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.

Transient but not sustained blood pressure increments by occupational noise. An ambulatory blood pressure measurement study.

OBJECTIVE: Studies on the effects of chronic exposure to industrial noise on clinic blood pressure (BP) at rest have yielded inconsistent results. The aim of this study was to evaluate the effect of occupational noise exposure on ambulatory blood pressure (ABP) in normotensive subjects. METHODS: We studied 476 normotensive workers, aged 20-50 years (systolic blood pressure (SBP) < 140, diastolic blood pressure (DBP) < 90), at a metallurgical factory; 238 were exposed to high levels of noise (> 85 dB), while 238 were not exposed (< 80 dB). Clinical evaluation included measurements of casual BP (by standard mercury sphygmomanometer, Korotkoff sound phase I and V) and heart rate (HR) (by pulse palpation), body height and weight. All subjects underwent a 24 h non-invasive ABP monitoring (by SpaceLabs 90207 recorder; SpaceLabs, Redmond, Washington, USA) twice within 14 days: one during a normal working day and one during a non-working day. Measurements were performed every 15 min. Computed analysis of individual recordings provided average SBP, DBP and HR values for 24 h, daytime working hours (0800-1700 h), daytime non-working hours (1700-2300 h) and night-time (2300-0800 h). RESULTS: No significant difference in clinic SBP, DBP and HR was observed between exposed and non-exposed subjects. Results obtained by ABP monitoring showed in the exposed workers: (a) a higher SBP (by a mean of 6 mmHg, P < 0.0001 versus controls) and DBP (by a mean of 3 mmHg, P < 0.0001) during the time of exposure and the following 2 or 3 h, whereas no difference between the two groups was found during the non-working day; (b) an increase in HR, which was present not only during the time of exposure to noise (+3.7 beats-per-minute (bpm), P < 0.0001 versus controls), but also during the non-working hours (+2.8 bpm, P < 0.001) and during the day-time hours of the non-working day (+2.8 bpm, P < 0.003); (c) a significant increase in BP variability throughout the working day. CONCLUSIONS: These findings suggest that in normotensive subjects below the age of 50 years, chronic exposure to occupational noise is associated with a transient increase in BP, which is not reflected in a sustained BP elevation. The possible role of repeated BP and HR fluctuations due to frequent and prolonged exposure to noise in accounting for the higher prevalence of hypertension reported in noise-exposed workers above age 50 years, requires longitudinal studies to be clarified.

Attenuation of the "white-coat effect" by antihypertensive treatment and regression of target organ damage.

This study assessed whether 2 common surrogate measures of the "white-coat effect," namely the clinic-daytime and the clinic-home differences in blood pressure (BP), were attenuated by long-term antihypertensive treatment and whether this attenuation is relevant to the treatment-induced regression of left ventricular hypertrophy, thus having clinical significance. We considered data from 206 patients with essential hypertension (aged 20 to 65 years) who had a diastolic BP between 95 and 115 mm Hg and echocardiographic evidence of left ventricular hypertrophy. In each patient, clinic BP, 24-hour ambulatory BP, and left ventricular mass index were assessed at baseline, after 3 and 12 months of treatment with an angiotensin-converting enzyme inhibitor, and after a final 4-week placebo run-off period. At baseline, the clinic-daytime differences in systolic and diastolic BP were 12.1+/-15.4 and 6.8+/-10.1 mm Hg, respectively; the corresponding values for the clinic-home differences were 5.7+/-10.6 and 2.9+/-6.1 mm Hg, respectively. These differences were reduced by 57.6% and 77.1% (P<0.01) and by 65.7% and 64.3% (P<0.01), respectively, after 12 months of treatment, with a partial return toward the pretreatment differences after the final placebo period. The observed treatment-induced reductions in left ventricular mass index and those in the clinic-daytime or clinic-home differences for systolic and diastolic BP showed no significant relationship when tested by multiple regression analysis. This provides the first longitudinal evidence that clinic-daytime and clinic-home differences in BP have no substantial value in predicting the regression of target organ damage, such as left ventricular hypertrophy, that has prognostic relevance.

Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study. Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation.

