Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients.

The aim of this study was to evaluate the effect of benazepril addition to amlodipine antihypertensive treatment on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. A total of 32 mild to moderate essential hypertensives (DBP>90 and <110 mmHg), aged 30-70 years were studied. After a 4-week placebo period, they were randomized to amlodipine 5 mg o.d. or benazepril 10 mg o.d. or amlodipine 5 mg plus benazepril 10 mg o.d. for 4 weeks, according to a crossover design. At the end of the placebo period and of each active treatment period, blood pressure,AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed using a system, the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and benazepril monotherapy significantly reduced SBP (-18.2+/-4 and -17.8+/-4 mmHg, respectively, P<0.01 vs baseline) and DBP (-12.1+/-3 and -11.7+/-3 mmHg, respectively, P<0.01); the reduction was increased by the combination (-24.2+/-5 mmHg for SBP, P<0.001 and -16.8+/-4 mmHg for DBP, P<0.001). Amlodipine monotherapy significantly increased both AFV (+17.1%, P<0.001 vs baseline) and PSTP (+56.6%, P<0.001 vs baseline). As compared to amlodipine alone, the combination produced a less pronounced increase in AFV (+5.5%, P<0.05 vs baseline and P<0.01 vs amlodipine) and PSTP (+20.5%, P<0.05 vs baseline and P<0.01 vs amlodipine). Ankle oedema was clinically evident in 11 patients with amlodipine monotherapy and in three patients with the combination. These results suggest that ACE-inhibitors partially counteract the microcirculatory changes responsible for Ca-antagonists-induced oedema formation.

Community control of hypertension at work-site: epidemiological data of the Agusta project.

In order to set up a program of community control of hypertension at the work site, 8811 employees belonging to 12 factories of the same company (Agusta SpA, Italy) were screened. Seven hundred and seventy-two subjects (8%) were found to be hypertensive; 48% of them were hypercholesterolemic, 44% were smokers, 5% presented with hyperglycemia and 4% had left ventricular hypertrophy. Multiple regression analysis showed a significant correlation between hypertension and age, hypercholesterolemia, body mass index, occupational exposure to noise exceeding 80 dB and, below the age of 40 years, the type of job. Seven hundred and twenty-nine hypertensives were assigned to pharmacological treatment. This group of patients will be followed up for 3 years.

Effects of different antihypertensive drugs on plasma fibrinogen in hypertensive patients.

1. In order to evaluate whether treatment with different antihypertensive drugs would affect plasma fibrinogen levels, 118 mild to moderate essential hypertensive subjects, all males, aged 18 to 65 years, were randomly treated with amlodipine 10 mg, atenolol 100 mg, hydrochlorothiazide 25 mg or lisinopril 20 mg, all given once daily for 8 weeks. 2. Before and after 8 weeks' treatment, blood pressure (BP), heart rate (HR), fibrinogen, total cholesterol (TC), HDL-C, LDL-C, triglycerides (TG), plasma glucose, plasma uric acid, serum creatinine and serum potassium were evaluated. 3. All four medications significantly reduced BP values, although the BP lowering effect of lisinopril, amlodipine and atenolol was significantly greater compared with that of hydrochlorothiazide. 4. Plasma fibrinogen levels were unaffected by atenolol, hydrochlorothiazide and amlodipine, whereas they were significantly decreased by lisinopril (-11.2%, P = 0.002). This fibrinogen lowering effect was more evident in smokers (-17.7%) than in non smokers (-7.4%). 5. Atenolol and amlodipine did not significantly affect plasma lipids, hydrochlorothiazide increased TC, LDL-C and TG and reduced HDL-C; lisinopril increased HDL-C and decreased TC and LDL-C. 6. Hydrochlorothiazide increased plasma glucose and uric acid concentrations, which were unaffected by the other drugs. The diuretic also reduced serum potassium. 7. The results of this study indicate that lisinopril reduces levels of plasma fibrinogen and confirm that different antihypertensive drugs may elicit different metabolic effects, which may variously influence the overall risk profile of the hypertensive patients.

