Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study.

AIMS: As melatonin has been found to play a role in the mechanisms of cardiovascular regulation, we designed the present study to evaluate whether the evening ingestion of the pineal hormone might interfere with the antihypertensive therapy in hypertensive patients well-controlled by nifedipine monotherapy. METHODS: Forty-seven mild to moderate essential hypertensive outpatients taking nifedipine GITS 30 or 60 mg monotherapy at 08.30 h for at least 3 months, were given placebo or melatonin 5 mg at 22.30 h for 4 weeks according to a double-blind cross-over study. At the end of each treatment period patients underwent a 24 h noninvasive ambulatory blood pressure monitoring (ABPM) during usual working days; sleeping period was scheduled to last from 23.00 to 07.00 h. RESULTS: The evening administration of melatonin induced an increase of blood pressure and heart rate throughout the 24 h period (DeltaSBP = + 6.5 mmHg, P < 0.001; DeltaDBP = + 4.9 mmHg, P < 0.01; DeltaHR = + 3.9 beats min-1, P < 0.01). The DBP as well as the HR increase were particularly evident during the morning and the afternoon hours. CONCLUSIONS: We hypothesize that competition between melatonin and nifedipine, is able to impair the antihypertensive efficacy of the calcium channel blocker. This suggests caution in uncontrolled use of melatonin in hypertensive patients. As the pineal hormone might interfere with calcium channel blocker therapy, it cannot be considered simply a dietary supplement.

Effect of low-dose manidipine on ambulatory blood pressure in very elderly hypertensives.

To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure (BP) and heart rate (HR) in very elderly hypertensive patients, 54 patients aged 76-89 years (mean age 81.8 years) with systolic blood pressure (SBP) > 160 mmHg and diastolic blood pressure (DBP) > 90 mmHg were studied. After a 4-week placebo washout period, patients were randomized to receive manidipine 10 mg or placebo, both administered once daily for 8 weeks. Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter. At each visit casual BP and HR were measured. At the end of the placebo period and after 8 weeks of active treatment, noninvasive 24-hour ambulatory blood pressure measurement (ABPM) was performed. Manidipine significantly lowered casual sitting and standing SBP (P < 0.001) and DBP (P < 0.001) at the trough level. ABPM showed a significant decrease in 24-hour SBP and DBP values (P < 0.001), daytime SBP and DBP (P < 0.001), and night-time SBP (P < 0.001) and DBP (P < 0.005). In addition, ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval, without effect on the circadian BP profile. The trough/peak ratio was 0.67 for SBP and 0.59 DBP. No statistically significant change in HR was observed. The treatment was well tolerated, and there were no serious side effects. In conclusion, in very elderly hypertensive patients, once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP.

Beta-blocker effects on plasma lipids during prolonged treatment of hypertensive patients with hypercholesterolemia.

The aim of this study was to compare the effects of long-term monotherapy with four different beta-blockers on plasma lipids in hypercholesterolemic hypertensive patients. We studied 152 subjects with essential hypertension [diastolic blood pressure (DBP) >90 mm Hg], total cholesterol (TC) >240 and <330 mg/dl, and triglycerides (TGs) <300 mg/dl. After a 4-week washout period with placebo, patients were randomized to receive propranolol, 160 mg/day (n = 37), atenolol, 100 mg/day (n = 38), bisoprolol, 10 mg/day (n = 39), or celiprolol, 400 mg/day (n = 38), for 18 months. No cholesterol-reducing drug was allowed. Blood samples for evaluation of TC, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol (HDL-C), and TGs were taken before and after the placebo period and subsequently every 6 months. No beta-blocker worsened TC or LDL-C. Nonselective propranolol caused the most pronounced changes in HDL-C and TGs. Beta1-Selective atenolol produced the same qualitative effects, but to a lesser extent. The more beta1-selective bisoprolol did not affect HDL-C and TGs. Celiprolol significantly improved the lipid profile by significantly decreasing TC, LDL-C, and TGs, and increasing HDL-C. These findings suggest that in hypercholesterolemic hypertensive patients, (a) beta1-selective beta-blockers are likely to adversely affect plasma lipids to a lesser extent than nonselective ones; and (b) celiprolol is able to improve the lipid pattern, which could be because of its peculiar ancillary properties.

