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Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 37 records · Page 2Linked to original sources
PubMed1994

Hyperlipidemia in the hypertensive patient.

Hypertension is known to be strongly associated with multiple metabolic abnormalities. A recent population survey carried out in Italy (the Gubbio study) involving 5,376 individuals showed that, up to the age of 64 years, hypertensive men were more markedly overweight (body mass index > or = 30) than normotensive men, whereas in women the prevalence of obesity was higher in hypertensive women at all ages. The prevalence of marked hypercholesterolemia (> or = 250 mg/dL) was uniformly higher in hypertensive compared with normotensive men except in the oldest age group; it was also higher in hypertensive women in the age 45-74 years group. Postabsorptive hyperglycemia and hyperuricemia were also more prevalent in hypertensive men and women, especially in the older age groups. Furthermore, the Tecumseh Blood Pressure Study indicated that not only patients with "sustained" hypertension but also those with so-called "white-coat" hypertension are, as a group, overweight and have elevated levels of cholesterol, insulin, and triglycerides and decreased levels of high-density lipoprotein. The multiple metabolic abnormalities clustered in hypertensives are important in relation to prognosis and therapy. The most recent World Health Organization/International Society of Hypertension guidelines for management of mild hypertension give considerable attention to the global assessment of cardiovascular risk in patients with hypertension and stress that, among individuals with mild hypertension, the risk of serious cardiovascular disease is also determined by a variety of risk factors other than blood pressure. The higher the absolute risk, the greater is the absolute benefit brought about by lowering blood pressure and correcting other risk factors, such as dyslipidemia.

Adult↗
PubMed1994

Goals of antihypertensive treatment and planning of therapeutic trials.

The prevention of both cardiovascular events and organ damage or disease have to be considered to be different, but essential, goals of antihypertensive therapy. As the mechanisms that lead to organ damage and to events are, to a significant extent, different, it must be recognized that the achievement of the two goals has to be evaluated through trials using, separately or conjointly, different criteria. Thus far, randomized trials of antihypertensive therapy have almost exclusively measured mortality and morbidity data, and have provided information relevant to the prevention of cardiovascular events in those hypertensive patients in whom a relatively high rate of events is expected during the relatively short time span (3 to 6 years) of the trial, namely, those who have severe hypertension or who are elderly. However, in young or middle-aged patients with mild-to-moderate hypertension, for whom the goal of therapy would be to prevent or retard the development of vascular lesions to help these patients achieve their full life span, trials should be based on the measurement of organ damage rather than, or in addition to, the monitoring of events. The MIDAS trial has been the first in which two different modes of antihypertensive therapy have been tested for their capacity to influence the development of atherosclerosis in hypertension. It is likely that the results of this study will prompt many more therapeutic trials based on the quantitative assessment of organ damage in hypertension.

Antihypertensive Agents↗
PubMed1994

Hemodynamic and humoral effects of chronic treatment with the neutral endopeptidase inhibitor SCH 42495 in spontaneously hypertensive rats.

Blockade of atrial natriuretic factor (ANF) degradation by specific neutral endopeptidase (NEP) inhibitors may be useful in treatment of hypertension because of the potential diuretic, natriuretic, and arterial pressure (AP)-lowering effects. To test this possibility, we examined the effects of chronic oral treatment with the NEP inhibitor SCH 42495 on BP, diuresis, natriuresis, plasma ANF, cyclic GMP, and the renin-angiotensin system (RAS) in conscious unrestrained spontaneously hypertensive rats (SHR) and compared them with the effects induced by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPIR). Four groups of adult SHR were treated orally for 4 weeks with placebo, SCH 42495 3 mg/kg twice daily (b.i.d.), SCH 42495 30 mg/kg b.i.d., and spirapril 1 mg/kg b.i.d. Systolic BP (SBP) was measured weekly, and 24-h urine was collected every week for measurement of urinary volume, sodium, potassium, and cyclic GMP excretion. Plasma ANF, cyclic GMP, renin activity (PRA), and aldosterone (ALDO) were determined from blood collected when the rats were killed. After 4-week treatment with SCH 42495, circulating levels of ANF were similar in both SCH 42495- and placebo-treated SHR; plasma cyclic GMP was higher, however, in the treated rats than in controls and urinary cyclic GMP increased only with the higher dose of SCH 42495. PRA and plasma ALDO tended to be lower in both SCH 42495-treated groups than in controls, yet BP, diuresis, and natriuresis throughout the study were not different from controls. In contrast, spirapril decreased BP; this effect was associated with significant increments in renin and decrements in ALDO and ANF, without changes in plasma and urinary cyclic GMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Ambulatory and home blood pressure normality: the Pamela Study.

