Showing papers by "Giuseppe Mancia published in 2000"

Ambulatory Blood Pressure Monitoring and Organ Damage

Abstract: Several papers have suggested that 24-hour average blood pressure (BP) is superior to office BP in relation to hypertension target organ damage. This review article will specifically address the evidence provided in this regard by either cross-sectional or longitudinal studies. It will also critically discuss the available data supporting the concept that not only 24-hour average BP values, but also specific BP patterns occurring within the 24 hours may have clinical relevance. This is the case for daytime versus nighttime BP, the day/night BP difference, the morning BP rise, and overall BP variability.

Adrenergic and Reflex Abnormalities in Obesity-Related Hypertension

Abstract: Previous studies have shown that essential hypertension and obesity are both characterized by sympathetic activation coupled with a baroreflex impairment. The present study was aimed at determining the effects of the concomitant presence of the 2 above-mentioned conditions on sympathetic activity as well as on baroreflex cardiovascular control. In 14 normotensive lean subjects (aged 33. 5+/-2.2 years, body mass index 22.8+/-0.7 kg/m(2) [mean+/-SEM]), 16 normotensive obese subjects (body mass index 37.2+/-1.3 kg/m(2)), 13 lean hypertensive subjects (body mass index 24.0+/-0.8 kg/m(2)), and 16 obese hypertensive subjects (body mass index 37.5+/-1.3 kg/m(2)), all age-matched, we measured beat-to-beat arterial blood pressure (by Finapres device), heart rate (HR, by ECG), and postganglionic muscle sympathetic nerve activity (MSNA, by microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Blood pressure values were higher in lean hypertensive and obese hypertensive subjects than in normotensive lean and obese subjects. MSNA was significantly (P:<0.01) greater in obese normotensive subjects (49.1+/-3.0 bursts per 100 heart beats) and in lean hypertensive subjects (44.5+/-3.3 bursts per 100 heart beats) than in lean normotensive control subjects (32.2+/-2.5 bursts per 100 heart beats); a further increase was detectable in individuals with the concomitant presence of obesity and hypertension (62.1+/-3. 4 bursts per 100 heart beats). Furthermore, whereas in lean hypertensive subjects, only baroreflex control of HR was impaired, in obese normotensive subjects, both HR and MSNA baroreflex changes were attenuated, with a further attenuation being observed in obese hypertensive patients. Thus, the association between obesity and hypertension triggers a sympathetic activation and an impairment in baroreflex cardiovascular control that are greater in magnitude than those found in either of the above-mentioned abnormal conditions alone.

Mechanisms and clinical implications of blood pressure variability

Abstract: Several studies have unequivocally shown that the target-organ damage associated with the hypertensive condition is more closely related to 24 h average blood pressure values than to clinic blood pressure. Blood pressure, however, is highly variable over the daytime and night-time period, and of major interest is whether average 24 h blood pressure values, as well as 24 h blood pressure variability, correlate with, and are possibly responsible for, the hypertension-related alterations of the target-organ structure and function. This paper will address this issue by discussing the main features of blood pressure variability in hypertension. It will also examine the mechanisms involved in this phenomenon, with particular emphasis on the pathogenetic role of sympathetic neural factors. The clinical relevance of blood pressure variability in promoting target-organ damage, as well as its therapeutic implications, will finally be highlighted.

Sympathetic and reflex alterations in systo-diastolic and systolic hypertension of the elderly.

Abstract: BACKGROUND Previous studies have shown that young and middle-aged essential hypertensives are characterized by a sympathetic activation coupled with an impaired baroreflex-heart rate control. The present study aimed to determine whether these neuroadrenergic and reflex alterations also characterize systo-diastolic and systolic hypertension of the elderly. SUBJECTS AND METHODS In 20 untreated elderly essential hypertensive subjects [10 with a systo-diastolic and 10 with an isolated systolic hypertension, aged 67.2 +/- 1.5 years and 66.9 +/- 1.7 years (mean +/- SEM)], we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 11 age-matched normotensive control subjects. RESULTS Compared to the elderly normotensive group, muscle sympathetic nerve activity was increased to a similar degree in the group of systo-diastolic and systolic hypertension (50.8 +/- 4.2 versus 75.2 +/- 5.2 and 70.4 +/- 5.1 bursts per 100 heart beats, respectively, P< 0.01 for both). In the control group, the stepwise increase in arterial pressure induced by phenylephrine caused progressive bradycardia and sympathoinhibition, while the stepwise decrease in arterial pressure had opposite effects. While baroreceptor-heart rate control was markedly impaired (average reduction 41.6%), in both systo-diastolic and systolic hypertensive patients, baroreceptor modulation of sympathetic nerve traffic was similar to that seen in normotensive individuals. CONCLUSIONS These data demonstrate that sympathetic activation is not only a feature of young and middle-aged, but also of elderly hypertensives, regardless of whether both systolic and diastolic or only systolic blood pressure is increased. They also show that hypertension of the elderly is not accompanied by an impaired baroreceptor modulation of sympathetic nerve traffic.

