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Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 127 records · Page 7Linked to original sources
PubMed1997

From the monitoring of severe to a survey of mild adverse effects of current antihypertensive therapy: the hidden side of the iceberg. The Scientific Committee of the Italian Pharmacoepidemiology Survey on Antihypertensive Therapy.

One of the most important causes of the unsatisfactory results of antihypertensive therapy in current medical practice is the difficulty in evaluating individual tolerability to the various antihypertensive agents. The methods commonly used, i.e. assessment in controlled studies of limited duration, or notification to pharmacovigilance authorities, clearly underestimate the problem. In order to obtain more correct information on antihypertensive practice, an Italian pharmacoepidemiological study has recently been planned, and the results of a pilot phase of this study are reported here.

Antihypertensive Agents↗
PubMed1997

The sympathetic nervous system in human hypertension.

While animal models of hypertension have clearly shown an increase in sympathetic activity, a similar demonstration in humans has been more difficult to obtain for methodological reasons. There is now clear evidence, however, of an increase sympathetic activity in essential hypertension by the finding of either an increase in plasma norepinephrine and an increase in muscle sympathetic nerve traffic. Among the mechanisms responsible for this sympathetic activation the arterial baroreflex may play a role although probably a non specific and late one. Central neural influences associated with an excessive hypothalamic response to stress may also be involved, but conclusive evidence is still lacking due to the difficulty of assessing cardiovascular reactivity to stress in man. A deeper insight into the features of human sympathetic cardiovascular control may be offered now by new techniques which allow neural cardiovascular regulation to be assessed in daily life through computer analysis of noninvasive ambulatory beat-by-beat blood pressure and heart rate recordings.

Animals↗
PubMed1997

Intermediate endpoints for atherosclerosis in hypertension.

BACKGROUND: Event-based trials of antihypertensive therapy, although they have been essential in showing the beneficial effects of antihypertensive therapy on cardiovascular morbidity and mortality, could not answer the question whether antihypertensive therapy influences the development of atherosclerosis. Trials using measurements of plaque growth as endpoints are necessary. METHODS: The traditional approach of using quantitative coronary arteriography for assessing the course of coronary artery disease during treatment cannot obviously be used in uncomplicated hypertensive patients. B-mode quantitative ultrasound assessment of intima-media thickness (IMT) of the carotid artery wall is now being used in several trials comparing different antihypertensive drugs. The major advantage of this approach is that it is non-invasive; it has also been demonstrated that IMT measurements are well reproducible. Limits of normality, definition of plaques and rate of growth of IMT in hypertension are still uncertain, however. Additionally, ultrasonographic techniques do not clearly distinguish between media and intima, and it is difficult to decide how many of the carotid wall lesions observed in hypertension are due to media hypertrophy related to hypertension or to intima changes related to atherosclerosis, although it is likely that the largest lesions have an atherosclerotic component. PREVALENCE AND CLINICAL SIGNIFICANCE OF IMT: Baseline data from two recent trials, the VHAS and the ELSA, indicate that carotid wall lesions are highly prevalent in hypertension, but the prevalence level obviously depends on the criteria used for defining these lesions. It is known that elevated systolic blood pressure is an important risk factor for carotid lesions, and epidemiological surveys have shown that increased carotid IMT is more frequently associated with history and signs of coronary artery or cerebrovascular disease. Some evidence from a prospective study is also available, and the VHAS findings support this conclusion. Trials of antihypertensive therapy using IMT as endpoint are, therefore, likely to provide clinically useful information.

Angiography↗
PubMed1997

Twenty-four-hour ambulatory blood pressure evaluation of antihypertensive agents.

