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Biomedical subjects

G Mancia

Publications and source records attributed to G Mancia.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. A critical appraisal.

Blood pressure variability includes rhythmic and nonrhythmic fluctuations that, with the use of spectral analysis, appear as clear peaks or broadband power, respectively. This review offers a concise and critical description of the spectral methods most commonly used (fast Fourier transform versus autoregressive modeling, time-varying versus broadband spectral analysis) and an evaluation of their advantages and disadvantages. It also provides insight into the problems that still affect the physiological and clinical interpretations of data provided by spectral analysis of blood pressure and heart rate variability. In particular, the assessment of blood pressure and heart rate spectra aimed at providing indexes of autonomic cardiovascular modulation is discussed. Evidence is given that multivariate models--which allow evaluation of the interactions between changes in blood pressure, heart rate, and other biological signals (such as respiratory activity) in the time or frequency domains--offer a more comprehensive approach to the assessment of cardiovascular regulation than that represented by the separate analysis of fluctuations in blood pressure or heart rate only.

Autonomic Nervous System

Sympathectomy and cardiovascular spectral components in conscious normotensive rats.

We examined the extent to which sympathetic influences are reflected by spectral powers of blood pressure and pulse interval in specific frequency bands in spontaneously behaving Wistar-Kyoto rats subjected to continuous intraarterial blood pressure recording. The rats were pretreated with 6-hydroxydopamine (150 mg/kg twice in 1 week, n = 19) to produce chemical sympathectomy or received vehicle (n = 15). In the sympathectomized group, additional monitoring sessions were performed with rats under alpha-adrenergic receptor blockade with phenoxybenzamine (n = 8), beta-receptor blockade with propranolol (n = 7), or cholinergic receptor blockade with atropine (n = 8). Blood pressure signals were analyzed by a computer to calculate spectral powers (fast Fourier transform) in the low-frequency (0.025 to 0.1 Hz), mid-frequency (0.1 to 0.6 Hz), and high-frequency (0.8 to 3.0 Hz) bands. In sympathectomized rats, low-frequency power of blood pressure was 70% greater than in intact rats, whereas mid-frequency power was 60% smaller (P < .05 for both) and high-frequency power was unchanged. High-frequency power of pulse interval was also unchanged in sympathectomized rats, whereas low- and mid-frequency powers were reduced by approximately 50% (P < .05). No further alterations in spectral powers were observed by adding alpha- or beta-adrenergic blockade to sympathectomy, whereas adding cholinergic blockade caused a striking reduction in all pulse interval powers. Thus, mid-frequency blood pressure power depends on sympathetic but also to a substantial extent on nonsympathetic influences. Sympathetic influences do not contribute to low-frequency blood pressure power, having instead a restraining effect. The low- and mid-frequency pulse interval powers depend on both sympathetic and vagal influences. Thus, no blood pressure or pulse interval power in the mid- and low-frequency ranges can be regarded as a specific marker of sympathetic activity.

Adrenergic alpha-Antagonists

Sympathetic modulation of radial artery compliance in congestive heart failure.

Animal studies have suggested that arterial compliance can be modulated by adrenergic influences. Whether this adrenergic modulation also occurs in humans is still a matter of debate. In the present article we address this issue by examining the relationships between sympathetic tone and arterial compliance in a variety of physiological and pathophysiological conditions. We have found that cigarette smoking, ie, an action that produces a marked sympathetic activation, causes a significant reduction in radial artery compliance, as measured by an echotracking device capable of providing continuous beat-to-beat evaluation of this hemodynamic variable. When expressed as compliance index, ie, as the ratio between the area under the compliance-pressure curve and pulse pressure, the reduction amounted to 35.7 +/- 4.8% (mean +/- SEM) and was independent of the smoking-related blood pressure increase. Furthermore, pharmacological stimulation of adrenergic receptors located in the arterial wall was also shown to affect arterial compliance because the radial artery compliance index was markedly reduced (- 29.5 +/- 3.9%) during phenylephrine infusion in the brachial artery at doses devoid of any systemic blood pressure effect. Evidence was also obtained that the relationship between sympathetic activation and arterial compliance has pathophysiological relevance, because in 17 patients with congestive heart failure (New York Heart Association classes II through IV) there was a significant inverse correlation (r = .62, P < .01) between muscle sympathetic nerve activity (directly measured by microneurography in the peroneal nerve) and radial artery compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Angiotensin-converting enzyme inhibition and radial artery compliance in patients with congestive heart failure.