Ambulatory blood pressure monitoring (ABPM) is increasingly used in the clinical evaluation of hypertension. However, a number of limitations restrict its routine use. One of the limitations is a lack of definite conclusions about ambulatory blood pressure normality, because of the shortcomings of previous studies on this issue. In the present study we describe a survey from a large sample of subjects within the age range of 25-64 years. It was found that 24-h average systolic and diastolic blood pressures are markedly lower than clinic blood pressure, and for daytime average and home blood pressure as well. In addition, it was found that the clinic ambulatory or home blood pressure disparity is related to the baseline clinic blood pressure (i.e., it increases with increasing clinic blood pressure values) and that the three pressures (ambulatory, home, clinic) are closely related to each other, thereby allowing the application of correction factors to obtain information on ambulatory or home blood pressure normality. This results in an upper normality limit for 24-h average blood pressure and home blood pressure of around 120 mm Hg systolic and 77 mm Hg diastolic pressure.

Adult↗
PubMed1994

The 24-hour efficacy of a new once-daily formulation of nifedipine. Italian Nifedipine GITS Study Group.

Nifedipine GITS (Gastro-Intestinal Therapeutic System) is a recently launched long-acting formulation of nifedipine. The aim of the Italian Nifedipine GITS Study was to determine the duration of the antihypertensive effect of once-daily nifedipine GITS in outpatients with essential hypertension. After a 2-week placebo run-in period, 126 patients with mild to moderate essential hypertension (diastolic BP95 to 114mm Hg) were randomised to receive nifedipine GITS 30mg (n = 42), nifedipine GITS 60mg (n = 42) or placebo (n = 42), once daily in a double-blind fashion for 4 weeks. At the end of the run-in and treatment periods, ambulatory BP monitoring was performed (Spacelabs 90202 or 90207 device) to provide regular 15-minute BP readings for 24 to 36 hours. In the 81 patients with at least 24 hours of valid ambulatory BP data, the average systolic and diastolic BP changes after treatment with nifedipine GITS 30mg (n = 25), nifedipine GITS 60mg (n = 28) and placebo (n = 28) were -16.5/-10.8, -16.3/-10.0 and +0.4/+0.9mm Hg, respectively. BP changes with nifedipine GITS differed significantly (p < 0.01) from those with placebo. Heart rate was not significantly altered by nifedipine GITS. The effects of nifedipine GITS and placebo on ambulatory BP 24 hours and 36 hours after the last dose were evaluated in 56 patients with complete 36-hour ambulatory BP profiles. After 24 hours, both doses of nifedipine GITS caused significant (p < 0.01) reductions in systolic and diastolic BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The Hypertension Optimal Treatment (HOT) Study--patient characteristics: randomization, risk profiles, and early blood pressure results.

