Showing papers by "Giuseppe Mancia published in 1999"

Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension.

Abstract: ContextThe clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies.ObjectiveTo compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension.DesignSubstudy 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.SettingFamily practices and outpatient clinics at primary and secondary referral hospitals.ParticipantsA total of 808 older (aged ≥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.InterventionsFor 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 MeasuresTotal and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points.ResultsAfter 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.ConclusionsIn untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.

Sympathetic Activation in the Pathogenesis of Hypertension and Progression of Organ Damage

Abstract: Although animal models of hypertension have clearly shown that high blood pressure is associated with and is probably caused by an increase in sympathetic cardiovascular influences, a similar demonstration in humans has been more difficult to obtain for methodological reasons. There is now evidence, however, of increased sympathetic activity in essential hypertension. This article will review this evidence by examining data showing that plasma norepinephrine is increased in essential hypertension and that this is also the case for systemic and regional norepinephrine spillover, as well as for the sympathetic nerve firing rate in the skeletal muscle nerve district. Evidence will also be provided that sympathetic activation is a peculiar feature of essential hypertension, particularly in its early stages, with secondary forms of high blood pressure not usually characterized by an increased central sympathetic outflow. Humoral, metabolic, reflex, and central mechanisms are likely to be the factors responsible for the adrenergic activation characterizing hypertension, which may also promote the development and progression of the cardiac and vascular alterations that lead to hypertension-related morbidity and mortality, independent of blood pressure values. This represents the rationale for considering sympathetic deactivation one of the major goals of antihypertensive treatment.

Blood Pressure Monitoring. Task force V: White-coat hypertension.

Abstract: TERMINOLOGY Two terms are in current use to describe patients whose blood pressures are high only in a medical setting (white-coat hypertension and isolated office or clinic hypertension). The term white-coat effect is also commonly used to describe the pressor response to the clinic setting. DEFINITIONS White-coat hypertension is generally defined as a persistently elevated clinic blood pressure in combination with a normal ambulatory blood pressure (ABP). There is disagreement regarding the optimal cutoff point for ABP. The white-coat effect is operationally defined as the difference between the clinic blood pressure and daytime ABP. PREVALENCE OF WHITE-COAT HYPERTENSION: This varies according to the definition of white-coat hypertension and the population studied, but is approximately 20% among mild hypertensives, and increases with age. METABOLIC AND BIOCHEMICAL ASPECTS Authors of some studies have suggested that white-coat hypertension is associated with metabolic abnormalities such as hyperlipidemia that lead to an increase in cardiovascular risk, but most have not found this. TARGET-ORGAN DAMAGE: Several measures of target-organ damage have been compared among normotensives, white-coat hypertensives, and sustained hypertensives; these include left ventricular mass, microalbuminuria, and carotid atherosclerosis. In general, target-organ damage in white-coat hypertension is less than that in sustained hypertension, but in some studies it has been found to be more prevalent than in normotensives. MORBIDITY AND MORTALITY Authors of a relatively small number of prospective studies have concluded that white-coat hypertensives have a lower risk of morbidity than do sustained hypertensives, but a larger number have drawn the more general conclusion that, when there is a discrepancy between the clinic blood pressure and ABP, the prognosis is more closely related to the ABP. MANAGEMENT When white-coat hypertensives are prescribed antihypertensive medication there is usually a decrease in clinic blood pressure, but little or no change in ABP. Thus drug treatment is not necessarily indicated. Another issue is the follow-up of white-coat hypertensives; there is general agreement that blood pressure outside the office should be monitored indefinitely. Some patient may have been wrongly classified as white-coat hypertensives, and others may progress to develop sustained hypertension.

Sympathetic tone restrains arterial distensibility of healthy and atherosclerotic subjects.

Abstract: Background Sympathetic activation induced by cold pressor test or cigarette smoking is accompanied by a marked reduction of radial artery distensibility. It is not known, however, whether arterial distensibility is under tonic sympathetic restraint, or whether this restraint involves arteries greater than the radial one in both normal and pathological conditions. Methods We studied the distensibility of radial artery by continuous ultrasonographic assessment of the changes in arterial diameter over the diasto-systolic pressure range (finger pressure measurement) in eight patients with a Dupuytren disease before and 20 min after ipsilateral brachial plexus anaesthesia. We also studied ultrasonographic distensibility of femoral artery in seven subjects before and 20 min after ipsilateral subarachnoid anaesthesia, performed before arthroscopic surgery, and in five patients with claudicatio intermittens before and 1 month after ipsilateral removal of the lumbar sympathectomy chain. In all three conditions, the contralateral artery served as control. Results The three interventions did not cause any significant alteration in blood pressure and heart rate. Radial artery distensibility was markedly increased by ipsilateral anaesthesia of the brachial plexus (+36%, P < 0.01). This was the case also for femoral artery distensibility both following ipsilateral subarachnoid anaesthesia in healthy subjects (+47%, P< 0.05) or ipsilateral sympathetic gangliectomy in patients with peripheral artery disease (+26%, P< 0.05). In all three instances, the distensibility of the contralateral artery remained unaffected. Conclusions These data indicate that the sympathetic nervous system exerts a marked tonic restraint of arterial distensibility. This restraint involves medium-size and large muscular arteries and can also be seen in subjects with peripheral artery disease. This stiffening influence may increase the traumatic effect of intravascular pressure on the vessel wall and favour atherosclerosis.

