Franco Tettamanti

Comparative effects of celiprolol, propranolol, oxprenolol, and atenolol on respiratory function in hypertensive patients with chronic obstructive lung disease

SummaryThe aim of the study was to compare the pulmonary effects of four beta-blockers with different ancillary properties: propranolol (non-beta1 selective without ISA), oxprenolol (non-beta1 selective with ISA), atenolol (beta1 selective), and celipropol (beta1 selective with mild beta2-agonist and alpha2-antagonist activity) in hypertensive patients with chronic obstructive lung disease. Ten asthmatic patients, all males, aged 50–66 years were studied. Entry criteria were a) DBP≧95 mmHg and ≦115 mmHg; b) FEV1<70% of the theoretical values; c) FEV1 increase of at least 20% after salbutamol inhalation (200 μg). After a 2-week washout period on placebo, each patient received propranolol (80 mg/day), oxprenolol (80 mg/day), atenolol (100 mg/day), and celiprolol (200 mg/day) for 1 week, according to a randomized, cross-over design. At the end of the washout and of each treatment period, airway function, assessed by FEV1, FVC, and FEV1%, was evaluated by spirometry both in the basal condition and after salbutamol inhalation. Unlike propranolol and oxprenolol, which significantly reduced FEV1 and inhibited the bronchdilator response to inhaled salbutamol, atenolol and celiprolol did not significantly affect respiratory function and did not antagonize salbutamol effects. Celiprolol more closely approached placebo in its respiratory effects than did atenolol, although the differences were not statistically significant.

Plasma lipids during chronic antihypertensive therapy with different β-blockers

The aim of this study was to compare the effects of long-term monotherapy with five different beta-blockers on plasma lipids in patients with essential hypertension. We studied 99 male patients, aged 35-55 years, with mild to moderate hypertension, who worked in the same community. After a 1-month placebo period, patients were assigned to receive propranolol (160 mg/day), atenolol (100 mg/day), bisoprolol (10 mg/day), mepindolol (10 mg/day), or celiprolol (400 mg/day). Therapy was continued for 2 years. Blood pressure (BP), heart rate, and blood samples for evaluation of total cholesterol (TC), LDL-cholesterol (LDL-C), triglycerides (TG) and HDL-cholesterol (HDL-C) were taken before and after the initial placebo period, and subsequently every 6 months from the beginning of active treatment. All beta-blockers caused similar reductions in BP that were maintained throughout the study. None of the beta-blockers significantly affected TC or LDL-C. Propranolol, a nonselective beta-blocker, caused the most pronounced changes in TG (+33 to 43%) and in HDL-C (-30 to -32%). Atenolol, a beta 1-selective agent, had the same quantitative effects, but to a lesser extent (TG + 23 to 30%; HDL-C -15 to -19%). Bisoprolol, more beta 1-selective than atenolol, and mepindolol, nonselective with ISA, increased TG (+20 to 28% and +14 to 25%, respectively) but did not significantly affect HDL-C. In contrast, celiprolol, a highly cardioselective beta-blocker with beta 2-partial agonism, improved lipid risk factors by significantly reducing TG (-14 to -21%) and increasing HDL-C (+8 to 14%).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring

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)

Left ventricular anatomy and function in normotensive young adults with hypertensive parents Study at rest and during handgrip

Using digitized M-mode echocardiograms, we evaluated left ventricular (LV) anatomy and function at rest and during handgrip in 24 normotensive young adults with both parents hypertensive (HP+), each matched for age, sex, body weight, and body surface area with one normotensive adult with both parents normotensive (HP-). LV parameters were within the normal range in all HP+ and HP-. At rest, HP+ as compared to HP- had higher systolic and diastolic blood pressure (BP), septal and posterior wall thickness, and LV mass; LV diastolic diameter and end-systolic wall stress were similar in the two groups. Modified midwall fractional shortening, peak shortening rate of LV diameter and peak thickening rate of LV posterior wall, indices of LV systolic function, and peak lengthening rate of LV diameter and peak thinning rate of LV posterior wall, indices of ventricular relaxation, were significantly higher in HP+. Handgrip induced significant (P < .001) and percent-comparable increases of systolic and diastolic BP, heart rate, and cardiac output in HP+ and HP-; peak shortening and lengthening rates of LV diameter and peak thickening and thinning rates of LV posterior wall increased significantly in HP-, whereas in HP+ the value of the four parameters, higher at rest as compared to HP-, did not show any further increase. In conclusion, normotensive young adults with high genetic risk for hypertension have higher BP and thicker and overactive LV as compared to subjects with normotensive parents. Handgrip stimulates LV function in offspring of normotensives, but not the already hyperkinetic LV of hypertensive offspring.