Attenuation of the “White-Coat Effect” by Antihypertensive Treatment and Regression of Target Organ Damage

Abstract: —This study assessed whether 2 common surrogate measures of the “white-coat effect,” namely the clinic-daytime and the clinic-home differences in blood pressure (BP), were attenuated by long-term antihypertensive treatment and whether this attenuation is relevant to the treatment-induced regression of left ventricular hypertrophy, thus having clinical significance. We considered data from 206 patients with essential hypertension (aged 20 to 65 years) who had a diastolic BP between 95 and 115 mm Hg and echocardiographic evidence of left ventricular hypertrophy. In each patient, clinic BP, 24-hour ambulatory BP, and left ventricular mass index were assessed at baseline, after 3 and 12 months of treatment with an angiotensin-converting enzyme inhibitor, and after a final 4-week placebo run-off period. At baseline, the clinic-daytime differences in systolic and diastolic BP were 12.1±15.4 and 6.8±10.1 mm Hg, respectively; the corresponding values for the clinic-home differences were 5.7±10.6 and 2.9±6.1 mm Hg, respectively. These differences were reduced by 57.6% and 77.1% ( P P

Lacidipine and blood pressure variability in diabetic hypertensive patients

Abstract: The aim of our study was to assess the effects of lacidipine, a long-acting calcium antagonist, on 24-hour average blood pressure, blood pressure variability, and baroreflex sensitivity. In 10 mildly to moderately hypertensive patients with type II diabetes mellitus (aged 18 to 65 years), 24-hour ambulatory blood pressure was continuously monitored noninvasively (Portapres device) after a 3-week pretreatment with placebo and a subsequent 4-week once daily lacidipine (4 mg) or placebo treatment (double-blind crossover design). Systolic blood pressure, diastolic blood pressure, and heart rate means were computed each hour for 24 hours (day and night) at the end of each treatment period. Similar assessments were also made for blood pressure and heart rate variability (standard deviation and variation coefficient) and for 24-hour baroreflex sensitivity, which was quantified (1) in the time domain by the slope of the spontaneous sequences characterized by progressive increases or reductions of systolic blood pressure and RR interval and (2) in the frequency domain by the squared ratio of RR interval and systolic blood pressure spectral power approximately 0.1 and 0.3 Hz over the 24 hours. Compared with placebo, lacidipine reduced the 24-hour, daytime, and nighttime systolic and diastolic blood pressure (P<0.05) with no significant change in heart rate. It also reduced 24-hour, daytime, and nighttime standard deviation (-19.6%, -14.4%, and -24.0%, respectively; P<0.05) and their variation coefficient. The 24-hour average slope of all sequences (7.7+/-1.7 ms/mm Hg) seen during placebo was significantly increased by lacidipine (8.7+/-1.8 ms/mm Hg, P<0.01), with a significant increase being obtained also for the 24-hour average alpha coefficient at 0.1 Hz (from 5.7+/-1.5 to 6.4+/-1.3 ms/mm Hg, P<0.01). Thus, in diabetic hypertensive patients, lacidipine reduced not only 24-hour blood pressure means but also blood pressure variability. This reduction was accompanied by an improvement of baroreflex sensitivity. Computer analysis of beat-to-beat 24-hour noninvasive blood pressure monitoring may offer valuable information about the effects of antihypertensive drugs on hemodynamic and autonomic parameters in daily life.

The sympathetic nervous system in human hypertension.

Abstract: 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.

The importance of blood pressure variability in hypertension.

Abstract: Use of ambulatory blood pressure monitoring (ABPM) techniques has revealed that blood pressure is characterized by a considerable degree of variability over a 24 h period as a result, not only of the well-known fluctuations that occur between wakefulness and sleep, but also of the minute-to-minute changes induced by a variety of behavioural conditions. The degree of these variations is also influenced by neural mechanisms responsible for cardiovascular regulation, such as the arterial baroreflex. Blood pressure variability increases with age and blood pressure values, and its magnitude has been shown to correlate independently with the target-organ damage of hypertension. This has stimulated both the development of antihypertensive drugs able to reduce blood pressure homogeneously over 24 h, and recent proposals to develop more accurate indices, such as the smoothness index, to quantify the distribution of the antihypertensive effect over the entire day and night. Despite the important information that ABPM can provide concerning daily-life blood pressure variations and their modification by treatment, international guidelines suggest that it should not yet be used routinely in daily practice, but rather reserved for selected patients.