Congestive heart failure is characterized by a clear-cut impairment of arterial compliance of medium-sized arteries, but whether this alteration is irreversible or can be favorably affected by cardiovascular drugs currently used in congestive heart failure treatment is unknown. We studied 9 congestive heart failure patients (New York Heart Association class II; age, [mean +/- SEM] 60.7 +/- 3.3 years) receiving diuretic and digitalis treatment in whom arterial compliance was assessed at the level of the radial artery by an echotracking device capable of measuring the arterial diameter along the entire cardiac cycle. Beat-to-beat arterial blood pressure was concomitantly measured by a Finapres device that allowed diameter-pressure curves and compliance-pressure curves (Langewouters' formula) to be calculated for the entire systolic-diastolic blood pressure range. Arterial compliance was expressed as the area under the compliance-pressure curve normalized for pulse pressure (compliance index). Data were collected before and after 4 and 8 weeks of oral administration of benazepril (10 mg/day). Ten healthy subjects were studied before and after an observational period of 4 weeks (5 subjects) or 8 weeks (5 subjects), and 9 age-matched mildly essential hypertensive subjects studied before and after 4 to 12 weeks of benazepril administration served as control subjects. In congestive heart failure patients, baseline compliance index was significantly less than in normotensive and hypertensive subjects. However, the compliance index showed a marked increase after 4 weeks of benazepril administration (+95.7 +/- 24.9%, P < .05); the increase was also marked after 8 weeks of angiotensin-converting enzyme inhibitor treatment (+77.7 +/- 4.2%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Radial artery compliance in young, obese, normotensive subjects.

Obesity is characterized by a number of cardiovascular alterations, and whether these alterations involve arterial compliance is unknown. In 12 young, obese, normotensive subjects (age, 23.9 +/- 1.3 years; mean +/- SEM) and 12 age- and sex-matched lean control subjects we measured blood pressure, radial artery diameter, and radial artery compliance continuously over the systodiastolic pressure range with a Finapres device and recently developed echo-tracking device. Measurements were obtained at baseline and after prolonged ischemia, that is, when diameter and compliance are increased. Blood pressure values were normal in both groups (obese subjects: 109.2 +/- 4.9/68.2 +/- 2.7 mm Hg; lean control subjects: 108.2 +/- 4.1/60.7 +/- 3.8 mm Hg), but in addition to a marked increase in body mass index (38.5 +/- 0.8 versus 23.1 +/- 0.9 kg/m2, P < .01), obese subjects showed a slight and nonsignificant increase in heart rate (71.1 +/- 3.2 versus 66.7 +/- 3.3 beats per minute, P = NS), increases in left ventricular wall thickness and left ventricular mass index (121.5 +/- 4.8 versus 103.4 +/- 3.3 kg/m2, P < .01), no changes in plasma renin activity and plasma norepinephrine (compared with normal values), and a marked reduction in total body glucose uptake (glucose clamp technique). Obese subjects showed radial artery diameter and compliance values that were greater than those seen in control subjects throughout the systodiastolic pressure range. The differences were 13% (P < .05) and 96% (P < .01), respectively, and both diameter and compliance remained higher in obese than lean subjects after forearm ischemia. In obese and lean subjects baseline radial artery diameter values correlated highly with body weight, body surface area, and body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Blood pressure variability and its implications for antihypertensive therapy.

Although it is clear that antihypertensive treatment is beneficial in reducing stroke morbidity and mortality, the results of the major outcome studies show less impact on coronary heart disease. Studies utilizing 24-h blood pressure (BP) monitoring show a positive association between target organ damage and the level of 24-h BP, and with variability in BP, which is an independent determinant of target organ damage. Current understanding of the pathogenesis and pathophysiology of coronary heart disease suggests that optimal antihypertensive treatment should ensure the following: effective 24-h BP control, smooth antihypertensive effect with reduced variability; attenuation of the early morning surge in BP; maintenance of the normal circadian pattern of BP; effective therapeutic coverage in the face of suboptimal compliance; and lack of reflex activation of the sympathetic nervous system. On the basis of our current understanding, this optimum is most likely to be achieved by the use of antihypertensive agents with a long duration of action.

Antihypertensive Agents

Ambulatory blood pressure monitoring in the evaluation of antihypertensive treatment: additional information from a large data base.

Aims of our study were i) to compare in a large number of hypertensive subjects the relative effect of antihypertensive treatment on clinic (C) blood pressure (BP) and various ambulatory (A) BP components, and ii) to determine whether antihypertensive treatment affects BP variability. In 266 mild essential hypertensive outpatients (age: 18-78 years) CBP (trough measurements) and ABP (Spacelabs 90202 or 90207) were measured after 3 to 4 weeks of wash-out and after 4 to 8 weeks of treatment with an ACE-inhibitor (n = 135) or a calcium-antagonist (n = 131). ABP recordings were analyzed to obtain average 24 h, day-time (6 a.m. to midnight) and night-time (midnight to 6 a.m.) systolic and diastolic BP values and standard deviations (BP variabilities). Treatment reduced both CBP and ABP. Treatment-induced changes in CBP showed a poor correlation with those in 24h, day- and night-time BP (r never > 0.23) and the correlation was poor also when trough ABP (mean of last 2 h) was considered. Twenty-four hour, day- and night-time BP were similarly reduced by treatment with a direct relationship between the initial BP values and the subsequent BP falls. BP standard deviations were also reduced by treatment in relation to the pretreatment values but the overall reduction was small, limited to the day-time and proportional or less than proportional to the reduction in mean values, with no changes or an increase in variation coefficients. The effects of ACE-inhibitor and calcium-antagonist treatments were superimposable. Our results from a large data base show that antihypertensive treatment effectively reduces all ABP components. The reduction cannot be predicted by the concomitant fall in CBP but it relates to the initial ABP values. Treatment has a limited effect on BP variability, this being the case both for ACE-inhibitors and calcium-antagonists.