Effects of insufficient sleep on blood pressure in hypertensive patients: a 24-h study.

The influence of acute sleep deprivation during the first part of the night on 24-h blood pressure monitoring (ABPM) was studied in 36 never-treated mild to moderate hypertensive patients. According to a crossover design, they were randomized to have either sleep deprivation or a full night's sleep 1 week apart, during which they were monitored with ABPM. Urine samples for analysis of nocturnal urinary excretion of norepinephrine were collected. During the sleep-deprivation day, both mean 24-h blood pressure and mean 24-h heart rate were higher in comparison with those recorded during the routine workday, the difference being more pronounced during the nighttime (P < .01). Urinary excretion of norepinephrine showed a significant increase at night during sleep deprivation (P < .05). Blood pressure and heart rate significantly increased in the morning after a sleep-insufficient night (P < .05). These data suggest that lack of sleep in hypertensive patients may increase sympathetic nervous activity during the night and the following morning, leading to increased blood pressure and heart rate. This situation might represent an increased risk for both target organ damage and acute cardiovascular diseases.

Long-term effects of ramipril and nitrendipine on albuminuria in hypertensive patients with type II diabetes and impaired renal function.

The aim of this study was to compare the effects of ramipril and nitrendipine chronic treatment on urinary albumin excretion (UAE) in hypertensive patients with type II non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal function. A 2-year, prospective, randomised study was conducted on 51 men with a diastolic blood pressure (DBP) > or =95 and < or =105 mm Hg, stable NIDDM, serum creatinine between 1.6 and 3.0 mg/dl and persistent UAE >300 and <2000 mg/24 h. After a 3-month preliminary observation period, during which patients began a low-protein, low-sodium diet, and a subsequent 4-week run-in period on placebo, patients were randomly treated with ramipril 5 mg or nitrendipine 20 mg for 2 years. Both drugs similarly reduced BP without affecting glucose homeostasis. In the ramipril group UAE significantly decreased after only 3 months of treatment, whereas in the nitrendipine group a significant although lesser reduction in UAE was observed only after 1 year. During the second year the UAE% change was not statistically different between the two treatments. Serum creatinine and creatinine clearance showed no significant change with both drugs. The progression of renal insufficiency as assessed by the rate of reduction of creatinine clearance over the 2 years of the study was similar in the ramipril and the nitrendipine groups. In conclusion both ramipril and nitrendipine were associated with a decrease in UAE although such a reduction was earlier and more marked with ramipril. The decline of renal function did not differ significantly between the two treatments.

Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertensive patients.

AIMS: The aim of this study was to compare the effects of the ACE-inhibitor lisinopril and the angiotensin II receptor antagonist losartan on insulin sensitivity in the treatment of non diabetic hypertensives. METHODS: Twenty-five non diabetic subjects with mild to moderate hypertension, 11 females and 14 males, aged 44-63 years, after a 4-week wash-out period on placebo, were randomized to receive lisinopril 20 mg once daily or losartan 50 mg once daily for 6 weeks. Following another 4-week wash-out period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the active treatment periods, blood pressure (BP) was measured (by standard mercury sphygmomanometer, Korotkoff I and V) and insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. RESULTS: Both lisinopril and losartan significantly reduced SBP (by a mean of 20.2 and 17.2 mmHg, respectively) and DBP (by a mean of 15.2 and 12.3 mmHg, respectively), with no difference between the two treatments. GIR, used as an indicator of insulin sensitivity, was significantly increased by lisinopril (+1.5 mg min(-1) kg(-1), P<0.05 vs baseline) but not by losartan (+0.42 mg min(-1) kig(-1), NS), the difference between the two drugs being statistically significant (P<0.05). TGR was increased by lisinopril (+7.3 g, P<0.05 vs baseline), whereas losartan did not significantly modify it (+1.9 g, NS). CONCLUSIONS: In conclusion, with all cautions due to an absence in this study of a randomized placebo phase, our findings suggest that lisinopril improved insulin sensitivity whereas losartan did not affect it.

