.1%) of them urine excretion of albumin returned to normal levels. All the patients with proteinuria and macroalbuminuria benefited from ramipril therapy because their proteinuria diminished or even disappeared (2 cases). The persistence of the antiproteinuria effect on posttreatment week 12 was 66.6%. Ramipril effect on BP was minimal. It is inferred that ramipril is effective in the treatment of DN at the stage of microalbuminuria and proteinuria in patients with normal BP.     

Left ventricular hypertrophy and ambulatory blood pressure monitoring in chronic renal failure

BACKGROUND: Left ventricular hypertrophy (LVH) is both common and an important predictor of risk of death in end-stage renal failure (ESRF). In mild to moderate chronic renal failure (CRF), the timing of onset of LVH and the factors involved in its initial development have not been fully elucidated. The present study was undertaken to examine the prevalence and potential determinants of echocardiographically determined LVH in this connection, and to compare 24-h ambulatory blood pressure (BP) recordings with BP measured at a previous clinic visit. METHODS: From a cohort of 120 non-diabetic patients who had been attending a nephrology clinic, 118 agreed to participate in the study. Of these we selected for analysis 85 stable patients (37 male). Patients with known cardiovascular disease, those with a history of poor compliance with antihypertensive medication, and those in whom such medication had been changed in the previous 3 months were excluded. Clinic BP, 24-h ambulatory BP, echocardiography, body mass index (BMI), serum creatinine (SCr), creatinine clearance (CrCl), haemoglobin (Hb), fasting cholesterol (CHOL), triglyceride TRIGL), plasma glucose, calcium (Ca), phosphate (PO4), alkaline phosphatase (ALK PHOS), parathyroid hormone (PTH) concentrations, and 24-h urinary protein were assessed in all patients. Seventy-seven per cent were on antihypertensive medication. RESULTS: LVH was detected in 16% of patients with CrCL > 30 ml/min, and 38% of patients with CrCl < 30 ml/min. By stepwise regression analysis, ambulatory systolic BP (P < 0.0001), male gender (P < 0.0001), BMI (P < 0.0002), and Hb concentration (P < 0.002) were the only independent determinants of left ventricular (LV) mass. Nocturnal systolic BP (P < 0.02) was the main determinant of LVH in the group of patients with advanced CRF. The correlation between left ventricular mass index (LVMI) and mean 24-h ambulatory systolic BP (r = 0.52, 95% confidence interval 0.50-0.54) was statistically significantly stronger than with outpatient systolic BP (r = 0.25, 95% confidence interval 0.23-0.27). The same was true for the correlation between LVMI and mean 24-h ambulatory diastolic BP (r = 0.42, 95% confidence interval 0.40-0.44), and outpatient diastolic BP (r = 0.22, 95% confidence interval 0.20-0.24). CONCLUSIONS: Twenty-four hour ambulatory BP recording and echocardiography are required for accurate diagnosis of inadequate BP control and early LVH in patients with chronic renal impairment, independent determinants of which are hypertension, male sex, BMI, and anaemia.     

Antihypertensive effects of combined lisinopril and hydrochlorothiazide in elderly patients with systodiastolic or systolic hypertension: results of a multicenter trial

This study was aimed at evaluating the antihypertensive effect of lisinopril and hydrochlorothiazide administered in the fixed combination of 20 and 12.5 mg, respectively, on clinic and 24-h blood pressure in elderly patients (age, 68.8 +/- 5.8 years, mean +/- SD) with mild-to-moderate essential systodiastolic or isolated systolic hypertension. After a washout period of 4 weeks, patients received once daily lisinopril combined with hydrochlorothiazide for a 6-week period. At the end of the washout and treatment periods, clinic blood pressure was assessed 24 h after dosing, and 24-h ambulatory blood pressure was monitored, taking blood pressure readings every 15 min. Pretreatment clinic blood pressure was 171.3 +/- 14.0/103.7 +/- 5.1 mm Hg (systolic/diastolic) in the group with systodiastolic hypertension (n = 405) and 179.6 +/- 9.4/83.6 +/- 5.4 mm Hg in the group with isolated systolic hypertension (n = 165). The corresponding 24-h average blood pressures were 144.1 +/- 13.9/88.7 +/- 8.4 mm Hg (n = 114) and 150.7 +/- 15.5/80.8 +/- 9.4 mm Hg (n = 40). Clinic blood pressure was significantly reduced by treatment in both groups. This was the case also for ambulatory blood pressure, which was reduced by 9.6 +/- 0.9%/9.9 +/- 0.9% in systodiastolic and by 11.8 +/- 1.3%/8.5 +/- 1.5% in isolated patients with systolic hypertension (p < 0.05 at least for all differences). The antihypertensive effect was similar in patients older and younger than 70 years. In all groups, it was manifest both during the day and the nighttime and was still significant after 24 h. Thus single daily administration of combined lisinopril-hydrochlorothiazide effectively reduces blood pressure in elderly patients with hypertension.     