The Hypertension Optimal Treatment (HOT) Study is a prospective, randomized, multicenter trial being conducted in 26 countries. Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and cardiovascular morbidity and mortality in hypertensive patients. In addition, the study will examine the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) or placebo. In the HOT Study, basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily. If target blood pressure is not reached, additional antihypertensive therapy with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent is given. Further dosage adjustments are made in accordance with a set protocol. As a fifth and final step, a diuretic may be added. Inclusion of patients was stopped on April 30, 1994. At that time 19,196 patients had been randomized. There were 9,055 (47%) women and 10,141 (53%) men with an average age of 61.5 +/- 7.5 (SD) years. At enrollment, 52% of patients were receiving antihypertensive treatment. These patients entered a wash-out period of at least 2 weeks before randomization. The average randomization blood pressure in untreated patients was 169 +/- 14/106 +/- 3 mmHg and in the treated patients 170 +/- 14/105 +/- 3 mmHg. On August 15, 1994, blood pressure data were available for 14,710 and 10,275 patients, who had completed 3 and 6 months treatment, respectively. The average reduction in diastolic blood pressure was 22 mmHg after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1994

Coronary vascular reactivity and calcium antagonist therapy in patients with angina.

In patients with severe coronary atherosclerotic disease, the angiotensin-converting enzyme inhibitor captopril attenuates the vasoconstriction induced by the cold pressor test and diving (two stimuli that cause reflex sympathetic activation) via removal of the facilitating effect of angiotensin II on sympathetic drive. However, whether calcium antagonists also have this effect is not clear. We evaluated the effects of a single 11-mg intravenous dose of the dihydropyridine calcium antagonist amlodipine on the coronary vascular response to the cold pressor test, a 30-s application of the dive reflex and cigarette smoking (whose effects on the coronary circulation also involve the sympathetic nervous system). In 13 normotensive male patients with severe stenoses of the left anterior descending coronary artery, the cold pressor test and diving reflex increased mean arterial pressure and rate-pressure product and caused a marked and significant rise in coronary vascular resistance (+ 12.1 +/- 4.8% and +30.4 +/- 6.8%, respectively). Mean arterial pressure, rate-pressure product, and coronary vascular resistance also increased markedly during smoking. Amlodipine caused a reduction in baseline mean arterial pressure, an increase in baseline coronary blood flow, and a marked fall in baseline coronary vascular resistance (-19.2 +/- 3.1%; p < 0.01). The coronary vascular responses to the cold pressor test and the diving reflex were unchanged with amlodipine. However, the smoking-induced increase in coronary vascular resistance was significantly attenuated after amlodipine (+3.2 +/- 2.7% vs. +16.8 +/- 7.2%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine↗
PubMed1994

[Which is the optimal pressure level to be obtained with antihypertensive treatment?].

To what level blood pressure should be brought by antihypertensive treatment is a question with relevant clinical bearing that hypertensiologists have regrettably not yet investigated in a direct way. As a consequence of the lack of direct data on this problem, a dispute has been going on for some time as to whether a decrease in blood pressure below 85 mmHg increases, rather than further decreasing, the coronary risk of the hypertensive patients (the "J-curve" hypothesis). The problem has been finally approached through the design and the initiation of an appropriate large controlled trial, the Hypertension Optimal Treatment (HOT) study.

Aged↗
PubMed1994

Treatment perspectives in hypertension.

Despite the considerable progress in our understanding of the mechanisms of hypertension-related cardiovascular damage, assessment of treatment benefit is so far based on randomized trials monitoring cardiovascular events only. There are inherent limitations to this approach. First, the mechanisms precipitating events are partly different from mechanisms leading to the underlying vascular injury, and evidence obtained on therapeutic prevention of events cannot be automatically applied to therapeutic prevention of disease. Second, event-based trials are suitable to test treatment effectiveness only in those conditions, such as severe hypertension and hypertension in the elderly, in which a high rate of events is expected during the necessarily short duration of the trials. Third, in young and middle-aged patients with mild hypertension, event-based trials are likely to have markedly underestimated treatment benefits. Fourth, in these patients the benefits of antihypertension therapy can be better explored by trials monitoring the progress of organ damage than by trials monitoring the occurrence of events. Finally, trials monitoring organ damage are now feasible as new quantitative, sensitive, and reliable techniques are available. Both prevention of cardiovascular events and prevention of organ damage and disease are essential goals of antihypertension therapy, and achievement of these two distinct goals has to be evaluated through trials using different types of criteria.