Sexual function in hypertensive males treated with lisinopril or atenolol: a cross-over study.

To evaluate the effect of antihypertensive treatment on sexual activity, 90 hypertensive men, aged 40 to 49 years, all married and without history of sexual dysfunction were treated with 100 mg of atenolol or 20 mg of lisinopril for 16 weeks, according to a double-blind, randomized, cross-over design. During the first month of therapy, sexual activity, assessed as number of sexual intercourse episodes per month, significantly declined with both atenolol (from 7.8 +/- 4.3 to 4.5 +/- 2.8, P < .01 v placebo) and lisinopril (from 7.1 +/- 4.0 to 5.0 +/- 2.5, P < .05 v placebo). Ongoing with the treatment, sexual activity tended toward recovery in the lisinopril (7.7 +/- 4.0 sexual intercourse episodes per month, P = NS v placebo), but not in the atenolol group (4.2 +/- 2.8, P < .01 v placebo), with a statistically significant difference between the two drugs (P < .01). The percentage of patients who complained of sexual dysfunction symptoms was significantly higher in the atenolol- than in the lisinopril-treated group (17% v 3%, P < .05). These findings suggest that atenolol induces a chronic worsening of sexual activity, whereas lisinopril causes only a temporary decline.

ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients.

The aim of this study was to compare the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on insulin sensitivity and plasma fibrinogen in overweight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were randomized to perindopril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then, after a new placebo period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the treatment periods, blood pressure was measured, plasma fibrinogen was evaluated, and insulin sensitivity was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. Both perindopril and losartan reduced SBP (by a mean of 20.2 mm Hg, p < 0.001 vs. placebo; and 15.8 mm Hg, p = 0.002 vs. placebo, respectively) and DBP (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8 mm Hg, p = 0.01 vs. placebo respectively), with no difference between the two treatments. GIR was significantly increased by perindopril (+2.91 mg/min/kg, p = 0.042 vs. placebo), but not by losartan (+0.28 mg/min/kg, NS). TGR was not modified by losartan but was increased by perindopril (+9.3 g, p = 0.042 vs. placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p = 0.022 vs. placebo) but not by losartan (-16.8 mg/dl, NS). The perindopril-induced decrease in fibrinogen was correlated with the increase in GIR (r = 0.39; p < 0.01). These findings suggest that fibrinogen decrease produced by the ACE inhibitor is related to its action on insulin sensitivity, which seems to be dependent not on angiotensin II blockade but rather on other mechanisms.

Fixed combination of benazepril and low-dose amlodipine in the treatment of mild to moderate essential hypertension: evaluation by 24-hour noninvasive ambulatory blood pressure monitoring.

The antihypertensive efficacy and tolerability of a fixed combination of benazepril (10 mg) and low-dose amlodipine (2.5 mg) were assessed in 24 patients (mean age, 43.9 years) with uncomplicated mild to moderate essential hypertension [supine diastolic blood pressure (DBP) > or = 95 and < or = 120 mm Hg)]. After 2 weeks of washout taking placebo, patients were randomized to receive the fixed combination or placebo, both administered once daily for 3 weeks, according to a double-blind, crossover design. Patients were checked at the end of the washout period and every 3 weeks thereafter. At each visit, 24-h ambulatory BP monitoring (ABPM) was performed by a noninvasive device (Spacelabs 90207); casual BP (by mercury sphygmomanometer), heart rate (HR), and body weight also were measured. The fixed combination significantly reduced systolic (SBP) and DBP values throughout the 24 h as compared with placebo, without affecting the normal BP circadian variability. The antihypertensive effect of the fixed combination could be observed to a similar extent during the day and night and was still significant 24 h after dosing. HR and body weight were not affected by the treatment. The fixed combination of benazepril 10 mg/amlodipine 2.5 mg was well tolerated, and no patient withdrew from the study because of side effects.

