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This double-blind, multicenter trial compared antihypertensive efficacy, tolerability, and impact on quality of life of manidipine and amlodipine in patients with mild-to-moderate essential hypertension. Patients were randomly assigned to 48 weeks of once-daily manidipine, 10-20 mg, or amlodipine, 5-10 mg. Patients who did not respond to treatment after 12 weeks were also given enalapril, 10-20 mg, for the study's duration. The main efficacy end point was equivalence in sitting systolic (SiSBP) and diastolic (SiDBP) blood pressure reduction between the two drugs after 8 weeks (per protocol analysis). An intention-to-treat (ITT) analysis was performed in all patients with at least one efficacy determination during treatment. Quality of life was assessed by the "Subjective Symptoms Assessment Profile" (SSA-P) and "General Well-being Schedule" (GWBS), after 12 weeks of treatment. SiSBP reduction after 8 weeks was equivalent for manidipine (15.2 mm Hg, n = 227) and amlodipine (17.0 mm Hg, n = 219). The corresponding figure for SiDBP was 11.3 mm Hg for manidipine and 12.3 mm Hg for amlodipine. In the larger ITT population SiDBP was similarly and significantly reduced by manidipine (from 102 +/- 5 to 88 +/- 9 mm Hg, n = 241) and amlodipine (from 101 +/- 5 to 87 +/- 8 mm Hg, n = 240). Similar results were observed for SiSBP and standing SBP and DBP. Neither drug changed sitting or standing heart rate compared with baseline. SSA-P scores improved with manidipine but not amlodipine. GWBS total and partial scores increased more with manidipine than with amlodipine. Safety profile favored manidipine, which was associated with significantly less ankle edema than was amlodipine. This study shows for the first time that long-term treatment with the long-acting calcium channel blocker manidipine is as effective as treatment with amlodipine, has a better tolerability profile, and induces greater improvement in quality of life than amlodipine.

Background: In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown., Methods and Results: In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP., Conclusions: In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.

Diabetic nephropathy is the most frequent cause of chronic renal failure. The onset of microalbuminuria in patients with diabetes mellitus, which seems to be related to blood pressure and the control of glycemia, is predictive of the development of true proteinuria. This multicenter, single-blind, randomized study examined the effects of benazepril and nicardipine on overnight microalbuminuria in 57 normotensive and 46 hypertensive diabetic patients. At the end of a 3-month placebo run-in period, the patients were stratified on the basis of the presence or absence of arterial hypertension and, within each stratum, randomized to receive one daily tablet of 10 mg benazepril or one tablet of 20 mg nicardipine twice daily for 6 months. Renal hemodynamics was investigated in 25 patients. Both drugs decreased overnight microalbuminuria throughout the study period, but benazepril was more effective than nicardipine (p = 0.025); in the patients with hypertension, both drugs led to a similar marked reduction in systolic and diastolic blood pressure. This study shows that benazepril was more effective than nicardipine in reducing overnight microalbuminuria in patients with diabetes mellitus, independently of their antihypertensive properties.

Many patients with arterial hypertension have abnormal urinary excretion levels of albumin. This study was aimed at examining the effects of lisinopril and amlodipine on urinary excretion of albumin and kidney function. Thirty-six previously untreated patients with essential arterial hypertension were divided randomly into two groups. The first group received lisinopril 20 mg daily for 12 weeks followed by 10 mg amlodipine daily for another 12 weeks. The second group received 10 mg amlodipine daily for 12 weeks followed by 20 mg lisinopril daily for another 12 weeks. The arterial pressure decreased in a similar way with both therapies in both groups. In both groups urinary albumin excretion decreased in patients receiving lisinopril (p < 0.01). No significant changes were observed with amlodipine. This study shows that lisinopril, but not amlodipine, is able to reduce urinary excretion of albumin in patients with essential hypertension independently of its effective antihypertensive properties. It is probable that the positive effect of lisinopril on microalbuminuria is attributable to the modifications in intrarenal hemodynamics or to a change in glomerular permeability.