EVALUATION OF A SMOOTH BLOOD PRESSURE RESPONSE TO TREATMENT: Smooth or uniform blood pressure control is an obvious goal of antihypertensive therapy, but it is difficult to assess by the traditional clinic blood pressure measurements. Ambulatory blood pressure monitoring is therefore increasingly being used to evaluate new antihypertensive drugs and to assess the adequacy of treatment. The use of ambulatory blood pressure monitoring is based on two assumptions: that treatment must be continuously optimal, and that more frequent blood pressure measurements during treatment, particularly at different times and during various types of activity and mental states, may lead to a more accurate assessment than infrequent measurements in the clinic. When ambulatory blood pressure monitoring is used, the effect of a given antihypertensive agent or of a given antihypertensive regimen can be tested on the average blood pressure values over 24 h, or on day- or night-time values. The actual verification of the achievement of a uniform reduction of blood pressure throughout the 24-h time span can be achieved by comparing 24-h blood pressure profiles before treatment and during treatment. The so-called trough: peak ratio is generally used in an attempt at a more quantitative assessment of smooth control. Recently, we have developed the Smoothness Index, defined as the ratio between the mean hourly change in blood pressure (calculated over the 24-h period), divided by the standard deviation of these hourly changes. We have some indication that this may be a more accurate measurement of smooth blood pressure control under therapy than trough: peak ratios. TWENTY-FOUR-HOUR BLOOD PRESSURE CONTROL BY IRBESARTAN: Ambulatory blood pressure assessments are important during the clinical testing of new antihypertensive agents. Our group recently performed a multicenter study to compare the anti-hypertensive effect of three irbesartan dose regimens (75 mg once a day, 150 mg once a day, 75 mg twice a day) and placebo as measured by 24-h ambulatory blood pressure monitoring and confirmed by office blood pressure measurements. All irbesartan regimens were significantly more effective than placebo. Irbesartan at 150 mg once a day provided clinically significant and sustained blood pressure reductions over a full 24 h and had the highest trough: peak ratio and Smoothness Index. No additional benefit was observed with twice-daily dosing using irbesartan at 75 mg compared with a single daily at 150 mg. Therefore irbesartan at a single daily dose of 150 mg offers real efficacy with the potential for greater ease of administration compared with twice-daily antihypertensive therapy.

Angiotensin Receptor Antagonists↗
PubMed1996

Analysis of the dynamics of renal vascular resistance and urine flow rate in the cat following electrical stimulation of the renal nerves.

In ten sino aortic denervated, vagotomized and aneasthetized cats, renal efferent nerves were stimulated for 30 s with trains of constant current pulses at frequencies in the range 5-30 Hz. The arterial pressure, heart rate, urine flow rate (electronic drop counter) and renal blood flow (electromagnetic technique) were recorded. Subsequent computer processing gave the true means of renal artery pressure (MRAP) and renal blood flow (MRBF) and hence the renal vascular resistance (MRVR), over each cardiac cycle. Recovery of MRVR after the end of stimulation exhibited two distinct time constants. The fast component had a time constant of 2.03 +/- 0.26 s and represented 60.2 +/- 1.71% of the recovery. The time constant of the slower component was 14.1 +/- 1.9 s and represented 36.0 +/- 1.6% of the recovery. The relationship between MRVR and stimulus frequency was sigmoidal with maximum sensitivity at stimulus frequencies of 12.6 +/- 0.76 Hz. Changes in urine flow rate, in contrast, followed a hyperbolic function with maximum response sensitivity occurring at very low stimulus frequencies. Changes in urine flow rate were 50% complete at stimulus frequencies of 5 Hz. Identification of two distinct components in the relaxation phase of renal vascular resistance leads to a reasonable hypothesis that 60% of total renal vascular resistance may lie proximal to the glomerulus, whereas 36% may be accounted for by the efferent arterioles.

Anesthesia↗
PubMed1996

Similarities and differences in structural and functional changes of left ventricle and carotid arteries in young borderline hypertensives and in athletes.