OBJECTIVE: To assess whether modifications in the nighttime blood pressure fall caused by antihypertensive treatment predict the regression of end-organ damage of hypertension. METHODS: The analysis was performed in patients with essential hypertension and echocardiographically detected left ventricular hypertrophy involved in the SAMPLE study. For each patient, ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index were performed at the end of a 4-week wash-out pretreatment period, after 3 and 12 months of treatment with lisinopril or with lisinopril plus hydrochlorothiazide and after a final 4-week placebo period. For each ambulatory blood pressure monitoring the 24 h average, daytime average (0600-2400 h), night-time average (2400-0600 h) and day-night difference was computed. The percentages of dipper and non-dipper patients (i.e. the patients with night blood pressure falls greater and less than 10% of the daytime average, respectively) were also computed. RESULTS: The reproducibility of the day-night difference was low, both for comparison of the pretreatment and final placebo periods (n = 170) and for comparison of the third and the 12th month of treatment (n = 180). The reproducibility of the dipper-non-dipper dichotomy was also low, 35-40% of patients becoming non-dippers if they were dippers and vice versa, both with and without treatment The changes in left ventricular mass index after 12 months of treatment were significantly (P<0.01) related to the changes in 24 h, daytime and night-time blood pressure (r always > 0.33), but this was not the case for the treatment-induced modification of the day-night difference (r= -0.03 and -0.008 for systolic and diastolic blood pressures, respectively). CONCLUSIONS: Our results show that day-night blood pressure changes and the classification of patients into dippers and non-dippers are poorly reproducible over time. It also provides the first prospective evidence that treatment-induced changes in day-night blood pressure difference are not related to treatment-induced regression of left ventricular mass index, thus having a limited clinical significance.

Effects of lisinopril and nifedipine on the progression to overt albuminuria in IDDM patients with incipient nephropathy and normal blood pressure. The Italian Microalbuminuria Study Group in IDDM.

OBJECTIVE: Intervention trials on renal function in IDDM patients with microalbuminuria (MA) should adopt the rate of decline of glomerular filtration rate (GFR) as an outcome measure. However, normotensive IDDM patients with MA show no change in GFR over a follow-up period of 10 years. Thus, in the present study, we used the cumulative incidence of progression to albuminuria (albumin excretion rate [AER] > 200 micrograms/min) from MA as the primary endpoint and the yearly increase in AER at a rate of 50% above baseline as the secondary end-point of renal function. RESEARCH DESIGN AND METHODS: Ninety-two normotensive IDDM patients underwent double-blind, double-dummy treatment with either lisinopril or slow-release nifedipine in comparison with placebo. Ten patients discontinued the study during the 3-year follow-up period. RESULTS: During the 3-year follow-up period, 7 of 34 placebo-treated (20.6%), 2 of 32 lisinopril-treated (6.3%), and 2 of 26 nifedipine-treated (7.7%) patients progressed to clinical albuminuria (Fisher's exact test, P < 0.03). Time-to-event analysis indicated a reduction in the risk of progression to macroalbuminuria of 58.1% (95% CI 27.8-68.4%) in the 32 patients on lisinopril (P < 0.02) and of 62.5% (95% CI 32.5-73.4%) in the 26 patients on nifedipine (P < 0.02) after adjustment for mean blood pressure, glycated hemoglobin, and baseline AER in comparison with the 34 patients on placebo. Baseline AER was 71 micrograms/min (range: 20.7-187.3) in progressors and 73 micrograms/min (range: 20.2-174.1) in nonprogressors (NS). The percentage of patients who showed a > 50% yearly increase of AER above baseline values was significantly lower in the lisinopril group (13 of 32, 40.6%, P < 0.02), but not in the nifedipine group (15 of 26, 57.7%), than in the placebo group (23 of 34, 67.6%). The lisinopril group had significantly lower blood pressure values during follow-up than either the nifedipine (P < 0.05) or the placebo (P < 0.01) group. CONCLUSIONS: Our data show that both lisinopril and nifedipine are effective in delaying the occurrence of macroalbuminuria in normotensive IDDM patients with MA. As overt proteinuria strongly predicts end-stage renal failure, both treatments appear capable of preventing such a complication in normotensive IDDM patients with MA. However, lisinopril appears more powerful in slowing the course of nephropathy.

The epidemiology of resting heart rate in a male working population: association with blood pressure, age, smoking habits and other cardiovascular risk factors.

AIM: To evaluate heart rate and its relationship with some established cardiovascular risk factors in normotensive and hypertensive individuals. METHODS: We studied 881 1 men, 696 with essential hypertension and 8115 with normal blood pressure, stratified in four age groups: 20-29, 30-39, 40-49 and 50-59 years. Clinical evaluation included measures of heart rate (by pulse palpation), blood pressure (by mercury sphygmomanometer), total cholesterol, triglycerides, blood glucose and fibrinogen, and details of medical history and personal habits, with particular regard to smoking habits. RESULTS: Heart rate, which was significantly higher in hypertensive than in normotensive individuals, showed no significant change with age in the normotensive group, but a slight decline with increasing age in those with hypertension. In the normotensive group, heart rate was significantly higher in smokers than in non-smokers and ex-smokers, and showed no significant variation with increasing age, independently of smoking habits. Among those with hypertension, heart rate was not statistically different in smokers, non-smokers and ex-smokers, and showed a moderate decrease with age in non-smokers and ex-smokers, but did not change with age in smokers. CONCLUSIONS: Both ageing and smoking habits have different effects on heart rate in normotensive and hypertensive individuals.

