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Biomedical subjects

G Mancia

Publications and source records attributed to G Mancia.

At least 235 records · Page 13Linked to original sources
PubMed1996

INSIGHT: international nifedipine GITS study intervention as a goal in hypertension treatment.

The objective of the study is to compare fatal and nonfatal cardiovascular endpoints in hypertensive patients randomised to the calcium-channel blocker, nifedipine GITS or a thiazide diuretic, co-amilozide. A total of 6592 patients from nine countries (UK, France, Israel, Spain, Italy, The Netherlands, Sweden, Denmark and Norway) will be recruited, aged 55-80 and with a blood pressure (BP) > or = 150/95 or > or = 160 mm Hg (systolic). All patients will have at least one other major cardiovascular risk factor. Patients will be minimised by country and risk factors and randomised to double-blind treatment with either nifedipine GITS or diuretic. After a single dose titration, additional treatment will be atenolol or enalapril (where beta-blockade is contra-indicated). After achieving a target BP of 140/90 mm Hg patients will be followed for a total of 3 years. Primary endpoints are myocardial infarction, stroke, subarachnoid haemorrhage, heart failure and sudden cardiac death. The study has a power of 80% at 5% significance to detect a difference between 8% event rate over 3 years in diuretic-treated patients and 6% in those receiving nifedipine.

Aged↗
PubMed1996

Attempts to improve the selectivity of calcium antagonistic drugs.

The dihydropyridine calcium antagonists differ in respect to their structures as well as their pharmacological profiles. An improved vascular selectivity has been claimed for some of the newer agents (amlodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine and nicardipine), implying that these agents exert a stronger action on the resistance and coronary arteries than on myocardial and nodal structures. By virtue of their antihypertensive effects, calcium antagonists should be considered as renal protective. Such a renal protective potential has been demonstrated in renal insufficiency and toxicity caused by cancer chemotherapy, radiocontrast agents, cyclosporine or aminoglycoside antibiotics. Furthermore, calcium antagonists may also have a protective effect on donor kidneys in kidney transplantation. Among the newer dihydropyridines, manidipine has been suggested as possessing a certain degree of renal selectivity. This claim is based mainly on animal experimental studies and has to be substantiated in the clinic. From the therapeutic point of view, the concept of renal selectivity for calcium antagonists may be of considerable interest.

Calcium Channel Blockers↗
PubMed1996

Obesity and the sympathetic nervous system.

Several epidemiological studies have shown that obesity represents an independent risk factor for development of cardiovascular diseases, including hypertension, myocardial ischaemia, and cardiac arrhythmias. Although the metabolic and the haemodynamic alterations occurring in the obese state have been well defined for several years, our knowledge on the sympathetic alterations occurring in this condition is more scarce and controversial. This paper reviews the evidence that human obesity is characterized by abnormalities in sympathetic cardiovascular control, in the light of the results of recent studies performed by employing a sensitive technique to assess sympathetic activity in humans, i.e. microneurography. Evidence is provided that sympathetic overactivity is a common hallmark of the obese state, even when blood pressure levels are within the normal range. It will also discuss the potential mechanisms responsible for this sympathetic activation, suggesting that overweight-related metabolic alterations, such as the insulin resistance state, and abnormalities in sympathetic cardiovascular control exerted by arterial baroreceptors may play a pathogenetic role. Finally, the effects of body weight reduction on the sympathetic overactivity which characterizes the obese state will also be examined.

Energy Intake↗
PubMed1995

Vascular wall thickness in hypertension: the Perindopril Regression of Vascular Thickening European Community Trial: PROTECT.

A high prevalence of increased intima/media thickness of the arterial wall has been documented in hypertension. These alterations in vascular wall structure may be potent determinants for the promotion of the development of atherosclerosis. Direct histologic data from animal models of hypertension, and indirect data from hypertensive patients, have demonstrated a marked regression of increased intima/media thickness by angiotensin-converting enzyme (ACE) inhibition. Long-term effects of ACE inhibition on structural wall changes in humans have not been examined. Therefore, a multicenter, randomized, double-blind European trial was designed to compare the effects of the ACE inhibitor perindopril and the diuretic hydrochlorothiazide in slowing or reversing progression of increased intima/media thickness of carotid and femoral arteries in hypertensive patients. A total of 800 patients at 17 clinical centers in 7 European countries, aged 35-65 years, with hypertension and ultrasonographically proven intima/media thickness > or = 0.8 mm of the common carotid artery will be randomly assigned to receive in a double-blind fashion either perindopril or hydrochlorothiazide and will be followed for 24 months. High resolution duplex sonography will be used to quantify intima/media thickness at baseline and twice a year during follow-up. A change of 0.1 mm of intima/media thickness from baseline is considered to be detectable, and the standard deviations of the changes from baseline are expected not to be higher than 0.2 mm. The primary endpoint of the study is the comparison of changes in intima/media thickness of the common carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Alterations of radial artery compliance in patients with congestive heart failure.