OBJECTIVE: To investigate the association between increased left ventricular mass and the intima-media thickening of carotid arteries in hypertensive patients and the simultaneous involvement of the heart and the conductance vessels by the hypertensive process. METHODS: Because no data are available concerning the ultrasonographic characteristics of large arteries in athletes with physiological increases in left ventricular mass, we measured the intima-media thickness (IMT) of the common carotid artery (CCA) in 14 normotensive subjects (group I, aged 22 +/- 4 years), in 14 borderline hypertensives (group II, aged 24 +/- 6 years) and in 14 Japanese wrestling players (group III, aged 23 +/- 4 years). The IMT of the posterior wall of the CCA was measured at 5, 10 and 20mm caudally to the bifurcation and the measurements were averaged. Left ventricular diameters and thicknesses of the interventricular septum and posterior wall were obtained from two-dimensionally guided M-mode tracings and measured according to the Penn convention. Left ventricular mass was calculated by the formula of Devereux. Left ventricular filling was measured by a pulsed Doppler technique. RESULTS: Both systolic and diastolic blood pressure values were significantly higher in group II (145 +/- 7/91 +/- 5 mmHg) than they were in group I (116 +/- 11/75 +/- 5 mmHg) and in group III (120 +/- 8/78 +/- 6 mmHg). In athletes and hypertensives both the left ventricular mass index and the IMT of the CCA were significantly greater than they were in control subjects (80 +/- 12 g/m2 and 0.45 +/- 0.05 mm in group I; 106 +/- 15 g/m2 and 0.57 +/- 0.08 mm in group II; and 122 +/- 17 g/m2 and 0.55 +/- 0.05 mm in group III). The mitral early:late peak flow velocity ratio was significantly lower in group II (1.9 +/- 0.58) than it was in the other two groups (2.3 +/- 0.66 in group I and 2.6 +/- 0.64 in group III). CONCLUSIONS: The results of our study suggest that both hypertension and physical training can induce parallel changes in cardiac and in arterial walls, and that physiological left ventricular hypertrophy in athletes is accompanied by a normal diastolic filling pattern in contrast to the pathological pattern found in hypertensives. Further investigation is required to explore possible differences in carotid structure and function between these two conditions.

Adult↗
PubMed1996

Safety of the calcium antagonist lacidipine evaluated from a phase III-IV trial database.

OBJECTIVE: We reviewed the clinical safety profile of lacidipine with the help of the rather comprehensive datafile of the manufacturer. Although a number of prospective, randomly allocated trials under way at present are investigating the effects of treatment with calcium antagonists on cardiovascular morbidity and mortality, these results are not yet available. Therefore, the present approach may be useful. A fuller account of this work has been published in Blood Pressure. DESIGN: Since 1985,50 phase III-IV trials have been performed to investigate antihypertensive efficacy in patients with hypertension; 32 were controlled trials with comparison treatment and 18 were open studies of lacidipine treatment. Only data from trials completed before 1 January 1995 are presented here. SUBJECTS: In all, 16590 patients were treated with lacidipine; 13419 in open studies and 3171 in double-blind comparative trials. A total of 1810 patients were given active comparative treatment and 451 were given placebo. Altogether, 5124 person-years of data were obtained. MAIN OUTCOME MEASURES: Numbers of both fatal and non-fatal cardiovascular events were estimated. Efficacy (change in blood pressure and heart rate), adverse event rates and drop-out rates were compared for the different treatment regimens. RESULTS: In all trials, 2-6 mg lacidipine was effective in lowering blood pressure. In the controlled trials, systolic/diastolic blood pressure fell from 166/102 to 144/85 mmHg and the heart rate fell from 75.6 to 74.1 beats/min. The estimated event rate for a possible myocardial infarction in all studies was 5.46/1000 person-years; the fatal (all-cause) event rate was 5.27/1000 person-years and the estimated fatal cardiovascular event rate was 2.93/1000 person-years. There were 21 malignant events during treatment with lacidipine, for all studies yielding a crude incidence of 4.10/1000 person-years. In patients treated with lacidipine, the age-standardized (according to the world population) incidences were 1.49 (men) and 0.79/1000 person-years (women) compared with 2.74 (men) and 2.09/1000 person-years (women) in the European Community in 1990. The overall incidence in the comparative studies of one or more adverse events included 30.3% for lacidipine, 43.8% for other calcium antagonists, 18.7% for diuretics, 48.7% for beta-receptor blockers, 10.4% for angiotensin converting enzyme inhibitors and 15.7% for placebo. The adverse effects of lacidipine were, as expected, headaches, flushing, pedal oedema and palpitations. CONCLUSIONS: Lacidipine proved to be an effective and well tolerated drug in almost 19000 hypertensive patients. It displayed a reasonable adverse profile that was typical of a calcium antagonist of the dihydropyridine group. This analysis has two obvious limitations: (1) it is a retrospective analysis; and (2) the data were obtained from a large cohort of patients, but most were treated with lacidipine for a relatively short period of time. Although we found a lower fatal event rate than that reported by Collins et al., their meta-analysis included 10 times more person-years than our analysis, and therefore our event rate may be less accurate. Further prospective studies are under way at present to determine whether these drugs can produce reductions in atherosclerosis or in the incidence of cardiovascular disease.