Depression during interferon therapy for chronic viral hepatitis: early identification of patients at risk by means of a computerized test.

Abstract: Objectives At the doses used for the treatment of chronic viral hepatitis, interferon (IFN)-related side-effects are usually modest, even though in some cases they require the interruption of therapy. Neuropsychiatric disturbances that range from modest depression and irritability to forms of manic-depressive psychosis and attempted or successful suicides are among the most important side-effects. The aim of our study was to determine whether the Minnesota Multiphasic Personality Inventory (MMPI) is a sensitive and reliable test for the early identification of patients at risk of depression before IFN therapy is commenced, and whether it could be useful for the monitoring of these patients during treatment. Methods We prospectively studied 67 patients with chronic active liver diseases, consecutively enrolled in open studies and treated with r-IFNα2. Before starting therapy and after 3 months of treatment, all patients underwent a clinical neurological evaluation and MMPI. Results At baseline, the correlation between the clinical evaluation and the score of the depression scale of the MMPI was statistically significant (P< 0.0001). Nine of 14 (64.3%) patients with a baseline score ≥ 60/100 showed a depressive mood after 3 months of therapy. Five of 44 patients (11.3%) with a baseline score < 60/100 showed a depression of medium level after 3 months of treatment This difference was highly significant (P< 0.0001). Conclusions According to our results, the MMPI is a reliable and sensitive test for the early identification of patients at risk of depression before and during IFN therapy for chronic viral liver diseases.

Modulation of Sympathetic Coronary Vasoconstriction by Cardiac Renin-Angiotensin System in Human Coronary Heart Disease

Abstract: Background—In humans, angiotensin II enhances the sympathetic coronary vasoconstriction elicited by the cold pressor test (CPT) and diving. Whether this enhancement depends on the circulating angiotensin II or on the locally produced angiotensin II is unknown, however. Methods and Results—We addressed this issue in 14 patients with severe coronary artery disease by evaluating the effects of a 2-minute CPT (n=14) and a 30-second dive (n=8) on mean arterial pressure (MAP, arterial catheter), heart rate (ECG), coronary sinus blood flow (CBF, thermodilution technique), and coronary vascular resistance (MAP/CBF ratio). The 2 stimuli were applied at the end of left intracoronary infusion of either saline or benazeprilat diluted at the concentration of 25 μg/mL. The rate of benazeprilat infusion had been preliminarily demonstrated to reduce angiotensin II concentration in the coronary sinus without affecting its arterial concentration. The changes in MAP and heart rate induced by CPT and diving were superimposab...

Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients.

Abstract: Recent studies showed that in diabetic hypertensive patients, administration of angiotensin-converting enzyme (ACE)-inhibitors or calcium antagonists can effectively lower blood pressure (BP) and prevent diabetes-related cardiovascular complications with no adverse metabolic effects. We sought to assess the antihypertensive and metabolic effects of the new dihydropyridine calcium antagonist manidipine (M) in patients with diabetes mellitus and essential hypertension as compared with the ACE inhibitor enalapril (E). After 3 weeks of placebo, 101 (62 men; age range, 34-72 years) hypertensives with type II diabetes mellitus were randomized to M 10-20 mg or E 10-20 mg, od, for 24 weeks. At the end of the placebo period and the active-treatment phase, BP was measured with a mercury sphygmomanometer (office, O) and over the 24 h by ambulatory (A) monitoring. ABP recordings were analyzed to obtain 24-h, day (6 a.m. to midnight), and night (midnight to 6 a.m.) average systolic (S) and diastolic (D) BP and heart rate (HR) values. Homogeneity of the antihypertensive effect over the 24 h was assessed by the smoothness index [SI: i.e., the ratio between the average of the 24 hourly BP changes after treatment and the corresponding standard deviation (the higher the SI, the more uniform is the BP control by treatment over the 24 h]. The O SBP and DBP were significantly (p < 0.01) and similarly reduced by M (16 +/- 10 and 13 +/- 6 mm Hg, n = 49) and E (15 +/- 10 and 13 +/- 6 mm Hg, n = 45). The percentage of patients whose O DBP was reduced < or = 85 mm Hg (i.e., the value indicated to be the optimal DBP goal in diabetic hypertensives) was similar for M (37%) and E (40%). The reduction of 24-h BP also was similar between M (n = 38) and E (n = 38) for both drugs (systolic, 6 +/- 11 and 8 +/- 10 mm Hg; diastolic, 5 +/- 8 and 5 +/- 7; NS, M vs. E). The antihypertensive effect was distributed in a similar homogeneous fashion throughout the dosing interval, as shown by the similar SI values (M, 0.6 +/- 1.2 for SBP and 0.6 +/- 0.9 for DBP; E, 0.6 +/- 0.8 for SBP and 0.5 +/- 0.7 for DBP; NS, M vs. E). O and A HR were unchanged by either treatment. Markers of glucose and lipid metabolism and renal function were not significantly modified by treatment both with M and with E. In the diabetic hypertensives, M was as effective and metabolically neutral as the ACE-inhibitor E.