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.

Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects.

OBJECTIVE: To determine whether the evening intake of 5 mg melatonin affects 24 h arterial blood pressure and heart-rate profiles. METHODS: Twenty-one young normotensive subjects were administered placebo or melatonin for 4 weeks, according to a cross-over double-blind design, and were subjected to ambulatory blood pressure monitoring on the first and last days of each treatment period. RESULTS: The chronic melatonin intake caused a decrease in systolic blood pressure throughout the 24 h period (109.1+/- 7.2 versus 113.6 +/- 8.15 mmHg, P < 0.05), a decrease in diastolic blood pressure (by 6.4 mmHg, P < 0.05) limited to the second half of the night, a slight lowering of the heart rate during the diurnal hours (78.6 +/- 7.6 versus 81.5 +/- 10.1 beats/min, P < 0.05) and an acceleration of a similar degree during the second half of the night. The slight hypotensive action and the diurnal heart-rate lowering may be explained theoretically in terms of various complex and synergistic mechanisms that so far have been verified only in experimental studies on animals. The etiology of the nocturnal heart-rate acceleration remains unknoiwn. Further controlled studies are needed in order to better understand the cardiovascular effects of melatonin and to evaluate possible pharmacologic interactions. CONCLUSION:

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.

Effect of a westward transmeridian flight on ambulatory blood pressure monitoring in normotensive subjects.

OBJECTIVE: To evaluate the effects of a westward transmeridian flight over six time zones (from Milan to New York) on ambulatory blood pressure monitoring (ABPM) in normotensive individuals. METHODS: Eighteen normotensive subjects (blood pressure < 140/90 mmHg), 11 men and seven women, of mean age 38.3 years, were studied. On the day of travel they underwent 26 h noninvasive ABPM (started at 1100 h); the take-off time was 1200 h and the landing time was 8 h later, at 1400 h New York time (2000 h Italian time). Subjects were requested not to sleep until 2300 h and to get up at 0700 h the following morning. The results were compared with those of a 26 h ABPM performed in Italy the week before during which they slept from 2300 h to 0700 h. RESULTS: During the flight blood pressure and heart rate did not change compared with values during the corresponding time interval of the control day. After the landing, during the New York afternoon and evening (corresponding to the Italian sleeping time), blood pressure and heart rate remained unchanged, whereas during the night they decreased significantly, although their drop was less pronounced than that during the control day. CONCLUSION: The results of this study indicate that the decrease in blood pressure during sleep is the result of sleep itself rather than of the actual time of day.

Comparative effects of nebivolol and atenolol on blood pressure and insulin sensitivity in hypertensive subjects with type II diabetes.

The aim of this double-blind, parallel group study was to compare the effects of nebivolol and atenolol on blood pressure (BP) and insulin sensitivity in hypertensive patients with type II, non-insulin dependent diabetes mellitus (NIDDM). After a 4-week run-in period on placebo, 30 patients (14 males and 16 females) aged 43 to 69 years, with stable NIDDM and mild to moderate hypertension (DBP > or =95 and <116 mm Hg) were randomised to receive either nebivolol 5 mg or atenolol 50 mg, both administered once daily for 6 months. At the end of the placebo and the active treatment periods, supine and standing BP was measured, 24-h urinary C-peptide, HbA1c, plasma glucose and lipid levels were evaluated and an euglycaemic hyperinsulinaemic clamp was performed to evaluate insulin sensitivity: glucose infusion rate during the last 60 min of clamp and total glucose requirements were evaluated. Nebivolol 5 mg once daily was of an equivalent efficacy as atenolol 50 mg once daily at reducing supine and standing systolic and diastolic BP values. Neither beta-blocker adversely affected carbohydrate metabolism in terms of insulin sensitivity, whole body glucose utilization, HbA1c and 24-h urinary C-peptide excretion. No significant changes in cholesterol (total, high density and low density lipoprotein) and triglycerides plasma levels were observed with both beta-blockers. These findings indicate that, in hypertensive patients with NIDDM, ie, in subjects who have established insulin resistance, treatment with nebivolol and atenolol neither further deteriorated insulin sensitivity nor adversely affected the lipid profile.