The use of ambulatory blood pressure monitoring in clinical studies offers some advantages in comparison to the clinic blood pressure measurement. In fact, this approach does not induce any alerting reaction and provides 24-h blood pressure values that are more reproducible and not affected by the placebo effect. This allows a better evaluation of blood pressure under antihypertensive treatment and an optimization of the number of patients to be studied in pharmacologic trials. In a recent double-blind, parallel-group study, ambulatory blood pressure monitoring was used to investigate the antihypertensive efficacy of a new angiotensin-converting enzyme inhibitor, trandolapril, in 62 mild and moderate hypertensive patients. After a washout period, patients received trandolapril, 2 mg o.d., or placebo for 6 weeks, followed by a second washout period. Clinic and 24-h blood pressures were assessed at the end of each period. In comparing the pre- and post-treatment period, trandolapril significantly reduced clinic and 24-h systolic and diastolic blood pressures. The fall was evident throughout the 24 h and was statistically significant also in the last 4 h of blood pressure monitoring. The placebo group did not show any significant blood pressure change. Thus, trandolapril, 2 mg once daily, is effective in reducing blood pressure. Its efficacy over 24 h is better documented by 24-h blood pressure monitoring than by isolated clinic blood pressure measurement.

The anti-hypertensive activity and influence on some forms of stress of slow-release Nicardipoine and Captopril were compared using a randomized 2:1 protocol. Thirty-six patients, mean age 55.9 years, suffering from slight or moderate arterial hypertension were treated with either 40 mg of Nicardipine retard twice a day (b.i.d.), or Captopril in a dose of 25 mg (b.i.d.) for 8 weeks. A significant reduction was observed in arterial pressure, both in orthostatism and clinostatism, following both treatments in comparison to the placebo period, but the group treated with slow-release Nicardipine showed a greater and statistically significant reduction in arterial pressure. No significant change in heart rate was reported using either drug. Non-invasive out-patient monitoring of arterial pressure, performed using Spacelabs 5300, showed a significant reduction in arterial pressure using both drugs and the conservation of the normal circadian rhythm of arterial pressure. The pressure response to the cold pressor test (CPT), mental arithmetic test (MAS), and to dynamic and isometric effort was positive with both drugs, thus revealing a degree of protection offered by treatment using these two substances. In overall terms, the two drugs were well tolerated.

Thirty-six patients (17 males and 19 females), aged between 40 and 70 years old (mean age 55.9), suffering from slight or moderate arterial hypertension, were monitored for four weeks after 14 days of placebo treatment. In a double-blind and random study 24 patients were treated with Nicardipine Retard (40 mg twice a day) whereas a further 12 received placebo twice a day. Sphigomanometric controls carried out after two and four weeks showed a significant reduction in arterial pressure only in those patients receiving active treatment. 24-hour out-patient monitoring of arterial pressure, carried out using Spacelabs 5300, showed a reduction in both systolic and diastolic arterial pressure throughout the day in subjects treated with calcium-antagonists compared to the placebo group. The normal physiological 24-hour trend of arterial pressure was always taken into account. The pressure response to a cold pressor test, mental arithmetic test, isometric and dynamic effort tests, measuring using a cycloergometer, was not modified by anti-hypertensive treatment, thus confirming the preservation of normal physiological behaviour during daily activities. There was no significant change in heart rate and the drug was well tolerated.

The aim of the study was to evaluate the efficacy of enalapril and atenolol in decreasing the severity of proteinuria in hypertensive patients suffering from insulin-dependent diabetes mellitus. We studied 20 hypertensive patients. All patients had proteinuria (> 3 g/24 h) and were receiving insulin treatment. Proteinuria was measured monthly in the run-in period (3 months) and during the active drug treatment (8 months). Glomerular filtration rate, effective renal plasma flow, filtration fraction, and total renal resistance were determined after the run-in and treatment periods. The patients were randomly assigned to treatment with enalapril 20 mg/day or atenolol 100 mg/day for 8 months. In both groups blood pressure decreased significantly. After 8 months' treatment, severity of proteinuria significantly decreased both in the enalapril-treated group and in the group receiving atenolol. Glomerular filtration rate and effective renal plasma flow significantly increased, while total renal resistance decreased in the patients given enalapril, whereas glomerular filtration rate, renal plasma flow, and total renal resistance significantly decreased in the patients given atenolol. The results of this study show that enalapril and atenolol reduce proteinuria in hypertensive diabetic patients by a mechanism related to their antihypertensive effects; furthermore, the beneficial effects of enalapril might be also linked to intrarenal effects.