Congestive heart failure is accompanied by several hemodynamic alterations. To investigate whether these alterations include reduced arterial compliance, we studied 25 patients (age 57 +/- 2 years, mean +/- SE) with a mild or severe congestive heart failure based on clinical symptoms (New York Heart Association class II vs III or IV) and on echocardiographic alterations of left ventricular diastolic diameter and ejection fraction. Radial artery diameter and blood pressure were continuously measured by Doppler ultrasonography and a finger pressure device, respectively. Compliance was calculated by the Langewouters formula, and compliance values were derived throughout the systolic-diastolic pressure range. The area under the compliance-pressure curve normalized for pulse pressure was used to compare compliance values in the various groups. Data were obtained both in baseline condition and at the release from a 12-minute brachial artery occlusion. Fourteen healthy, age-matched subjects served as controls. Compared with the control group, patients with severe congestive heart failure showed a reduction of baseline compliance index (-48%, p < 0.01). Furthermore, while in control subjects compliance markedly increased after brachial artery occlusion (+43%, p < 0.01), in patients with severe congestive heart failure no increase occurred. No baseline compliance alteration was seen in patients with mild congestive heart failure in whom, however, the postischemic increase in compliance was also significantly blunted (-50% vs controls, p < 0.05). Thus, arterial compliance and arterial compliance modulation are impaired in congestive heart failure. Although more marked in severe congestive heart failure, the impairment is manifest in mild congestive heart failure as well.

Blood Pressure Determination↗
PubMed1995

Blood pressure variability and reflex control in the elderly.

Several lines of experimental and clinical evidence collected over the past ten years suggest that the aging process is characterized not only by profound structural cardiovascular alterations, but also by marked functional changes in the reflex mechanisms involved in the homeostatic control of the circulation. This paper will examine how aging affects baroreceptor control of the heart and sympathetic nerve traffic, providing evidence that while the former is markedly impaired in the elderly, the latter is virtually preserved. It will also discuss the age-related alterations in cardiopulmonary receptor function that, under physiological conditions, tonically inhibit sympathetic vasoconstriction tone and renin release from the kidney. Finally, evidence will be provided showing that short- and long-term blood pressure variabilities (and the different components of blood pressure variability) over 24 hours undergo major changes in the elderly. All these alterations in neural cardiovascular control mechanisms have clearcut clinical implications representing a potential marker of the increased cardiovascular risk which characterizes elderly people.

Aged↗
PubMed1995

Lack of placebo effect on ambulatory blood pressure.

Several studies have reported that, at variance with clinic blood pressure, ambulatory blood pressure is not reduced by treatment with placebo. However, this evidence has usually been obtained in small groups of subjects and no data are available from a larger sample of patients. To address this issue we have analyzed data from 116 outpatients involved in placebo-controlled studies on antihypertensive treatment. The patients were studied before and at the end of a 6- to 8-week period of placebo. In all patients, blood pressure was measured by sphygmomanometry and over the 24 h by automatic ambulatory monitoring. Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressure (-5.3 +/- 1.1 and -4.4 +/- 0.6 mm Hg, respectively; P < .01), but not in 24-h, daytime and nighttime blood pressure. Hourly systolic and diastolic blood pressure profiles were virtually superimposable in the two different periods, except for the first 4 h, in which systolic blood pressure was slightly but significantly lower during than before placebo (149.5 +/- 1.2 v 146.4 +/- 1.2 mm Hg; P < .05). These results provide a large database indicating that 24-h average blood pressure is not reduced by placebo, thus it is not necessary to include a placebo control group in antihypertensive drug studies in which ambulatory blood pressure monitoring is employed. A small placebo effect occurs, however, in the first hours of ambulatory monitoring. This may lead to a slight overestimation of the peak blood pressure effect of a drug and an underestimation of its trough-to-peak ratio if placebo correction of the data is not made or if the first part of ambulatory blood pressure monitoring is not excluded from data analysis.

Blood Pressure↗
PubMed1995

Permanent blood pressure control over the 24 h by trandolapril.