Making sense of it: a neuro-interactional model of meaning emergence in critically ill ventilated patients.

Emphasis on meaning underpins a current thrust of knowledge development in nursing, especially in the client domain. Examination of meaning in the interactional context and through varying levels of consciousness has not been examined. Initially, an integrated model was developed deductively from philosophical, theoretical and research-oriented sources. This model was meant as a guide to begin examining how patients with varying levels of consciousness make sense of their intensive care unit experience. Over a 10-month period of fieldwork, this author observed patients twice daily through their intensive care unit stay to capture the nature and content of thinking processes. The resulting neuro-interactional model describes patients' thinking processes and scope of meaning as a function of levels of consciousness as well as factors which affect thinking and meaning. Theory, research and practice implications are presented.

Effects of a restricted sleep regimen on ambulatory blood pressure monitoring in normotensive subjects.

The influence of sleep deprivation during the first part of the night on 24-h ambulatory blood pressure monitoring (ABPM) was studied in 18 normotensive subjects. They underwent two ABPM, one week apart: during the first, they slept from 11 PM to 7 AM, and during the second, from 2 AM to 7 AM. The main differences were observed at dawn, before awakening, when SBP and DBP significantly decreased (P < .01) in the restricted sleep regimen, and during the morning after the recovery sleep, when SBP and HR significantly increased (P < .05). The explanation for these findings is not obvious. We suppose that the decrease in SBP and DBP at dawn might be due to a reorganization of the sleep phases in the restricted sleep regimen, whereas the increase in SBP and HR after awakening might be due to a greater sympathetic activation, as though sleep deprivation was a stressful condition.

Repeated office blood pressure controls reduce the prevalence of white-coat hypertension and detect a group of white-coat normotensive patients.

BACKGROUND: The aim of this study was to evaluate whether repeated office blood pressure controls may change the prevalence of white-coat hypertension among hypertensive patients. METHODS: We studied 221 newly diagnosed, never-treated hypertensive patients, all men, aged 31-60 years. On the first visit, they underwent sitting blood pressure measurements (two readings were taken by mercury sphygmomanometer and averaged) and non-invasive 24 h ambulatory blood pressure monitoring (ABPM) every 15 min. Thereafter, each patient made four further visits over an 8-week period. On each visit, three sitting readings were taken and averaged. On the last visit, ABPM was performed again. Subjects who had hypertension in the clinic but whose daytime ambulatory blood pressure was less than 134/90 mmHg were considered to have white-coat hypertension. RESULTS: On the first visit, all patients were, by definition, clinically hypertensive and ABPM detected a prevalence of white-coat hypertension of 25.8%. On the following visits, the prevalence of clinical hypertensive patients progressively declined; on the last visit, the 82.3% of all patients resulted yet clinical hypertensive: on ambulatory blood pressure 71.9% were sustained hypertensives, whereas 10.4 had white-coat hypertension. Of the patients originally labelled as hypertensive, 17.7% proved to be clinically normotensive: 13.6% had also daytime ambulatory blood pressure in the normal range, whereas 4.1% showed elevated blood pressure during daytime ABPM (white-coat normotensives). CONCLUSION: These data suggest that repeated office blood pressure controls in newly diagnosed hypertensives reduce the number of office hypertensive patients, reduce the number of white-coat hypertensive patients and detect a small group of white-coat normotensive patients.

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 by 24-hour ambulatory blood pressure monitoring of efficacy of manidipine hydrochloride 10, 20 or 40 mg once daily as compared to placebo in treating mild to moderate essential hypertension: a double-blind, randomized, parallel group, placebo-controlled study.