Fifty patients with mild or moderate hypertension were assessed for the influence on peripheral hemodynamics of 10 months of treatment with lisinopril (25 patients) or metoprolol (25 patients). Two-dimensional Doppler flowmetry was used for the evaluation. Responding patients (blood pressure < 150/90 mm Hg) were monitored for another 4 weeks after treatment withdrawal to determine whether changes in forearm hemodynamics, if any, persisted. Twenty-two patients from either group (88%) were considered to be responders. Systolic and diastolic blood pressure in patients receiving lisinopril dropped by 6% and 15%, respectively (p < 0.001), in those receiving metoprolol the decrease was 5.9% and 14%, respectively (p < 0.001). Forearm hemodynamics was not significantly different before treatment and improved in patients receiving lisinopril, with increased compliance (p < 0.001) and lower vascular resistance (p < 0.001). No significant changes were observed with metoprolol. After withdrawal, blood pressure returned to baseline values in both groups. However, improvement in forearm hemodynamics persisted in the lisinopril group. Hemodynamics changes were statistically different on lisinopril versus metoprolol both after treatment and after withdrawal. Lisinopril, but not metoprolol, seems capable to induce regression of functional and/or structural changes of large arteries in patients with hypertension.

Various aspects of carbohydrate and lipid metabolism were studied in two groups of patients with mild hypertension before and after 6 months' treatment with either lisinopril (n = 10) or hydrochlorothiazide (n = 10). A significant reduction of arterial blood pressure was seen after both treatment regimens. Circulating plasma glucose, insulin, C-peptide and triglyceride concentrations were measured at hourly intervals from 8.00 a.m. to 5.00 p.m. in patients on an isocaloric diet (35 cal/kg/day). Plasma glucose concentrations remained unchanged, while insulin and C-peptide concentrations were higher in association with hydrochlorothiazide treatment. Conversely, lisinopril-treated patients had lower C-peptide concentrations after treatment. The changes in daylong plasma glucose and insulin-stimulated glucose uptake increased after hydrochlorothiazide treatment and decreased following lisinopril. Lastly, plasma cholesterol concentrations did not change after lisinopril therapy, whereas plasma high density cholesterol decreased as a result of hydrochlorothiazide treatment.

The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

This study used 2D Doppler flowmetry to assess the effects on peripheral hemodynamics of effective treatment with nicardipine or atenolol in 40 patients with mild or moderate essential hypertension. Two groups of 20 patients received treatment with nicardipine or atenolol, respectively, for 8 months. Consequently, those patients considered to be responders (blood pressure less than 150/90 mm Hg) were monitored for another 4 weeks after the therapy was suspended in order to determine whether the changes, if any, in arterial compliance persisted. Following the 8-month therapy, four patients from each group were excluded from the study because of unsatisfactory blood pressure levels. After the treatment, there was a decrease in blood pressure in both groups (P less than .01). In the nicardipine group, there was a significant increase in diameter and compliance (P less than .01), whereas pulse wave velocity and resistance decreased (P less than .01). In the atenolol group, these parameters did not change significantly. After therapy was ended, blood pressure returned to baseline values in both groups. However, in the nicardipine group, the observed improvement in forearm hemodynamics persisted. This result may indicate that nicardipine is able to induce a regression of functional and/or structural changes in the large arteries of hypertensive patients.