Urinary albumin excretion and nocturnal blood pressure in hypertensive patients with type II diabetes mellitus.

The aim of this study was to evaluate the relationship between nocturnal blood pressure (BP) (by ambulatory blood pressure monitoring, ABPM) and urinary albumin excretion (UAE) in hypertensive patients with type II diabetes mellitus. We studied 179 essential hypertensives (WHO I-II), all males, with non-insulin-dependent diabetes. Non-invasive ABPM was performed by a fully automatic, portable device (Spacelabs 90202), set to take readings at 15-min intervals during both day-time 7 AM to 1 PM and nighttime (1 PM to 7 AM). According to the day/night reduction in mean blood pressure (MBP), three groups were identified: group I, nocturnal MBP reduction > 10%; group II, day/night MBP reduction of 5% to 10%; and group III, day/night MBP reduction < 5%. The mean values of UAE as well as the prevalence of microalbuminuria (UAE > 30 mg/24 h) were found to be significantly higher in group III as compared to the other two groups. Besides, in group III UAE displayed a significant negative relationship with the SBP and MBP (but not DBP) nocturnal drop and a positive relationship with the duration of hypertension and duration of diabetes. In group II, UAE was weakly correlated only with the duration of hypertension, whereas in group I no significant correlation was found between UAE and other parameters of the study. These results indicate that in hypertensive type II diabetic patients a blunted nocturnal BP fall is associated with higher UAE and increased prevalence of microalbuminuria. Whether the reduced day/night BP difference is the cause of consequence of target organ damage remains to be established.

Fibrinogen levels in normotensive and hypertensive men: a cross-sectional study.

BACKGROUND: The aim of this study was to compare plasma fibrinogen levels in hypertensive and normotensive men. Possible confounding factors, such as age, cholesterol levels, body-mass index and smoking habits were also to be considered. METHODS: We studied 708 men with essential hypertension (according to the World Health Organization's criteria) and 944 with normal blood pressures, all of whom had similar lifestyles; the overall age range was 18-60 years. The clinical evaluation included measurements of blood pressure, heart rate, body weight and height as well as a medical examination and personal habits history. After an overnight fast, blood samples were taken in order to measure fibrinogen and total-cholesterol levels. RESULTS: The mean fibrinogen level did not differ between the groups, although the distribution of the levels was different and was J-shaped in the hypertensive group. Plasma fibrinogen levels increased significantly with age in both groups. A significant positive correlation was found between fibrinogen and total-cholesterol levels, but not between fibrinogen and body-mass index or systolic or diastolic blood pressures. Cigarette smokers had significantly higher fibrinogen levels than non-smokers, irrespective of their blood pressure status; ex-smokers had intermediate values, suggesting a direct but reversible effect of tobacco. In cigarette smokers, fibrinogen levels increased with the number of cigarettes smoked, which is indicative of a dose-response relationship. CONCLUSION: This study confirms the strong association between fibrinogen levels and smoking and the weaker association with age and total-cholesterol levels. Mean fibrinogen level was not significantly related to blood pressure, although the distribution of fibrinogen levels appeared to be J-shaped in hypertensive men.

Ambulatory blood pressure monitoring in normotensive and hypertensive type 2 diabetes. Prevalence of impaired diurnal blood pressure patterns.

To assess the prevalence of an impaired diurnal blood pressure (BP) pattern in a population of both normotensive and hypertensive diabetics, noninvasive ambulatory BP monitoring (SpaceLabs 5200, Redmond, WA) was performed in 96 outpatients with type 2 diabetes (47 normotensives and 48 hypertensives) and in 103 control subjects without diabetes (50 normotensives and 53 hypertensives). Mean 24 h and daytime (06:00 to 22:00) BP and heart rate (HR) were not statistically different in diabetic patients compared to nondiabetic ones. Nighttime (22:00 to 06:00) BP and HR tended to be higher in both normotensive and hypertensive diabetics, although not significantly. Heart rate, diastolic BP (DBP), and especially the nocturnal systolic BP (SBP) decrease, were less marked in both normotensive and hypertensive diabetics, with a consequent increase in rate-pressure. A significant correlation was found between the percent decrease in nighttime SBP and the decrease in orthostatic SBP in casual BP measurements. The analysis of individual recordings allowed us to detect an impaired circadian pattern (the disappearance of the nocturnal BP decrease or a paradoxical BP increase) in 30% of the normotensive and 31% of the hypertensive diabetics (v 6% of the normotensive and 6.4% of the hypertensive nondiabetic subjects). As the absence of a nocturnal BP fall has been associated with the increased prevalence of left ventricular hypertrophy and atherosclerotic cardiovascular disease, its detection by ambulatory monitoring might be of prognostic and therapeutic importance.