Comparative study of acipimox and pravastatin in patients with combined hyperlipidemia.

The aim of this study was to evaluate the lipid-lowering effect of acipimox as compared to pravastatin in patients with combined hyperlipidemia. One hundred and six subjects, all males, aged 18-60 years, with total cholesterol (TC) > or = 200 mg/dl, TC/HDL-C ratio > or = 5, triglycerides (TG) > or = 200 and > or = 350 mg/dl were randomized to receive acipimox 250 mg thrice daily or pravastatin 20 mg once daily for 3 months, according to a double-blind, double-dummy design. After a 1-month wash-out period patients were crossed to the alternative regimen for further 3 months. Prior to and at the end of each treatment period, TC, LDL-C, HDL-C, TG, blood glucose, and fibrinogen were evaluated. Both acipimox and pravastatin significantly decreased TC, LDL-C, TC/HDL-C ratio and TG and increased HDL-C, without affecting plasma glucose. However, at the dosages employed in the study acipimox was more effective in reducing TG and increasing HDL-C levels, whereas pravastatin was more efficient in decreasing TC and LDL-C. There was no difference between the 2 treatments in their effects on TC/HDL-C ratio. Unlike pravastatin acipimox caused a slight but significant reduction in fibrinogen plasma levels. No serious adverse event was observed with either drug, but a major incidence of side-effects was reported during treatment with acipimox. Our findings suggest that, although both drugs at the standard dose employed in the study were effective in improving the lipid profile; in the treatment of combined hyperlipidemia acipimox might be preferable in the presence of more pronounced hypertriglyceridemia with low levels of HDL-C, whereas pravastatin might be more useful when hypercholesterolemia is predominant.

Cigarette smoking and blood pressure in a worker population: a cross-sectional study.

BACKGROUND: Cigarette smoking has been reported to cause an acute increase in blood pressure (BP). Nevertheless, many epidemiological studies have found lower average BP values in smokers than in non-smokers. The aim of this study was to evaluate the possible existence of a systematic difference in BP values between smokers and non-smokers in a worker population. METHODS: We studied 7109 employees of a metallurgical factory, all men, aged 18-60 years, 3237 non-smokers and 3872 smokers; of the latter, 816 smoked less than 10 cigarettes per day (light smokers), the others smoked 10 or more cigarettes per day. Clinical examination included measures of resting BP (by mercury sphygmomanometer), heart rate (HR) (by pulse palpation), body weight and height. Data were adjusted for age and body mass index (BMI). Four age groups (18-30, >30, >40 and >50 years) and 3 BMI groups (< 25, 25-30, >30) were considered. RESULTS: In smokers, the adjusted values of systolic BP (SBP) and HR (127.72 mmHg and 75.16 beats/min, respectively) were slightly but significantly higher than in non-smokers (127.1 mmHg, P < 0.05 and 72.64 beats/min, P < 0.001), whereas diastolic BP (DBP) was significantly lower (83.37 versus 84.31 mmHg, P < 0.001). Considering the amount of cigarettes smoked, the mean BP values of light smokers were not significantly different from those of subjects smoking 10 or more cigarettes per day, whereas HR mean values were significantly higher in the latter. The prevalence of hypertension (WHO criteria) was similar in smokers and non-smokers in each age group. CONCLUSIONS: Our data showed slightly but statistically higher SBP and HR, and lower DBP mean values in smokers than in non-smokers; however, the differences in BP, although significant from the statistical point of view, were not of actual clinical significance.

Evaluation of nocturnal blood pressure by the Multi-P Analysis of 24-hour ambulatory monitoring.

Ambulatory blood pressure monitoring (ABPM) is utilized to identify "dippers" and "non dippers" among hypertensives. Such a classification has either prognostic or therapeutical implications. Rigid definitions of nocturnal time period (e.g., from 10 p.m. to 7 a.m.) may not correspond to actual sleep patterns, and thus may lead to faulty interpretations. In our study, we analyzed 32 ABPM; diurnal and nocturnal blood pressure (BP) were assessed by three different ways: the patients' diary method; fixed intervals utilized by Spacelabs software; Multi-P Analysis (MPA) of the data. MPA method proved to be effective to evaluate nocturnal BP values. In comparison with Spacelabs program, it seems to define more precisely nocturnal BP, which differs less from the real sleep-time values. This modifies the percentage of dippers, which is greater than that obtained by Spacelabs program and equal to that calculated by the patients reported nocturnal sleep intervals. These results suggest that MPA method may be a contribution to a better definition of nocturnal BP.

