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Biomedical subjects

G Mancia

Publications and source records attributed to G Mancia.

At least 73 records · Page 4Linked to original sources

Mechanisms and clinical implications of blood pressure variability.

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.

Animals↗

Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients.

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.

Adult↗

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

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-IFNalpha2. 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 > or = 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.

Adult↗

The importance of blood pressure variability in hypertension.

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.

Antihypertensive Agents↗

Attenuation of the "white-coat effect" by antihypertensive treatment and regression of target organ damage.

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<0.01) and by 65.7% and 64.3% (P<0.01), respectively, after 12 months of treatment, with a partial return toward the pretreatment differences after the final placebo period. The observed treatment-induced reductions in left ventricular mass index and those in the clinic-daytime or clinic-home differences for systolic and diastolic BP showed no significant relationship when tested by multiple regression analysis. This provides the first longitudinal evidence that clinic-daytime and clinic-home differences in BP have no substantial value in predicting the regression of target organ damage, such as left ventricular hypertrophy, that has prognostic relevance.

Adult↗

Influence of diabetes and type of hypertension on response to antihypertensive treatment.

The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension (diastolic or isolated systolic) influences blood pressure (BP) response to treatment. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years. Dynamic randomization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors. Patients with isolated systolic hypertension were also separately randomized. Atenolol or enalapril was the mandatory second-line drug. In 5669 patients who completed the 18-week titration, BP fell from 172+/-15/99+/-9 mm Hg (mean+/-SD) while receiving placebo to 139+/-12/82+/-7 mm Hg. Twenty-six percent of patients required 2 drugs, and 4% required 3 drugs. Patients with diabetes were the most resistant to treatment, requiring second and third drugs 40% and 100% more frequently than patients without diabetes and achieving marginally the highest final BP, for any risk group, of 141+/-13/82+/-8 mm Hg. Age, smoking, gender, hypercholesterolemia, left ventricular hypertrophy, and existing atherosclerosis had little (<1 mm Hg) or no influence on BP at the end of titration, but all except smoking slightly reduced the initial response of either systolic or diastolic BP. Patients with isolated systolic hypertension were slightly more responsive than average to treatment. Our findings suggest that in patients at high absolute risk of cardiovascular complications from hypertension, the risk factors themselves do not prevent the recommended BP targets from being achieved.

Aged↗

Adrenergic and reflex abnormalities in obesity-related hypertension.

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.

Adrenergic Fibers↗

Lacidipine and blood pressure variability in diabetic hypertensive patients.

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.

Antihypertensive Agents↗

Ambulatory blood pressure monitoring and organ damage.

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.

Blood Pressure↗

How to measure baroreflex sensitivity: from the cardiovascular laboratory to daily life.

Arterial baroreflex function in humans is commonly assessed through a number of laboratory tests based on quantification of the reflex responses in heart rate or blood pressure to external stimuli applied to the cardiovascular system. Evidence is available that these laboratory estimates of baroreflex sensitivity have both pathophysiological and clinical relevance. Indeed, a number of studies have shown that the sensitivity of the baroreceptor-heart rate reflex may have a prognostic value in myocardial infarction, heart failure and diabetic patients, where mortality seems to be inversely related to the sensitivity of cardiac baroreflex modulation. A deeper insight into the features of daily-life baroreflex cardiovascular control has been offered more recently by techniques based on computer analysis of spontaneous blood pressure and heart rate fluctuations. This innovative approach allows spontaneous baroreflex sensitivity to be assessed in real life conditions, with no need for external stimulation of the patient as required by the older laboratory techniques. This review will briefly survey the methods most widely used to assess baroreflex function in humans, in the laboratory and in daily life.

Baroreflex↗

The role of ambulatory blood pressure monitoring in elderly hypertensive patients.

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.

Aged↗

Comparison of angiotensin II receptor blockers: impact of missed doses of candesartan cilexetil and losartan in systemic hypertension.

Blood pressure remains poorly controlled in the hypertensive population due in large part to low or unsatisfactory patient compliance. Clinical studies that incorporate an intentionally missed dose have been designed to evaluate the impact of poor patient compliance on the effectiveness of antihypertensive medications. In these studies, ambulatory blood pressure monitoring is continued throughout the dosing interval and beyond in order to determine when systolic and diastolic blood pressure increase into the hypertensive range. In an 8-week, randomized, double-blind, placebo-controlled trial in patients with mild-to-moderate hypertension, the antihypertensive effects of candesartan cilexetil 16 mg were maintained after a missed dose, whereas systolic and diastolic blood pressure increased toward baseline levels after a missed dose of losartan 100 mg. Candesartan cilexetil provided a significantly greater reduction in sitting systolic (p = 0.004) and diastolic blood pressure (p = 0.008) than losartan when measured 48 hours after the last dose. Moreover, the homogeneity of antihypertensive effects was greater after candesartan cilexetil than losartan based on calculation of the smoothness index from ambulatory systolic and diastolic measurements during the first 24-hour period after dosing and during the 12-hour period after the missed dose. These results demonstrate that missing or delaying a dose of candesartan cilexetil has less impact on antihypertensive efficacy than missing or delaying a dose of losartan.

Adult↗

Baroreflex and non-baroreflex modulation of vagal cardiac control after myocardial infarction.

Vagal control of sinus node exerted by arterial baroreceptors is markedly impaired 48 hours after acute myocardial infarction (AMI), but it recovers 10 days later. However, it is unknown whether this recovery is peculiar to baroreceptor vagal control or reflects normalization of the overall vagal modulation of heart rate. In 21 untreated patients (aged 51+/-3 years, mean +/- SEM) studied 10+/-1 and 21+/-1 days after an AMI and in 13 healthy controls (aged 47+/-2 years), we examined the increases in RR interval (electrocardiogram) induced by carotid baroreceptor stimulation via a neck chamber and by immersion of the face in iced water for 15 seconds (diving reflex). Both 10 and 21 days after AMI, baseline blood pressure and RR interval values were superimposable to those obtained in controls. Ten days after AMI, the bradycardic responses to carotid baroreceptor stimulation were similar to those seen in controls (maximal RR interval lengthenings: 248+/-34 vs 270+/-31 ms, respectively, p = NS) and remained virtually unchanged later. In contrast, the bradycardic response to diving was reduced in patients after AMI compared with controls (maximal RR interval lengthenings: 203+/-43 vs 325+/-52 ms, respectively, p <0.05) and did not improve later. Thus, in AMI recovery of the early impairment of baroreceptor-heart rate control does not reflect normalization of vagal cardiac control, which remains lower than normal values at a time when the baroreflex is restored.

Blood Pressure↗

Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

CONTEXT: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies. OBJECTIVE: To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension. DESIGN: Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique. SETTING: Family practices and outpatient clinics at primary and secondary referral hospitals. PARTICIPANTS: A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic. INTERVENTIONS: For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393). MAIN OUTCOME MEASURES: Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points. RESULTS: After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement. CONCLUSIONS: In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.

Aged↗