Adult↗
PubMed1994

Trough:peak ratio of the blood pressure response to dihydropyridine calcium antagonists. Italian Nifedipine GITS Study Group.

OLD VERSUS NEWER DIHYDROPYRIDINE CALCIUM ANTAGONISTS: First-generation dihydropyridines have a short duration of antihypertensive action, which requires more than one daily dose in order to produce a relatively 'smooth' antihypertensive effect. However, more recent molecules or preparations have been shown to possess a much longer and smoother action. TROUGH:PEAK RATIOS OF NIFEDIPINE GASTROINTESTINAL THERAPEUTIC SYSTEM (GITS): The Italian Nifedipine GITS Study has shown, by using ambulatory blood pressure monitoring for 24-36 h, that nifedipine GITS, a new slow-release preparation, is capable of producing a marked reduction in both systolic and diastolic blood pressure that extends to 30-36 h after the dose. In this study, nifedipine GITS produced a smooth antihypertensive effect throughout the dose interval of 24 h by whatever method was used to evaluate this effect: (1) hourly blood pressure profiles; (2) trough:peak ratios, corrected or uncorrected by placebo effects (ratios often approached 100%); (3) calculation of individual trough:peak ratios in all treated patients (60% of whom had ratios of > 50%); and (4) calculation of individual trough:peak ratios in 'responders' to nifedipine GITS (approximately 75% of whom had ratios of > 50%). USE OF AMBULATORY BLOOD PRESSURE MONITORING: The large body of data on ambulatory blood pressure monitoring provided by this study has also allowed comparison and analysis of the advantages and disadvantages of the various methods of assessing the smoothness of the antihypertensive action of a drug by ambulatory blood pressure monitoring.

Blood Pressure↗
PubMed1994

Hemodynamic and neural effects of urapidil and prazosin in essential hypertensives.

Assessment of the effects of antihypertensive drugs on sympathetic cardiovascular modulation is aimed not only at exploring the neural mechanisms of the hypotensive action of different pharmacological compounds but also at evaluating the effects of these drugs on neural cardiovascular homeostatic control. This paper, after reviewing the effects of different antihypertensive drugs on efferent postganglionic muscle sympathetic nerve activity directly assessed in man via the microneurographic technique, will report the preliminary results of a study we have recently performed in 12 untreated mild essential hypertensives. This study was aimed at examining the effects of a single oral administration of either the hybrid drug urapidil (30 mg) or the pure alpha-blocker prazosin (2 mg) on arterial blood pressure (Finapres technique), heart rate (electrocardiogram) and muscle sympathetic nerve activity (microneurography at the peroneal nerve). For similar blood pressure reductions, urapidil caused a lesser degree of tachycardia in comparison with prazosin (+5.1 +/- 1.2 vs +8.4 +/- 0.8 beats/min, p < 0.05) but superimposable increases in muscle sympathetic nerve traffic (+15.4 +/- 2.8 vs 17.5 +/- 3.5 bursts/min). These results suggest that the two drugs induce similar degrees of blood pressure reduction as well as of muscle sympathetic activation. Urapidil, however, is accompanied by less tachycardia than prazosin, presumably because of a selective drug's action on either parasympathetic or sympathetic modulation of heart rate, triggered by the stimulation of central 5HT1A-receptors.

Administration, Oral↗
PubMed1994

Urapidil in hypercholesterolemic hypertensive patients.