Adolescent↗
PubMed1996

Ambulatory blood pressure monitoring.

PREDICTIVE VALUE OF 24-H AMBULATORY BLOOD PRESSURE MONITORING: Average 24-h blood pressure values are more closely related to the target-organ damage of hypertension than are clinic blood pressure readings. Preliminary evidence from longitudinal studies suggests that ambulatory blood pressure is also superior to isolated clinic readings in the prognostic evaluation of hypertensive patients. This is supported by the demonstration that in hypertensive patients with left ventricular hypertrophy, regression of cardiac hypertrophy following treatment was better predicted by the drug-induced reduction in 24-h average blood pressure than clinic blood pressure. BLOOD PRESSURE VARIABILITY: Also, 24-h blood pressure variability seems to be involved in the genesis of hypertension target-organ damage, while the clinical value of specific components of the 24-h blood pressure profile, such the nocturnal blood pressure fall, is still a matter of debate. Similar caution is needed in approaching the clinical significance of white coat hypertension, the definition of which is still affected by important methodological problems.

Blood Pressure↗
PubMed1996

Trials investigating the anti-atherosclerotic effects of antihypertensive drugs.

METHODS OF CURRENT TRIALS: Several ongoing trials are investigating the anti-atherosclerotic effects of antihypertensive drugs in hypertensive patients. Changes in carotid intimal-medial thicknesses and atherosclerotic plaques are being explored by a sensitive quantitative B-mode ultrasound technique. MULTICENTER ISRADIPINE/DIURETIC ATHEROSCLEROSIS STUDY (MIDAS): The results from this pioneering study indicated a slower progression, at least in the first 6 months, of carotid plaques in isradipine-treated patients than in diuretic-treated patients. MIDAS has been particularly valuable in giving information on the rate of growth of intimal-medial thickness in hypertensive patients and on the best end-point to use in carotid ultrasound trials. EUROPEAN LACIDIPINE STUDY ON ATHEROSCLEROSIS (ELSA) AND VERAPAMIL IN HYPERTENSION AND ATHEROSCLEROSIS STUDY (VHAS): Baseline data from these two ongoing studies have provided evidence of the very high prevalence of carotid lesions among hypertensive patients: the prevalence of plaques (defined as a carotid intimal-medial thickness of > or = 1.3 mm) was 83% in ELSA, while in VHAS, in which plaques were defined as an intimal-medial thickness of > 1.5 mm), the plaque prevalence was 37%. These observations emphasize the importance of evaluating the atherosclerotic action of antihypertensive agents. PLAQUE HYPERTENSION LIPID-LOWERING ITALIAN STUDY (PHYLLIS): This trial is using a factorial design to explore the anti-atherosclerotic action of an angiotensin converting enzyme (ACE) inhibitor (fosinopril) versus a diuretic, and also intends to evaluate the possible benefits of associating antihypertensive therapy with a statin to induce lipid-lowering to prevent the progression of carotid atherosclerosis.

Antihypertensive Agents↗
PubMed1996

Current position of calcium antagonists in hypertension.