The risk of cardiovascular morbidity and mortality is greatly affected by cigarette smoking. In order to study the pressor response to smoking, 10 normotensive and 10 mild or moderate essential-hypertensive smokers (> 20 cigarettes daily) were compared with 2 comparable groups of non-smokers. All subjects were asked to smoke 4 cigarettes during 1 h; blood pressure (BP) and heart rate (HR) were monitored beat-to-beat by a non-invasive device (Finapres Ohmeda) during the smoking period and during the immediately preceding non-smoking hour. Furthermore, all subjects underwent 24-hour ambulatory BP monitoring. In all groups, each cigarette induced a similar and statistically significant increase from baseline for both BP and HR. The recovery from the marked rise in BP and HR was very slow so that in the smoking hours BP and HR were persistently higher than in non-smoking hours; there were no statistically significant differences between the four groups. During 24-hour ambulatory monitoring both normo- and hypertensive smokers showed higher BP values and higher BP variability in comparison with the respective non-smokers' group. In conclusion, smoking habits were associated with a persistent increase in BP in each group we studied, possibly contributing to a smoking-related cardiovascular risk.

Various aspects of carbohydrate and lipid metabolism have been studied in two groups of patients with mild hypertension before and after six months of treatment with either nicardipine (n = 10) or metoprolol (n = 10). A significant reduction of the arterial blood pressure was seen with both treatment regimens. Circulating plasma glucose, insulin, C peptide and triglyceride concentrations were measured at hourly intervals from 08 h 00 to 17 h 00, in patients on an isocaloric diet (35 kcalth/kg/die). Plasma glucose concentrations were unchanged and insulin and C peptide concentrations were higher in association with metoprolol treatment. In contrast, nicardipine-treated patients had similar plasma insulin, but lower plasma glucose, C peptide and triglyceride concentrations after treatment. The changes in day-long plasma glucose and insulin-stimulated glucose uptake had increased in association with metoprolol treatment and decreased following nicardipine. Finally plasma cholesterol concentrations did not change following metoprolol therapy, whereas plasma high density lipoprotein cholesterol increased in association with nicardipine treatment. The data seem to indicate that the negative effect of nicardipine on secretion of insulin is balanced by an improvement in glucose uptake.

The aim of the study was to compare efficacy and safety of quinapril and lisinopril once-daily administered in patients with mild to moderate hypertension. After a two-week placebo period, 23 patients with sitting diastolic blood pressure between 95 and 110 mmHg were randomly assigned to the therapy with quinapril 20 mg/die or lisinopril 10 mg/die for 4 weeks in a single-blind design. After 4 weeks patients with diastolic blood pressure greater than 90 mmHg were treated with a higher dose (lisinopril 20 mg/die; quinapril 40 mg/die). Therapy with lisinopril normalized 83% of patients, and quinapril 45% of patients. Lisinopril was significantly better than quinapril in reducing blood pressure after 4 and 8 weeks of active treatment. The 24 hours ambulatory blood pressure monitoring showed that quinapril failed to control blood pressure after 12 hours from the administration of the drug.

We have measured the blood pressure to 1500 children aged between 6 and 14 years by sphingomanometric method, using various cuffs according to the recommendations of the A.H.A. Systolic and diastolic pressure was taken and the average value and standard deviations were calculated for each age. On the ground of the values equal or higher than 97 degrees percentil was the presence of 99 subjects afflicted with not secondary hypertension. We noticed that blood pressure increases with the age, is independent of sex, but bears relationship to the presence of obesity (out of 72 obese subjects, 25 were afflicted with hypertension), of menarca (17 hypertensive menstruated out of 27) and of family hypertension (31 hypertensive parents out of 41 examined). Neither relation was found between children's hypertension and socio-economical level nor between hypertension and presence of pathological proteinuria.

In spite of the widespread use of intravenous urography and its extensive employment in the study of hypertension, there is still no unanimity of views as to its application in such pathology. 147 urographies belonging to 330 hypertense patients admitted to the Bari Medical Pathology Department between 1-1-1975 and 30-9-1977 have therefore been examined so as to assess its diagnostic value. Thereafter, the percentage of abnormalities found with urography were evaluated and compared with those in the population at large. Results stress on the one hand the higher incidence of renal ptosis and poly-cystic kidneys in the hypertense, and also highlight the possibility of revealing clinically silent diseases with this technique; on the other hand, many urographies (more than 50%) were useless and it is not always possible to diagnose certainly the presence of stenosis of the renal artery owing to the presence of false positives and negatives.