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.

Associations between plasma fibrinogen levels and cardiovascular risk factors in hypertensive men.

BACKGROUND: Fibrinogen levels are reported to be elevated in hypertensive patients and tend to cluster with nearly all other established cardiovascular risk factors. The aim of this study was to evaluate the relationship between plasma fibrinogen and a number of other cardiovascular risk factors in patients with essential hypertension. METHODS: We studied 118 men with essential hypertension, aged 18-65 years. The clinical evaluation included measurements of blood pressure (mercury sphygmomanometer, Korotkoff I and V), levels of plasma fibrinogen, total cholesterol, high-density-lipoprotein (HDL) cholesterol, triglycerides and blood glucose and the ratio of total-cholesterol to HDL-cholesterol levels; a detailed history of medical and personal habits was also recorded. RESULTS: As expected, plasma fibrinogen levels were significantly higher in smokers than in non-smokers, with the number of cigarettes smoked correlating positively with the fibrinogen level. Patients with a total-cholesterol level in excess of 220 mg/dl had significantly higher fibrinogen levels, and both univariate and multivariate analyses showed total-cholesterol and fibrinogen levels to be positively correlated. A weaker but significant relationship was noted between the fibrinogen level and triglyceride levels (P = 0.0017) and between the fibrinogen level and the ratio of total-cholesterol to HDL-cholesterol levels (P = 0.0006). Fibrinogen levels were not significantly associated with either systolic or diastolic blood pressures. CONCLUSION: A family history of hypertension appears to potentiate the tendency of fibrinogen to cluster with other cardiovascular risk factors in hypertensive patients.

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.

Occupational noise exposure and blood pressure.

OBJECTIVE: To investigate the relationship between occupational noise exposure and blood pressure. METHODS: We studied 8811 workers at a metallurgical factory, who were exposed to different levels of noise at the worksite: < or = 80 dB for 8078 workers and > 80 dB for 733 workers. A clinical examination, including measurements of blood pressure (by mercury sphygmomanometer, Korotkoff phases I and V), heart rate (by pulse palpation), body weight and height, was performed. The subjects were stratified into four age groups (18-30, 31-40, 41-50 and > 50 years) and into two body mass index groups: normal weight (< or = 25 kg/m2) and overweight (> 25 kg/m2). In order to eliminate possible confounding factors and statistical bias, a retrospective case versus control analysis was also carried out. RESULTS: The epidemiologic approach showed that the systolic blood pressure (SBP) but neither the diastolic blood pressure (DBP) nor the heart rate values were statistically higher in the group who were exposed to noise levels of > 80 dB, although the difference could be considered clinically relevant only in the older age group. The prevalence of hypertension (according to World Health Organization criteria) was higher among the workers who were exposed to the higher levels of noise. Stratification for body mass index confirmed the existence of a higher prevalence of hypertension in the exposed group. The results from the case versus control analysis indicated that both the SBP and the DBP levels in the exposed group were significantly higher than those in the reference group, and confirmed the existence of a higher prevalence of hypertension in the exposed group. CONCLUSIONS: The present data suggest that occupational exposure to noise levels exceeding 80 dB may lead to a higher prevalence of hypertension and to increased blood pressure values, although the results appear quantitatively different according to the approach that is taken to the problem (i.e. the epidemiologic or the case versus control approach).

Profile of in vitro binding affinities of neuroleptics at different rat brain receptors: cluster analysis comparison with pharmacological and clinical profiles.

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.

Differential antagonism of denzimol to various components of metrazol-induced seizures in rats and mice.

The antagonism of various components of maximal metrazol-seizures and the induction of ataxia have been studied in mice and rats by comparing Denzimol to 10 standard antiepileptic drugs. The data were analyzed by Cluster and Principal Components Analysis. Denzimol, phenytoin, carbamazepine and AD-810 showed an antagonistic effect on tonic but not on clonic seizures regardless of the animal species. Barbiturates, benzodiazepines and valproic acid, on the other hand, antagonized the whole pattern of metrazol-seizures. The selective activity of Denzimol and phenytoin against tonic seizures was also confirmed from literature data, which reported the activity of these compounds against bicuculline, thiosemicarbazide or picrotoxin induced convulsions.