The association of arterial hypertension and hyperlipidemia strikingly enhances prevalence, incidence and mortality of cardiovascular disease. In the light of recent evidence that some antihypertensive drugs with alpha-1 blocking properties reduce blood pressure (BP) and total cholesterol (chol), increasing chol content in the non-atherogenic high density lipoproteins (HDL-chol), the effects of urapidil, a peripheral alpha-1 adrenoceptor antagonist, with a central action component on BP and plasma lipids were evaluated in 49 mild, hypertensive patients with mild to moderately severe hypercholesterolemia (serum chol 220-320 mg/dl) for a 6 month period in a double-blind randomized study versus placebo. Five out of the 49 patients (3 on urapidil, 2 on placebo) discontinued treatment due to adverse side effects. Five patients on placebo did not meet protocol requirement of serum triglycerides < 350 mg/dl (3.95 mmol/L) and were only included in the BP efficacy assessment. The groups of urapidil and placebo were comparable for age (50 +/- 10 vs 49 +/- 7 years), body weight (72 +/- 9 vs 73 +/- 10 kg), sex (18M, 8F vs 14M, 9F) and mean arterial pressure (119.4 +/- 4 vs 119.7 +/- 4 mmHg). The actively treated group significantly decrease BP values from 159/99 +/- 13/2 to 152/90 +/- 23/8 mmHg, whilst no change was observed in the placebo group. Between group analysis showed a significant difference at the end of treatment (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1994

Effects of amlodipine on coronary hemodynamics and vascular responses to sympathetic stimulation in patients with coronary heart disease.

Dihydropyridines (DHPs) exert a powerful coronary vasodilator action, but whether they actually affect the coronary vasomotor effects elicited by an increase in cardiac sympathetic drive is controversial. We assessed the effects of the DHP calcium antagonist amlodipine on coronary hemodynamics and vascular response to sympathetic activation in patients with coronary heart disease. In the control condition, mean arterial pressure (MAP, aortic catheter), heart rate (HR, ECG), rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution) and coronary vascular resistance (CVR) (ratio between MAP and CBF) were measured in all our case series (13 patients with angiographically documented severe coronary artery disease) before and during a 2-min cold pressor test (CPT) and a 30-s diving (D) and, in the 8 patients of this case series who were smokers, also before and during smoking a cigarette (S, nicotine content 1.0 mg for 10 min). The same protocol used in control condition was repeated 30 min after intravenous (i.v.) bolus administration of 11 mg amlodipine. CPT, diving, and smoking increased MAP and RPP and caused a marked and significant increase in CVR (+12.1 +/- 4.8, +30.4 +/- 6.8, and +16.8 +/- 7.2%, respectively). Amlodipine reduced MAP, increased CBF, and caused a marked decrease in CBF. The drug did not modify responses to CPT and diving or pressure and HR responses to smoking, whereas the smoking-induced increase in coronary vascular resistance was attenuated after amlodipine administration (+3.2 +/- 2.7%, p < 0.05 vs. control condition). Thus, amlodipine does not attenuate the sympathetic coronary vasoconstrictor effects of CPT and diving.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The physiologic relevance of smooth twenty-four-hour blood pressure control.

UNLABELLED: Concept of smooth 24-h blood pressure control: Smooth 24-h blood pressure control is an obvious goal of antihypertensive therapy, but it is difficult to measure and its clinical impact is difficult to verify. The term 'smooth' is of uncertain significance. Clearly, normal 24-h blood pressure varies between resting periods and periods of activity. If, however, the concept means, as commonly used, that in treated hypertensives blood pressure during the 24-h period should be superimposable on the daily blood pressure values and fluctuations in normotensive subjects, then the concept is valid. But this definition raises the even more complex and difficult issue of how to define hypertension and normotension. Attempt to define normal ambulatory blood pressure values: An attempt to establish normal reference values for ambulatory blood pressure in an epidemiologic context is underway. Preliminary data from the PAMELA study indicate that both 24-h means and home blood pressure values are several millimeters of mercury lower than clinic blood pressures. In order to identify the ideal blood pressure profile to be achieved by therapy, there are two additional aspects to be clarified. One is whether it is daytime or night-time blood pressure that should be more effectively normalized by treatment; the other is whether a reduction in blood pressure variability should also be among the goals of antihypertensive treatment. CONCLUSION: Despite expanding use of ambulatory blood pressure monitoring and increasing information on blood pressure profiles during treatment, we are still far from fully understanding the impact of ambulatory blood pressure monitoring on the management of hypertension.