BACKGROUND: Periodically in the history of antihypertensive therapy, minor storms have significantly affected the use of entire classes of agents. An early example is the publication of case-control studies suggesting that reserpine was associated with increased risk of carcinoma of the breast, a claim subsequently disproved by a number of other studies. CONTROVERSY OVER USE OF CALCIUM ANTAGONISTS IN HYPERTENSION: A new controversy has developed recently with the publication of a case-control study report and a non-randomized cohort study which have questioned the use of calcium antagonists in hypertension. The case-control study suffers from the same disadvantages as the reserpine report and, indeed, another case-control study published in 1995, though not so well publicized, reached exactly opposite conclusions, claiming that calcium antagonists were significantly less associated with myocardial infarction than traditional antihypertensive therapy. A meta-analysis has also been presented in support of the non-randomized studies questioning the safety of calcium antagonists. However, this study refers to patients with coronary heart disease, not to patients with hypertension, and also suffers from lumping studies performed with different aims and using data from short-term and long-term studies on short-acting formulations of calcium antagonists. CONCLUSIONS: The controversy generated by these reports has gone well beyond their scientific merit. Well designed prospective studies are needed, and several of these are under way at present. For the time being there is no reason to change the current practice of antihypertensive therapy, as summarized in the recommendations of both the United States Joint National Committee and the World Health Organization/International Society of Hypertension Committee, that diuretics and beta-blockers are among those antihypertensive agents with more clearly proven benefit on the basis of mortality-morbidity studies, while calcium antagonists, angiotensin converting enzyme inhibitors and alpha-blockers can also be profitably used in the treatment of hypertension.

Calcium Channel Blockers↗
PubMed1996

Left ventricular concentric remodelling and carotid structural changes in essential hypertension.

AIM: Left ventricular concentric remodelling defines a modified left ventricular geometry in the presence of a normal left ventricular mass; it is an early and frequent adaptation in arterial hypertension. The present study was designed to evaluate the extent of carotid structural changes in essential hypertensives with left ventricular remodelling. PATIENTS AND METHODS: Two groups of hypertensive patients, who had never previously received anti-hypertensive treatment, 14 with left ventricular concentric remodelling (group I, relative wall thickness 0.48 +/- 0.02) and 48 with normal left ventricular geometry (group II, relative wall thickness 0.37 +/- 0.04) underwent clinical and laboratory examination, echocardiography, carotid artery ultrasonography and 24 h ambulatory blood pressure monitoring (ABPM). The left ventricular dimensions and mass were obtained according to the Penn convention. The intima-media thickness (IMT) of the posterior wall of both common carotid arteries was measured 5, 10 and 20 mm caudally to the bulb and the average value was used for analysis. RESULTS: In both groups age (group I 44 +/- 9 years; group II 40 +/- 9 years), body surface area (group I 1.85 +/- 0.2 m2; group II 1.80 +/- 0.2 m2), duration of hypertension (group I 4.4 +/- 4; group II 3.8 +/- 3.9 years), metabolic parameters and smoking habits were similar. Both clinic and 24 h ABPM values were higher in group I (clinic 157 +/- 12/102 +/- 5; 24 h ABPM 145 +/- 10/95 +/- 7 mmHg) than they were in group II (clinic 146 +/- 11/97 +/- 5; 24 h ABPM = 134 +/- 10/87 +/- 8 mmHg, P < 0.01). The left ventricular mass index (LVMI) and IMT were found to be slightly but significantly greater in group I than they were in group II (LVMI 106 +/- 7 versus 98 +/- 12 g/m2, P < 0.05; IMT 0.68 +/- 0.13 versus 0.61 +/- 0.10 mm, P < 0.05). A significant correlation was found between LVMI and common carotid IMT in the whole group of hypertensive patients (r = 0.43, P < 0.01). CONCLUSIONS: Our results indicate that left ventricular concentric remodelling does not represent the only early cardiovascular change in arterial hypertension but rather is associated often with carotid intima-media thickening.

Adult↗