Association between blood pressure and circulating hormonal factors with left ventricular mass in patients with essential hypertension older than 55 years of age

BACKGROUND: The prevalence of left ventricular hypertrophy (LVH) is higher in elderly patients with hypertension than in normotensive patients. The factors relationed herewith are not well known. The first purpose was to analyse the relationship between the levels of blood pressure (BP) recorded by ambulatory blood pressure monitoring (ABPM) and the left ventricular mass index (LVMI) in a group of untreated patients older than 55 years with essential hypertension. Our second purpose was to observe the relationship between the concentration of several circulating hormones and the left ventricular mass index. SUBJECTS AND METHODS: The study included 31 untreated patients with mild to moderate essential hypertension and 37 healthy normotensives. Both groups were of similar age, sex and body mass index. We determined for both groups the casual arterial pressure (CAP), ambulatory BP monitoring (ABPM) throughout 24 h, daytime (07.00-23.00 h), nighttime (23.00-07.00 h), left ventricular mass index (LVMI) (following Devereux's formula) and circulating levels of endothelin-1, aldosterone, renine, free adrenaline and noradrenaline. RESULTS: The ILVM in hypertensive patients was 139.6 +/- 35.9 g/m2 and in 124.0 +/- 31.8 g/m2 in normotensive (p < 0.05). The percentage of patients with LVH was 63 and 43%, respectively (p < 0.05). The LVMI in hypertensive patients was correlated with the diastolic CAP (97 +/- 7 mmHg) (r = 0.41; p < 0.05), unlike with the systolic CAP (164 +/- 18 mmHg). The ILVM in normotense patients was not associated neither with the systolic CAP (126 +/- 10 mmHg) nor with the diastolic (79 +/- 6 mmHg). In hypertensive patients we found a slight association between the LVMI and the systolic ABPM (130 +/- 14 mmHg) during nighttime (r = 0.41; p < 0.05). The rest of average ambulatory BP and the hormonal values at study did not show a correlation with the LVMI in both groups. CONCLUSIONS: A slight correlation exists between BP (casual and determined with ambulatory blood pressure monitoring throughout 24 hours) and the left ventricular mass index in mild to moderate untrated hypertensive patients older than 55 years. We did not observe correlations between the circulating levels of endothelin-1, renin, aldosterone, free adrenaline and noradrenaline and the left ventricular mass. The average ventricular mass and the number of subjects with ventricular hypertrophy was significantly increased in hypertensives than in normotensives.     

Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy versus combination therapy

A multinational, double-blind, randomised study was conducted to investigate the efficacy and safety of a low-dose combination of the angiotensin converting enzyme inhibitor, ramipril, and the calcium antagonist, felodipine ER, in 642 patients with mild to moderate hypertension [supine diastolic blood pressure (DBP) = 95-115 mm Hg]. After a 4-week single-blind placebo run-in, patients were randomly allocated to once-daily felodipine extended release (ER; 2.5 mg), ramipril (2.5 mg) or felodipine ER/ramipril (2.5/2.5 mg) for 12 weeks. In the intention-to-treat analysis, mean DBP decreased significantly (p < 0.0001) after felodipine ER, ramipril and the combination (-9.1, -9.8 and -11.4 mm Hg, respectively). The decrease was significantly greater with the combination than with felodipine ER monotherapy (p = 0.02). The number of responding patients (final DBP < or = 90 mm Hg or a decrease of > or = 10 mm Hg) was also higher with the combination than with felodipine ER or ramipril monotherapy (65.1%, 53.1%, 55.7%, respectively). There were no differences between the three groups with respect to the incidence of adverse events overall or those considered treatment-related. There were fewer cases of peripheral oedema with combination therapy than with felodipine ER monotherapy. Thirty-three patients (5.1%) withdrew from the study because of adverse events, but there was no clear pattern with regard to the specific events leading to withdrawal. There were no clinically relevant changes in laboratory or clinical safety variables. Ramipril/felodipine ER 2.5/2.5 mg is an appropriate starting dosage when initiating combination antihypertensive therapy.     

Feasibility of adjuvant chemotherapy for breast cancer patients

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.     

Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertension

OBJECTIVE: To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients. DESIGN AND METHODS: Blood pressure, cardiac rate and the plasma concentrations of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), prostaglandin E2 and 6-keto prostaglandin F1 alpha (the breakdown product of prostacyclin) were determined in the peripheral venous blood of 24 essential hypertensive subjects before and 3 h after administration of 50 mg captopril. Eleven of 24 patients completed a 6-month treatment period with captopril monotherapy (50 mg twice a day). The hemodynamic and hormonal response produced by a last 50 mg dose of captopril was determined once again in the 11 subjects who maintained blood pressure control with captopril monotherapy for 6 months. RESULTS: The fall in blood pressure produced 3 h after drug intake was comparable for the first and the last 50 mg captopril dose. Although the first response to captopril increased plasma levels of Ang I only, the response to the last dose of the drug (6 months after) caused significantly higher levels of Ang I and Ang-(1-7). Neither acute nor chronic therapy with captopril had a significant effect on plasma concentrations of Ang II. Although plasma levels of prostaglandin E2 and 6-keto prostaglandin F1 alpha were not modified by a first exposure to captopril, the concentrations of 6-keto prostaglandin F1 alpha but not prostaglandin E2 rose significantly in subjects treated with the inhibitor for 6 months. A negative correlation was also demonstrated between diastolic blood pressure and plasma Ang-(1-7) levels in the 11 essential hypertensive subjects in whom blood pressure was controlled with captopril monotherapy. CONCLUSIONS: Inhibition of angiotensin converting enzyme with captopril had a significant effect on blood pressure that was not directly accounted for by a suppression of plasma Ang II levels. Continuous therapy with captopril unmasked a contribution of Ang-(1-7) and prostacyclin to the antihypertensive actions of this drug.     

Modification of exercise performance by sharp reduction of blood pressure. A study in patients with uncomplicated hypertension

We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.     

Barnidipine, a novel calcium antagonist for once-daily treatment of hypertension: a multicenter, double-blind, placebo-controlled, dose-ranging study. Dutch Barnidipine Multicenter Study Group

The antihypertensive effects and tolerance of once-daily barnidipine, a novel dihydropyridine calcium antagonist, were evaluated. A total of 190 patients with a sitting diastolic blood pressure (DBP) of 95-114 mmHg were investigated in this multicenter, double-blind, placebo-controlled, dose-ranging study. After a 4-week single-blind placebo run-in period, patients were randomized to placebo or barnidipine (10 mg, 20 mg, or 30 mg modified release capsules) once daily for 6 weeks. Nonresponders (sitting DBP > or =90 mmHg and a decrease of < 10 mmHg) were treated for an additional 6 weeks with a dose increase of 10 mg. At each clinic visit, sitting and standing blood pressure and heart rate were measured approximately 24 hours after the last dose of study drug was taken. Compared with placebo, barnidipine lowered blood pressure, with a trend toward a dose-response relationship over the dose range 10-30 mg. A dose increment of 10 mg in nonresponders resulted in additional reductions in blood pressure. At the end of the active treatment period, the responder rates were 41% and 57% for 10 mg and 20 mg barnidipine, respectively. Heart rate in both sitting and standing positions was not affected by barnidipine. Treatment with barnidipine was well tolerated, and the incidence of adverse events was dose related and consistent with vasodilatation. In conclusion, barnidipine (10-30 mg) administered once daily is well tolerated and reduces blood pressure in patients with mild to moderate hypertension.     

Effects of rilmenidine (hyperium) on lipid balance in hyperlipidemic hypertensive patients. Randomized, controlled, double-blind 8-week study vs. captopril in parallel groups

Rilmenidine (dose of 1 mg once or twice a day) is the first oxazoline compound with antihypertensive properties. Its effects on lipid parameters [total cholesterol, HDL and LDL fractions, triglycerides, apolipoprotein A1 and B, lipoprotein (a)] were compared under double-blind conditions and in parallel groups to those of captopril (50 to 100 mg per day, in 2 divided doses) over a period of 8 weeks, in 51 hyperlipidaemic hypertensive patients [age: 56.3 +/- 1.5 years, systolic and diastolic blood pressure (SBP/DBP): 165.1 +/- 2.0/99.1 +/- 0.6 mmHg, LDL cholesterol: 5.38 +/- 0.16 mmol/L]. No significant difference was demonstrated between the groups on inclusion for any of the clinical parameters (SBP, DBP, heart rate (HR)) and laboratory parameters, apart from apolipoprotein A1, for which the mean value was higher in the rilmenidine group than in the captopril group (p < 0.05). No difference between the groups was demonstrated during the 8 weeks of treatment for the course of blood pressure: SBP and DBP decreased by 20.5 and 13.9 mmHg, respectively, in the rilmenidine group and by 21.3 and 13.1 mmHg in the captopril group (no significant difference: NS). HR decreased by 0.3 beats per minute (bpm) in the rilmenidine group and by 4.1 bpm in the captopril group (NS). No statistically significant difference in lipid parameters was observed between the two groups. No clinically significant variation in any of the lipid parameters was observed after 8 weeks of treatment with rilmenidine or captopril. These results confirm the antihypertensive efficacy and neutrality of rilmenidine on lipid metabolism over a period of 8 weeks. Rilmenidine therefore represents a useful alternative in the first-line treatment of hypertension in hyperlipidaemic hypertensive patients.     

Code Stroke: rapid transport, triage and treatment using rt-PA therapy. The NINDS rt-PA Stroke Study Group

In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.