In a double-blind, randomized, placebo-controlled, parallel-group study the ambulatory blood pressure monitoring (ABPM) and relative tolerability of different doses of manidipine hydrochloride (10, 20 and 40 mg) were compared to placebo in patients with mild to moderate essential hypertension. After an initial 2-week run-in period on placebo, 52 patients, 32 males and 20 females, aged 40 to 63 years, were randomized to receive manidipine 10 mg, 20 mg, 40 mg or placebo, all administered once daily for 4 weeks. Patients were checked after the initial placebo phase and every 2 weeks thereafter. At each visit, casual BP and HR were measured. At the end of the placebo period and after 4 weeks of active treatment, non-invasive 24-h ABPM was performed. 24-h, day-time and night-time ambulatory BP as well as the area under the curve (AUC) and casual BP were dose-dependently reduced by manidipine 10, 20 and 40 mg, without changes in the normal BP circadian profile. The trough:peak ratio for both SBP and DBP was higher than 50% for all three manidipine dosage regimens. The percentage of abnormal ambulatory SBP and DBP readings was significantly reduced in all manidipine-treated groups versus placebo. The risk/benefit ratio suggests that the intermediate manidipine dosage (20 mg) could be a suitable dose regimen for the majority of patients with mild to moderate hypertension.

Efficacy and tolerability of manidipine hydrochloride in the long-term treatment of mild-moderate hypertension. Manidipine Efficacy in Long-Term Treatment Group.

The aim of this multicenter study was to evaluate the efficacy and tolerability of manidipine hydrochloride, a new calcium-antagonist of the dihydropyridine group, in the long-term treatment of mild to moderate hypertension. After a 2-week run-in period on placebo, 183 patients, 98 males and 85 females, with mean age of 53.8 years, sitting DBP > or = 95 and < or = 115 mmHg and SBP < or = 210 mmHg, were given manidipine 10 mg once daily. Two weeks later, patients whose DBP was > or = 90 mmHg or with a reduction in DBP < 10 mmHg were administered with manidipine 20 mg once daily. Follow-up visits were performed at 6, 10, 14, 26, 38 and 52 weeks after starting manidipine treatment. All BP (by mercury sphygmomanometer, Korotkoff I and V) and heart rate (HR) measures were made 24 h after dosing. Adverse events and laboratory data were recorded. Particular attention was paid to the collection of possible major cardiovascular (angina pectoris, myocardial infarction) and cerebrovascular (IRA, stroke) events, observed during the treatment period. One-hundred-and-fifty-one patients completed the study (79 on a 10 mg dose and 72 on a 20 mg dose), whereas 32 dropped out (11 lost to follow-up, 11 insufficient therapeutic response, 7 ADRs, 3 other causes). Significant reductions of BP values were achieved during the manidipine 10 mg treatment period. Analysis of covariance between doses confirmed a more potent hypotensive effect of manidipine 20 mg as compared to 10 mg on sitting DBP and mean BP and on standing SBP, especially in patients with moderate hypertension. At the end of 1 year of treatment the success rates (defined as sitting DBP > or = 90 mmHg or a reduction of > or = 10 mmHg vs baseline) were similar in the two groups (manidipine 10 mg: 96.1%; manidipine 20 mg: 94.5%). No clinically relevant change in HR was observed. Overall, 28 patients (17 in the manidipine 20 mg and 11 in the manidipine 10 mg treated group) complained of adverse events, the most common being ankle oedema (4.9%), headache (3.8%), palpitation (2.7%) and flushing (2.2%). Neither cardiovascular nor cerebrovascular events or other serious adverse event were reported. In conclusion, a significant and constant reduction of BP values was observed with long-term treatment with manidipine. The reduction in BP was dose-related especially in patients suffering from moderate hypertension. Adverse events were mild and relatively more frequent with the higher manidipine dosage.