Comparison of bisoprolol and diazepam in the treatment of cardiac neurosis.

In order to compare the beta blockers bisoprolol and diazepam in the treatment of cardiac neurosis, 40 patients (16 males and 24 females, mean age: 39 +/- 11 years) were examined in a double-blind, crossover study. Following a 4-week placebo period, patients were randomized to receive either bisoprolol 10 mg daily or diazepam 5 mg twice daily for 4 weeks. After a second 4-week washout period on placebo, patients were switched to the alternative regimen for a further 4 weeks. At the end of the placebo periods and during each phase of treatment, the following parameters were evaluated: somatic symptoms by self-assessment questionnaire, anxiety state by Hamilton rating scale, reaction time to both acoustic and visual stimuli, blood pressure, and heart rate. Both treatments were effective in reducing somatic symptoms of cardiac neurosis, but bisoprolol was significantly more effective than diazepam (p less than 0.01). On the contrary, diazepam was superior to bisoprolol in improving the Hamilton scale related to psychic symptoms. Only diazepam prolonged reaction times. Both treatments were well tolerated; however, 12 patients complained of drowsiness and nine of sedation under diazepam. In conclusion, bisoprolol appeared to be as effective as diazepam in the treatment of cardiac neurosis, but with better effects on somatic symptoms and without affecting patients' psychomotor performance.

Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study.

Prostaglandins (PG) have been suggested to play a role in the genesis of cough induced by angiotensin-converting enzyme inhibitors (ACE-I) and that inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Moreover, experimental and clinical data suggest that nifedipine, a dihydropyridine Ca antagonist, can inhibit PG synthesis. Therefore, we wished to determine whether nifedipine can reduce cough induced by ACE-I as compared with indomethacin, a known inhibitor of PG synthesis. Fourteen hypertensive patients who developed cough during captopril chronic therapy randomly received slow-release nifedipine 20 mg twice daily (b.i.d.), indomethacin 50 mg b.i.d., and placebo b.i.d. for 1 week in a double-blind, cross-over design. At the end of each treatment phase, cough was evaluated by a self-administered questionnaire containing an ordinal scale for daily cough intensity and frequency. Indomethacin abolished or markedly reduced cough induced by ACE-I, whereas nifedipine reduced it but to a lesser degree. These findings suggest that PG can play a role in cough caused by ACE-I, and a dihydropyridine Ca antagonist can reduce the occurrence of this side effect.

Nitrendipine 20 mg once daily versus nicardipine slow release 40 mg twice daily in mild essential hypertension: evaluation by 24-hour ambulatory blood pressure monitoring.

The extent and duration of the blood pressure (BP) lowering effect of 20 mg nitrendipine (NIT) once daily and 40 mg nicardipine slow release (NIC) twice daily were compared in 12 men (aged 39-55 years) with mild essential hypertension according to a randomized, cross over study. Twenty-four-hour non invasive ambulatory BP monitoring (Spacelabs 5200) was performed at the end of a 2-week placebo run-in and after 4 weeks of each active treatment; automatic BP measurements were programmed at 15-min intervals. Both treatments significantly (p less than .01) reduced mean 24-hour and daytime systolic (SBP) and diastolic (DBP) BP, but had different effects on daytime BP profiles. NIT decreased SBP and DBP (p less than .05) in 5 out of 8 two-hour subperiods (from 8 a.m. to 6 p.m.), followed by a loss of effect; NIC reduced SBP and DBP (p less than .05) in 7 out of 8 two-hour subperiods (from 8 a.m. to 10 p.m.). During the night-time, NIT reduced mean SBP (p less than .05) and NIC both mean SBP and DBP values (p less than .05; p less than .05 vs NIT for SBP). Heart rate was not affected by either treatment. Thus, after short-term treatment in mild essential hypertensives nitrendipine once daily was not as effective as nicardipine slow release twice daily in reducing blood pressure throughout the 24 hours.