Adolescent

Improving the management of hypertension in clinical practice.

Antihypertensive therapy is unquestionably beneficial, but current management of hypertension does not reduce cardiovascular risk to normotensive levels. Treatment of the hypertensive patient may be improved by a number of measures. These include control of SBP as well as DBP, with reduction to < 140/90 mmHg. Treatment of concomitant diseases and of other risk factors is likely to be of benefit, as is 24 h control of BP. Variability of BP appears to influence clinical outcome, but it is unclear whether this can be reduced by treatment. Poor patient compliance with treatment instructions may be an important factor in disappointing therapeutic performance, but could be improved with less complex treatment regimens.

Antihypertensive Agents

Cardiac and vascular structural changes in normotensive subjects with parental hypertension.

OBJECTIVE: To evaluate whether a predisposition to hypertension is associated with early cardiac and vascular alterations. SUBJECTS: Twenty-five normotensive subjects with both parents hypertensive (group 1) and 28 age- and sex-matched control subjects with both parents normotensive (group 2). METHODS: In the two groups the measurements included: clinic blood pressure; left ventricular end-diastolic diameter, septal wall thickness and posterior wall thickness (by echocardiography); minimal forearm and calf vascular resistances (i.e. resistance assessed immediately after prolonged ischaemia, which depends on arteriolar wall thickness); and baseline and postischaemic radial artery compliance-pressure curves over the systolodiastolic pressure range (by echotracking device and finger blood pressure). RESULTS: Group 1 had a slightly higher clinic blood pressure, and septal and posterior wall thickness, than group 2. Minimal forearm vascular resistance was clearly greater in group 1 than in group 2, whereas minimal calf vascular resistance was not significantly different in the two groups. Radial artery compliance was also similar in the two groups. CONCLUSIONS: Parental predisposition to hypertension is accompanied by cardiac and arteriolar structural changes qualitatively similar to those found in hypertensive patients, although arteriolar structural changes do not involve all vascular beds. Arterial compliance is not altered in this condition. Vascular changes may be determined by mechanisms other than blood pressure elevation.

Adult

[Changes in the compliance of the radial artery in normotensive subjects with familial hypercholesterolemia].

BACKGROUND: Recent studies have shown that in normotensive hypercholesterolemic subjects endothelial dependent dilatation of arterioles is impaired. METHODS: We studied the effects of hypercholesterolemia on arterial compliance in normotensive subjects of both sexes, with a normal serum cholesterol (n = 8, total serum cholesterol = 209 +/- 7 mg/dl, means +/- SEM), an elevated serum cholesterol (n = 8, 285 +/- 8 mg/dl) and familial hypercholesterolemia (n = 8, 393 +/- 20 mg/dl). All subjects were normotensive and devoid of clinical and laboratory evidence of atherosclerotic lesions. The mean age of the 3 groups was 46.7 +/- 2.5, 51.5 +/- 2.9 and 49.8 +/- 2.9 years respectively. In hypercholesterolemic subjects use of hypolipidemic drugs was stopped 2 months before the study. Arterial compliance was measured from the radial artery by an echo-tracking device capable of providing radial artery diameter and, with the addition of a Finapres device, diameter/pressure and compliance/pressure curves continuously over the systolic-diastolic blood pressure range. RESULTS: Mean arterial pressure was similar in the three groups (84.5 +/- 6.1, 79.8 +/- 2.4 and 73.1 +/- 4.4 mm Hg). Arterial compliance was similar in normocholesterolemic and non familial hypercholesterolemic subjects but it was strikingly reduced (50%) in familial hypercholesterolemic subjects. The reduction was even more evident following prolonged local ischemia because while in the first two groups arterial compliance increased after ischemia, in familial hypercholesterolemia no increase occurred. CONCLUSIONS: Thus, familial hypercholesterolemia is accompanied by a striking CONCLUSIONS: Thus, familial hypercholesterolemia is accompanied by a striking reduction in radial artery compliance, i.e. a marked increase in arterial wall stiffness. This may increase the traumatic effect of blood pressure on the arterial wall, favouring atherosclerosis. The lack of compliance alterations in non familial hypercholesterolemia suggests that this hemodynamic disturbance either occurs when serum cholesterol is more markedly increased or it has a genetic origin.

Analysis of Variance