The effect of celiprolol on the blood lipid profile in hypertensive patients with high cholesterol levels

SummaryThe aim of this study was to compare the effects of chronic antihypertensive therapy with either celiprolol or atenolol on plasma lipids in patients with hypercholesterolemia. Forty-six patients with essential hypertension and a total cholesterol (TC) concentration > 220 mg/dl were studied. After 1 month on placebo, patients were stratified into five classes on the basis of their plasma TC levels and then randomized to receive atenolol 100 mg/day or celiprolol 400 mg/day for 1 year. Blood pressure (BP), heart rate (HR), and blood samples for evaluation of TC, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglycerides (TG) were taken before and after the placebo period, and every 6 months from the beginning of the active treatment. Celiprolol and atenolol caused similar reduction in BP. Both atenolol and celiprolol decreased TC. Atenolol significantly reduced HDL-C, while celiprolol increased it (p<0.01 at 12 months), and the difference between the two drugs was statistically significant in this regard. LDL-C levels were not significantly affected by atenolol, but were progressively reduced by celiprolol (p<0.05 at 6 months, p<0.01 at 12 months). TG rose under atenolol but was reduced by celiprolol (p<0.05). The results of this study show that the celiprolol-induced changes in plasma lipids may be favorable and suggest that, in hypertensive patients with high cholesterol levels, beta-blocker therapy with celiprolol may be effective in lowering BP without worsening the lipid profile.

β-blocker effects on plasma lipids in antihypertensive therapy : importance of the duration of treatment and the lipid status before treatment

The aim of this study was to evaluate the effects of long-term monotherapy with four β-blockers provided with different pharmacological properties on plasma lipids in both normocholesterolemic and hypercholesterolemic hypertensive patients. After a 1-month run-in period on placebo. 70 hypertensive patients with basal total cholesterol (TC) 220 mg/dl were treated for 3 years with propranolol 160 mg/day or atenolol 100 mg/day or bisoprolol 10 mg/day or mepindolol 10 mg/day, while 59 hypertensive patients with basal TC > 220 mg/dl were given the same β-blockers at the same dosage for 6 months. In both normocholesterolemic and hypercholesterolemic hypertensive patients. HDL-C and triglyceride (TG) levels showed significant changes that appeared to be related to the type of β-blocker used and to the duration of therapy. Nonselective, non-ISA (intrinsic sympathomimetic activity) propranolol caused the most pronounced changes, decreasing HDL-C and increasing TG concentrations; β1-selective atenolol and bisoprolol had similar, but less remarkable effects; even more discrete changes were observed on mepindolol (with ISA). The variations in HDL-C and TG values reached their peak in 6–12 months of β-blocker therapy; then, after a plateau phase, they showed a progressive trend toward pretreatment levels. In hypercholesterolemic patients, the percent change in both HDL-C and TG values was lower compared to normocholesterolemic 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 Organizations 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.

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.

Community control of hypertension at the worksite in a metallurgical factory: Results of 1-year follow-up

This study was designed to assess advantages and cost-effectiveness of community control of hypertension at the worksite in a metallurgical factory in Pavia. Under consent of managers and trade-unionists, a screening program was undertaken. 2701 subjects (95% of the total number of employees) were screened: 277 (10.2%) were hypertensive, 101 (38%) did not know to be hypertensive, 56 (22%) knew to be hypertensive but they were untreated and only 20 (8%) of those under treatment were adequately treated. Of the 277 essential hypertensives, 262 (94%) adhered to the program. They were assigned to beta-blocking or diuretic treatment following WHO rules. Then an aggressive follow-up was started (the hypertensives were periodically called to control at the worksite). 257 (98%) were partecipants 1 year later. Our worksite hypertension control program allowed us to identify many cases of undiagnosed or untreated hypertension and to start an early treatment. One year after entry, the percentage of hypertensives achieving a normal blood pressure (85%) was almost twice as that obtained by conventional clinical approach employing the same type of treatment. Besides, more than 95% of hypertensives remained under control at 1 year. Regarding the costs, it is difficult to generalize, but our study suggests that, if there is the will, it is possible to realize programs of hypertension community control at a very low cost (in our experience: 43 dollars per hypertensive per year).