Noninvasive ambulatory blood pressure monitoring (ABPM) has proved to be an innovative tool for the assessment of the efficacy of antihypertensive drugs. It enables evaluation of the magnitude of the drug-related blood pressure fall and also of the duration of this effect throughout 24 h. Moreover, ambulatory blood pressures have advantages compared to office blood pressure: they are not affected by the white coat effect occurring at the time of the doctor's visit, are devoid of a placebo effect, are more reproducible than occasional clinic measurements, and may yield important information on the prognosis of hypertensive patients. Ambulatory blood pressure recordings were used to test the antihypertensive effect of a novel angiotensin converting enzyme, trandolapril, in 62 mild to moderate essential hypertensive outpatients. After a 4 week wash-out, period, patients were randomized to 2 mg trandolapril or placebo for 6 weeks. A 4-week wash-out period was scheduled at the end of the treatment period. Ambulatory blood pressure recordings were performed at the end of each period, starting in the morning. Trandolapril (n = 31) significantly reduced 24 h systolic and diastolic blood pressure as compared to pre- and posttreatment periods and to placebo (n = 17). The reduction involved both the daytime and nighttime blood pressure values and was evident also in the last hours of the recording, the trough-to-peak ratio being 0.6 for systolic and 0.7 for diastolic blood pressure. Thus, trandolapril at a dose of 2 mg once daily is an effective long-lasting antihypertensive drug.

Adult↗
PubMed1995

Structural cardiovascular alterations and blood pressure variability in human hypertension.

AIM: To evaluate the cardiovascular risk of hypertensive patients in relation to left ventricular hypertrophy, arteriolar hypertrophy and blood pressure variability, and the effects of antihypertensive treatment. LEFT VENTRICULAR HYPERTROPHY: In hypertensive subjects with marked left ventricular hypertrophy, cardiovascular problems are about three times more frequent than in hypertensives who do not have left ventricular hypertrophy. The evidence suggests, however, that a moderate degree of left ventricular hypertrophy may be compensatory and that regression of mild hypertrophy should not necessarily be pursued. ARTERIOLAR HYPERTROPHY: An increased wall to lumen ratio leads to an increase in vascular resistance and thus promotes hypertension. Regression of this alteration with antihypertensive treatment appears to be both beneficial and achievable, although it is not clear whether all antihypertensive agents have the same effect. Moreover, there are methodological problems in determining whether a regression has actually been achieved. BLOOD PRESSURE VARIABILITY: There is evidence to suggest that end-organ damage is more frequent and more marked in hypertensives with greater 24 h blood pressure variability. It appears that antihypertensive treatment does not easily reduce this variability, although the intermittent measurements taken by automatic monitoring devices do not fully reflect patterns of blood pressure variation. It may be that hypertensives with a greater degree of blood pressure variability can obtain a reduction in the magnitude of this variability with antihypertensive treatment.

Antihypertensive Agents↗
PubMed1995

Calculation of trough:peak ratio of antihypertensive treatment from ambulatory blood pressure: methodological aspects.

OBJECTIVE: To address several methodological questions related to calculation of trough:peak ratio from 24 h ambulatory blood pressure (BP) recordings. METHODS: Data from patients with mild essential hypertension who were included in parallel group (n = 280) or cross-over studies (n = 39) were pooled. 24 h ambulatory BP recordings were available after 2- to 4-week washout from treatment and at the end of a 4- to 8-week period of treatment with calcium antagonists (n = 143), angiotensin converting enzyme inhibitors (n = 103) or placebo (73 patients from parallel group studies and 39 from a cross-over study). Each recording started between 0900 and 1000 h, immediately after the drug or placebo intake during the treatment phase. BP was measured at 15 min intervals during the day and at 15-20 min intervals during the night. Peak changes were calculated from systolic BP and diastolic BP 2-8 h after drug intake, and trough changes from readings taken during the last 4 h of the 24 h. RESULTS: Peak changes induced by drug treatment were progressively reduced when data were averaged over 1, 2, 4 and 6 h. BP reproducibility showed a concomitant increase and the best compromise between correct estimate of peak changes and reproducibility was the average of the adjacent 2 h with the maximal BP fall. Peak and trough (average of last 2 h) changes showed a normal distribution, whereas trough:peak ratios showed non-normal distributions, large scatters and many individual values with no pharmacodynamic significance (namely, much above unity and below zero). Selecting responders to treatment reduced the dispersion and made the trough:peak ratio distribution normal. There was no correlation between trough:peak ratios and changes in BP variability (standard deviation of 24 h mean) induced by treatment. Placebo administration caused no trough but a modest peak fall. Peak changes during placebo also showed a wide scatter and a non-normal distribution, which makes correction with respect to average peak placebo data inappropriate in parallel-group studies. However, placebo correction may be performed for each subject in cross-over studies, leading to a reduction in peak changes and an increase in trough:peak ratio values. CONCLUSIONS: When the trough:peak ratio is assessed from ambulatory BP, peak and trough changes should preferably be computed over a 2 h time window. To remove values with no pharmacodynamic significance, the analysis should preferably be conducted only in responders to treatment at peak. Although placebo is accompanied by some peak effect, placebo correction might be appropriate only for individual subjects in cross-over studies.