Thirty hypertensive diabetic patients were randomly, double blindly, treated with Captopril (CPT) 50 mg + hydrochlorothiazide (HCTZ) 15 mg (No 19) or HCTZ 25 mg alone (No 11) for 3 months, to assess blood pressure control and some metabolic modifications. The results indicate that CPT + a low dose of HCTZ maintains the synergistic effect of the two drugs, minimizing the metabolic problems related to HCTZ in hypertensive diabetic patients.

It is well recognized that the co-administration of some drugs to persons receiving digoxin results in an increase of serum digoxin levels: it occasionally precipitates digoxin toxicity. There are some possible mechanisms by which different drugs may increase serum glycoside levels: 1) by displacing digoxin from tissue binding sites, 2) by decreasing digoxin renal excretion, 3) by enhancing digoxin absorption, 4) by increasing the inhibition of the ATP-dependent pump. Combined administration of calcium antagonists and B-methyldigoxin is common in patients with heart diseases. Other Authors have found that the co-administration of these drugs with digoxin increases glycoside serum levels, without signs of intoxication. We have examined the effects of this combination on digitalis activity, by Rubidium 86 uptake in erythrocytes. Thirty patients aged 52 to 66 with congestive heart failure were studied. All of these had normal serum creatinine, blood urea and serum protein levels. These subjects received 0,20 mg of B-methyldigoxin daily for nine days; afterwards, ten of them were given in addition 320 mg of verapamil for seven days; the other ten received in addition 60 mg of nifedipine, for seven days; the remaining ten patients received in addition 320 mg of verapamil and 60 mg of nifedipine together, for seven days. Digoxin activity was measured on the eighth, ninth and sixteenth day of treatment by Rubidium 86 uptake in erythrocytes. The technique was that of Bertler. Means were compared with the t test, with the assumption of the equal variances in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Digoxin and Verapamil may often be used in association in heart diseases; we tested whether this coadministration increases digitalis activity. Ten patients with failing heart were given 0.10 mg of beta-methyldigoxin, twice a day, for nine days; then they received in addition 80 mg of Verapamil, four times a day, for seven days. Digoxin activity was measured on the eighth, ninth and 16th days of treatment by 86Rubidium uptake in erythrocytes. The steady-state concentration was 0.91 +/- 0.13 ng/ml; during the coadministration the concentration rose to 1.23 +/- 0.16 ng/ml (an increase of 35.12%). The change was significant (p less than 0.001). The mechanism of this increase is unknown: it is important that there exists an increase in digitalis activity and not only a haematic elevation.

Changes in arterial blood pressure and in thermographic values were evaluated in two groups of 15 hypertensive patients, each of which was treated, on a random basis, with a combination of atenolol plus chlorthalidone or a combination of labetalol plus chlorthalidone. Both combinations produced a statistically significant reduction in blood pressure values (p less than 0.01) with no changes in heart rate. Telethermographic investigations revealed the presence of hypothermia of the hands before treatment in all the hypertensive patients examined, but not in the control group (10 normal subjects with no vascular and/or hyperthermic disease). After one month of treatment, no changes in peripheral vascularization were observed in the group treated with atenolol plus chlorthalidone, except for 4 cases showing mild improvement, probably due to a reduction in peripheral resistance as a result of the treatment and to a consequent increase in blood flow in the area investigated. In the group treated with labetalol plus chlorthalidone, on the other hand, a substantial recovery of vascular flow was observed in 12 patients as a result of the treatment, while the remaining 3 patients showed a fair degree of improvement (2 degrees C). Both preparations lent themselves to simplified administration regimens with good patient compliance and no adverse reactions.

ECG traces from 60 children aged 10-14 yr with hypertension were examined to see whether this condition itself was enough to alter the parameters in a statistical comparison with the traces for 19 normotensive children of the same age. Some statistically significant differences were noted in: the deviation of the P wave axis, increased left ventricle activation time, frequency and QTc segment, presence of anticlockwise rotation on the longitudinal plane and junctional rhythms. These support the view that changes in these parameters is not dependent on the concomitance of other diseases, but due to hypertension itself.