Effects of calcium channel blockers on cardiovascular responses to smoking in normotensive and hypertensive smokers.

To evaluate the effects of short- and long-term administration of calcium (Ca) entry blockers on cardiovascular responses to cigarette smoking, 28 normotensive and 26 hypertensive smokers were studied. According to a double-blind, cross-over design, normotensive smokers were given a single dose (10 mg) of isradipine or a placebo and were checked before and after dosing. After a four-week period on a placebo, hypertensive smokers were treated with slow-release nicardipine 40 mg twice daily for six months and were checked at the end of the placebo period, after the first dose of nicardipine and at the end of six months of therapy. In both groups, blood pressure and heart rate were monitored by a Takeda TM 2420 non-invasive device every 3 min for 2 h. During the first hour patients were not allowed to smoke, during the second hour they were asked to smoke one cigarette every 15 min. In both normotensive and hypertensive smokers, calcium entry blockers produced a significant attenuation of the rise in blood pressure induced by cigarette smoking. Such effect was more evident after long-term therapy. Acceleration of the heart rate due to smoking was not significantly affected by the administration of Ca-antagonists, although a tendency towards a lesser heart rate increase was observed, particularly after long-term treatment. It was concluded that calcium entry blockers, reducing blood pressure variability, which bears a positive relationship with target organ damage, might be useful in the treatment of hypertensive smokers who were unwilling or unable to stop smoking.

[Functional anatomy of the left ventricle in hypertensive subjects. Correlations with the clinical severity of hypertension]. / Anatomia funzionale del ventricolo sinistro in soggetti ipertesi. Correlazioni con la gravità clinica dell'ipertensione.

Using computerized M-mode echocardiography we have investigated 58 hypertensive subjects in order to assess whether a correlation could be demonstrated between left ventricular changes induced by hypertension and age of the patients, the duration and severity of hypertension, and damage to other target organs. Various morphological changes of the left ventricle were detected: 14 patients (24%) had concentric hypertrophy of the left ventricle, 12 (20%) had asymmetric septal hypertrophy, 5 (8%) had dilated left ventricle without hypertrophy. Left ventricular mass was increased, when compared to normal controls in 24 patients (41%). With respect to functional abnormalities, the peak lengthening rate of left ventricular dimension in diastole was decreased (+dD/dt less than s-1) in 25 patients (43%). Eight of these patients (14%) also had depressed peak shortening rate of left ventricular diameter in systole (-dD/dt less than 1.9 s-1). Hypertensive retinopathy was present in 23 patients (39%) and impairment of renal function in 8 (14%). Left ventricular mass and systolic and diastolic parameters of left ventricular function did not correlate significantly either with the age of the patients, or with the duration and severity of hypertension, or with the damage present in target organs other than the heart. Left ventricular mass was inversely correlated with the index of left ventricular relaxation (r = -0.53; P less than 0.001), whereas neither the latter nor left ventricular mass were correlated with peak systolic stress. Instead, peak systolic stress was inversely correlated with peak shortening rate of left ventricular diameter, an index of systolic function (r = -0.50; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The ultrastructural localization of factor VIII-antigen in human platelets, megakaryocytes and endothelial cells utilizing a ferritin-labelled antibody.

By means of electron microscopy combined with the use of monospecific anti-factor VIII-antigen (VIIIR:AG) antibodies conjugated to ferritin, the subcellular localization of VIIR:AG in platelets, megakaryocytes and in endothelial cells has been established. The reported results suggest the possibility that the megakaryocyte is able to synthesize VIIIR:AG and also to secrete it by means of a microcanalicular system similar to that present in the endothelial cell. Platelets may derive their VIIIR:AG content partly from the megakaryocyte and partly from the plasma.