The Role of Ambulatory Blood Pressure Monitoring in Elderly Hypertensive Patients

Abstract: There is strong evidence that ambulatory blood pressure measurements show only limited agreement with blood pressures measured in the clinic ('office( blood pressures), and are more relevant to the prognosis of hypertension. Several markers of end-organ damage, for example, have been shown to correlate more strongly with 24-h blood pressure than with office blood pressure. In addition, end-organ damage has been shown to be correlated with 24-h blood pressure variability. Ambulatory blood pressure monitoring (ABPM) has revealed a number of differences between the blood pressure profiles of elderly and younger patients. Since 24-h blood pressure control is now widely accepted as an important goal of antihypertensive therapy, ABPM has a potentially useful role in monitoring treatment in clinical trials in elderly patients.

Clinical benefits of consistent reduction in the daily blood pressure of hypertensive patients.

Abstract: Mean 24-hour blood pressure (BP) values are more closely associated with cardiovascular events and target organ damage than are clinic measurements, and therefore may be more useful for assessing drug efficacy. Clinically important information may also be contained in other data derived from ambulatory BP measurement. For example, both daytime and nighttime BPs are correlated with organ damage and cardiovascular events. BP variability is also correlated with organ damage and events. This observation is important because BP variability may differ greatly among individuals and may increase markedly in hypertension. A large increase in BP variability may also occur with some antihypertensive drugs, particularly those whose efficacy declines as they are metabolized. The most important aim of antihypertensive therapy should be the dynamic control of BP-lower BP and lower BP variability.

24 H Ambulatory Blood Pressure Variability and Carotid Artery Damage: Baseline Data from the Elsa Study.

Abstract: 38 Aim of our study was to evaluate the relationship of carotid intima-media thickness (IMT) with clinic (C) and 24 h ambulatory blood pressure (ABP) and with 24 h BP variability (V), from baseline data of the European Lacidipine Study on Atherosclerosis (ELSA). Design and Methods: In 1663 hypertensive patients in washout from treatment (56.2± 7.6 years; 54.4% males) several measures of maximum IMT were obtained from up to 12 different carotid sites by intensively trained and repeatedly certified sonographers. CBP was the average of 3 sitting measurements. From ABP recordings (Spacelabs 90207 or Takeda TM2021) we obtained: 1) 24 h, day and night average SBP and DBP, 2) day-night SBP and DBP differences of means ( -Δ), 3) 24h, day and night SBP and DBP standard deviations (SD, measure of BPV).Similar calculations were done for PP and HR. The influence of ABP and C variables on IMT was investigated by univariate and multiple regression analyses. Results: In the univariate analysis IMT was not related to C or 24h DBP, but was significantly related to C SBP (r from 0.16 to 0.21; p

The role of angiotensin II receptor antagonists in hypertension management: focus on candesartan cilexetil.

Abstract: The prevention and treatment of hypertension both from the viewpoint of individual patient care and in terms of population health presents a considerable challenge to the medical profession. To assist in meeting this challenge, various bodies have produced guidelines for the management of hypertension during the past 30 years. The aim of this article is to review the recommendations of the most recent of these - the 1999 WHO-ISH guidelines - as well as previous similar documents, including the earlier 1993 WHO-ISH guidelines and the US Joint National Committee on prevention, detection, evaluation

European Society of Hypertension: a note from the President

Abstract: The European Society of Hypertension (ESH) has decided to hold its meetings on an annual rather than a biannual basis. The decision has also been taken to keep Milan as the venue of the meetings held in uneven years (2001, 2003 and 2005) while electing different European cities as the venues of meetings held in even years: GoÈteborg in 2000; Prague in 2002 (in conjunction with the meeting of the International Society of Hypertension); Paris in 2004; and Madrid in 2006.

Applying evidence-based medicine to current practice: a round table panel discussion.

Abstract: Over the past decade, an expanding body of epidemiological and clinical trial data has been collated, culminating in the development of guidelines designed to help physicians make decisions about intervention and the intensity of treatment, based on objective assessments of the overall level of risk for cardiovascular disease. However, guidelines are not prescriptive and allow physicians leeway in interpretation. Thus, it is of clinical interest to explore some of the issues that may influence the use of these guidelines in clinical practice. This paper summarises a round table panel discussion that highlighted the usefulness of current guidelines, but also demonstrated that these guidelines, and the evaluation of cardiovascular risk, need to be used with care and always interpreted in the light of sound clinical judgement.