Effects of celiprolol on cardiovascular responses to smoking in normotensive smokers

Dear Sir, Cigarette smoking is a major risk factor for cardiovascular disease and doubles the risk of myocardial infarction, sudden death, and stroke in patients with hypertension [1]. The mechanisms by which smoking might contribute to the development of cardiovascular complications include an acute increase in heart rate (HR), blood pressure (BP), cardiac contractility, and myocardial oxygen demand, primarily mediated by nicotine-induced activation of the sympathetic nervous system [2,3]. Previous studies have reported that beta-blocking agents attenuate the acute tachycardia induced by cigarette smoking but have little effect on the BP increase [4-9]. Furthermore, such drugs have been shown to enhance the vasoconstrictor effect of smoking on the systemic and coronary circulation, presumably due to the unopposed c~-adrenergic receptor stimulation [4-6, 10]. We recently evaluated the influence of acute oral administration of celiprolol, a new ~rselective antagonist with ~2agonist and mild a2-adrenergic blocking properties [11,12], on cardiovascular effects of cigarette smoking in normotensive smokers. Twenty-seven healthy smokers, 21 males and 6 females, aged 20-41 years, were studied. On the study morning the subjects presented having fasted from 21h00 on the preceding evening and having refrained from cigarette smoking and from drinking caffeine-containing beverages during this period. According to a double-blind, crossover design, each subject was asked to smoke four cigarettes during a 1-hour period, 120 minutes after oral administration of celiprolol 200 mg or placebo. BP and HR were measured immediately before and 10 minutes after each smoking episode. BP was measured using a standard mercury sphygmomanometer (I-V Korotkoff phase); HR was evaluated by pulse palpation. Doubleproduct (SBP x HR), which is considered a reliable index of oxygen consumption [13], was also calculated. The statistical analysis of the data was performed by analysis of variance and Students t-test. The main results, expressed as mean values of SBP, DBP, HR, and double product before and after each smoking episode, are shown in Table 1. Under placebo, cigarette smoking induced an increase in SBP, HR, and double product, which was statistically significant after each smoking episode. DBP values were significantly affected only by the third and fourth cigarette smoked. After each smoking episode, the recovery towards baseline presmoking SBP and HR values became progressively slower, with a consequent progressive increase in the baseline values between the smoking episodes. These findings indicate that in heavy smokers the smoking-induced rise in BP values also persists in the intervals between smoking a cigarette and the following intervals, thus confirming previous reports [8,9,13]. The negative association between BP and cigarette smoking shown by epidemiological studies [14] could be explained by the fact that in such studies BP values were usually measured after a period of abstinence from smoking. Acute celiprolol administration reduced the baseline BP and HR mean values before the hour-long smoking period and significantly attenuated both the SBP and HR increase due to smoking, with a consequent reduction in the double product; the DBP increase was not significantly affected by the drug. These findings partially contrast with those reported with other beta blockers, particularly the non-~l-selective ones, which have been shown to attenuate the HR but not the BP increase due to smoking [4-9]. The effects of acute celiprolol administration on the cardiovascular responses to smoking are probably due to its peculiar pharmacological properties. Celiprolol combines ~l-antagonist and ~2-agonist activity and is provided with a nonadrenergic vasodilating action and a mild a2-adrenoceptor blocking influence [11,12]. In addition to all cardiac changes usually induced by beta blockade, these properties should lead to vasodilation. Probably due to such a vasodilating effect, celiprolol seems to counteract the pressor effect of cigarette smoking. Another point to be considered is the fact that some beta blockers are metabolized in the liver on first pass after absorption; as cigarette smoking stimulates first-pass metabolism, for a given dose the plasma concentration has been reported to reach only half that in nonsmokers, with consequent less effective BP control in smokers [15]. This problem may not occur with celiprolol, which is not metabolized in the liver. In conclusion, due to its capacity to attenuate the