Antihypertensive Agents↗
PubMed1994

Trough and peak effects of a single daily dose of nifedipine gastrointestinal therapeutic system (GITS) as assessed by ambulatory blood pressure monitoring. Italian Nifedipine GITS Study Group.

AIM: To evaluate the antihypertensive efficacy of nifedipine gastrointestinal therapeutic system (GITS), a slow-release formulation of nifedipine. PATIENTS AND METHODS: A randomly allocated, double-blind, placebo-controlled trial was set up with 126 essential hypertensives who were assessed by ambulatory blood pressure monitoring. A 2-week placebo run-in phase was followed by treatment with nifedipine GITS at 30 mg (n = 42) or 60 mg (n = 42) or with a placebo (n = 42) once a day for 4 weeks. At the end of each period, 24- to 36-h ambulatory blood pressure was measured at 15-min intervals by a SpaceLabs 90202 or 90207 device. The peak effect of nifedipine was assessed as the lowest average hourly value of systolic/diastolic blood pressure 2-6 h after drug intake subtracted from the baseline value for the same hour, and the trough effect as the mean systolic/diastolic blood pressure obtained 24 h after the dose subtracted from the baseline value for the same hour. RESULTS: In the 81 patients with 24-h valid ambulatory blood pressure data, 24-h, daytime and night-time mean systolic and diastolic blood pressures were significantly decreased by nifedipine GITS at both doses, but were not changed by the placebo. The trough: peak ratios for systolic and diastolic blood pressure were 90.5 and 76.3% for 30 mg nifedipine GITS and 109.3 and 98.6% for 60 mg nifedipine GITS. Correction by trough and peak effects in the placebo group further increased the trough: peak ratios. In 51 patients with 36-h ambulatory blood pressure data, trough: peak ratios above the United States Food and Drug Administration recommended value of 50% were found 30 h after the dose, and systolic blood pressure was still significantly lower 36 h after the nifedipine GITS dose.

Blood Pressure↗
PubMed1994

Cardiovascular consequences of hypertension: therapeutic effects on organ damage and on cardiovascular events.

All major randomized trials that have tested the effectiveness of antihypertensive therapy have exclusively or almost exclusively been based on mortality and morbidity data (fatal and non-fatal strokes, fatal and non-fatal myocardial infarctions, sudden cardiac deaths, cardiovascular mortality, mortality by any cause). Thus, trials based on the monitoring of events have succeeded in ascertaining the achievement of the most important goals of treatment of any morbid condition--the prolongation of life and prevention of incapacitating morbid events. However, a clear distinction has to be made between cardiovascular events, as measured in any randomized trial of antihypertensive therapy, and the underlying vascular lesions, which have never been measured in large randomized therapeutic trials. Therefore, the results of therapeutic trials based on events cannot be applied towards the conclusion that antihypertensive therapy has similar effects on the underlying disease. Indeed, the mechanisms responsible for the precipitation of events are often different from the mechanisms leading to disease. Both the prevention of cardiovascular events and prevention of organ damage or disease are essential goals of antihypertensive therapy. As the mechanisms leading to vascular injury and to events are, to a significant extent, different, the achievement of the two goals has to be evaluated through trials that use, separately or conjointly, different criteria--either cardiovascular events, or one or more measures of cardiovascular injury. Trials based on cardiovascular injury are now possible due to the relatively large number of quantitatively precise and reproducible techniques for evaluating organ damage accompanying hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