Antihypertensive Agents↗
PubMed1995

Blood pressure variability, cardiovascular risk and antihypertensive treatment.

TWENTY-FOUR HOUR BLOOD PRESSURE PARAMETERS: The use of ambulatory blood pressure monitoring techniques has shown clearly that 24-h average blood pressure is more closely related to the end-organ damage of hypertension than isolated office blood pressure readings. It has also provided evidence that the degree of blood pressure variability over a 24-h period may be independently related to the cardiovascular complications of hypertension. However, all the available data on this issue come from cross-sectional studies, and prospective evidence on the actual prognostic value of 24-h blood pressure parameters has only recently been provided for daytime blood pressure variability. There is still no prospective evidence concerning overall 24-h blood pressure variability. ANTIHYPERTENSIVE AGENTS AND BLOOD PRESSURE VARIABILITY: Available antihypertensive agents are unable to effectively buffer blood pressure variability. However, drugs with a long-lasting antihypertensive effect and an optimal trough: peak ratio may at least prevent further iatrogenic increases in the amplitude of blood pressure fluctuations. BEAT-TO-BEAT BLOOD PRESSURE MONITORING: The ability of antihypertensive agents to actually reduce 24-h blood pressure variability needs to be demonstrated in future studies, using beat-to-beat blood pressure monitoring which is now possible by means of non-invasive techniques.

Antihypertensive Agents↗
PubMed1995

Blood pressure variability over 24 hours: its different components and its relationship to the arterial baroreflex.

This paper describes several different methods for the analysis of blood pressure and heart rate variability over the 24 hours, both in the time and in the frequency domain. The mechanisms possibly involved in the genesis of the variations in blood pressure and heart rate which occur over a 24-hour period are also discussed. Finally, new approaches to the dynamic evaluation of the sensitivity of baroreflex control of heart rate and of its changes over the 24 hours in daily life conditions, based on computer analysis of the interaction between fluctuations in blood pressure and heart rate, are described. Data obtained by applying these methods in different clinical conditions (normotensive vs. hypertensive subjects, young vs. elderly individuals and pure autonomic failure patients) are presented.

Journal Article↗
PubMed1995

Effects of aging on 24-h dynamic baroreceptor control of heart rate in ambulant subjects.

The effects of aging on the dynamic modulation of baroreflex sensitivity over 24 h was assessed in eight elderly (mean age +/- SD, 63.9 +/- 3.2 yr) and in eight young (23.9 +/- 6.1 yr) mild or moderate essential hypertensive patients, who were subject to a 24-h intra-arterial (Oxford technique) blood pressure recording in ambulatory conditions. The sensitivity of baroreflex control of the heart rate was dynamically assessed by quantifying 1) the slope of the regression line between pulse interval (the reciprocal of heart rate) and systolic blood pressure changes over spontaneously occurring hypertension-bradycardia or hypotension-tachycardia sequences (time domain analysis) and 2) the ratio between spectral-powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha-coefficient: frequency domain analysis). The 24-h average sequence slope was lower in old than in young individuals (4.4 +/- 0.5 vs. 9.9 +/- 1.3 and 4.8 +/- 0.7 vs. 8.4 +/- 1.4 ms/mmHg for hypertension-bradycardia and hypotension-tachycardia sequences, respectively; P < 0.05 for both). Similar results were obtained by using the alpha-coefficient approach. The marked nighttime increase in baroreflex sensitivity observed in young individuals was much less evident in the elderly. Thus 24-h baroreflex sensitivity is markedly impaired by aging. The impairment becomes manifest also as an inability to increase baroreflex sensitivity at night.

Aged↗
PubMed1995

Sympathetic activation in obese normotensive subjects.

Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2, mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7 +/- 1.3 bursts per minute), the difference being highly statistically significant (P < .02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity.

Adult↗