Muscle and Skin Sympathetic Nerve Traffic During the “White-Coat” Effect

Abstract: Background—Sphygmomanometric blood pressure measurements induce an alerting reaction and thus an increase in the patient’s blood pressure and heart rate. Whether and to what extent this “white-coat” effect is accompanied by detectable changes in sympathetic nerve traffic has never been investigated. Methods and Results—In 10 mild untreated essential hypertensives (age 37.9±3.8 years, mean±SEM), we measured arterial blood pressure (by Finapres), heart rate (by ECG), and postganglionic muscle and skin sympathetic nerve activity via microneurography. Measurements were performed with the subject supine during (1) a 15-minute control period, (2) a 10-minute visit by a doctor unfamiliar to the patient who was in charge of measuring his or her blood pressure by sphygmomanometry, and (3) a 15-minute recovery period after the doctor’s departure. The entire procedure was performed twice at a 45-minute interval to obtain, in separate periods, muscle or skin sympathetic nerve traffic recordings, whose sequence was ra...

Reliability and limitations of echocardiographic measurement of left ventricular mass for risk stratification and follow-up in single patients: The RES trial

Abstract: Objective To investigate the clinical reliability of repeated measurements of left ventricular mass in a single patient Design We used test-retest reliability analysis, within-class correlation and interval of agreement measures. Methods Two M-mode tracings (three consecutive cycles) were recorded in the same session and 3-10 days apart (5 ± 2 days; mean ± SD) in 261 participants (age 45 ± 13 years, body mass index 24.7 ± 3.6 kg/m 2 ; 131 hypertensive and 130 normotensive; 50% of each group women) in 16 centres in Italy. The two tracings were read by two observers in each centre, after classification by a three-order quality score (1 = poor, 2 = sufficient, 3 = optimal). Results The average quality score was 2.11 ± 0.71 (21% poor, 50% sufficient, 29% optimal). Left ventricular mass values ranged from 56 to 419 g (170 ± 61 g). On the same day, within-observer 90% interval of agreement between tracing 1 and tracing 2 was -28 to +22 g (-17 to +11% of tracing 1). For day-to-day test-retest within-observer variability (average three cycles), the 90% interval of agreement was -30 to +35 g (-18 to +18%). This variability decreased to -13 to +12% at the 80% interval of agreement and -12 to +11% at the 75% interval of agreement. The 90% interval of agreement of test-retest between-observer variability was -26 to 30 g (-19 to +15%). A negligible regression toward the mean was identified. Categorical consistency of retest in the identification of hypertensive patients with left ventricular hypertrophy, classified in the first study, was 87% (k=0.87). Conclusions Measurement of left ventricular mass in single patients allows reliable risk stratification on the basis of the presence of left ventricular hypertrophy. The probability of a true change in left ventricular mass over time is maximized for a single-reader difference greater than 18% of the initial value, although differences of 10-13% might also have clinical relevance.

Heart Rate-Dependent Stiffening of Large Arteries in Intact and Sympathectomized Rats

Abstract: In the anesthetized rat, acute increases in heart rate are accompanied by a reduction in arterial distensibility, which is a significant phenomenon in elastic-type vessels such as the common carotid but much less evident in muscle-type vessels such as the femoral artery. Because the sympathetic nervous system importantly reduces arterial distensibility, the present study aimed to determine whether sympathetic influences (1) are involved in the heart rate-dependent changes in arterial distensibility and (2) exert differential effects on elastic-type versus muscle-type arteries. To address this issue, 9 sympathectomized (6-hydroxydopamine) and 10 vehicle-treated, 12-week-old, pentobarbitone-anesthetized Wistar-Kyoto rats were subjected to atrial pacing via a transjugular catheter at 5 different randomly sequenced rates (280, 310, 340, 370, and 400 bpm). After each step, spontaneous sinus rhythm was allowed to return to normal. Common carotid and femoral artery diameters were measured by an echo Doppler device (NIUS 01), and blood pressure was measured via catheter inserted into the contralateral vessel. Arterial distensibility was calculated over the systolic-diastolic pressure range according to the Langewouters formula. In the common carotid artery, progressive increases in heart rate determined progressive and marked reductions of distensibility (range, 15% to 43%) in sympathectomized and intact rats. In the femoral artery, the stiffening effect of tachycardia was present in sympathectomized rats (range, 21% to 42%), at variance with the inconsistent changes observed in intact rats. In conclusion, our experiments support the notions (1) that in predominantly elastic-type arteries, the stiffening effect of tachycardia is exerted independently of sympathetic modulation of the vessel wall properties and (2) that in predominantly muscle-type arteries, removal of sympathetic influences unmasks the stiffening effect of tachycardia.

Fluctuations of radial artery distensibility throughout the menstrual cycle.

Abstract: Estrogen administration has a number of favorable cardiovascular effects, and recent evidence suggests that these include an increase in arterial distensibility. Whether this is also the case for the physiological changes in estrogen production during the menstrual cycle has never been determined, however. In 21 premenopausal healthy women, we continuously measured radial artery diameter and blood pressure by an echo-tracking device and a beat-to-beat finger device, respectively. Arterial distensibility was calculated as distensibility/blood pressure curve. The measurements were made during the follicular, ovulatory, and luteal phases of the menstrual cycle. As expected, compared with the follicular phase, plasma estradiol, follicle-stimulating hormone, luteinizing hormone, and prolactin were increased in the ovulatory phase, whereas progesterone was increased in the luteal phase, together with antidiuretic hormone. Radial artery distensibility was increased in the ovulatory and reduced in the luteal phase, the changes being independent of the small, concomitant blood pressure changes. The arterial wall stiffening seen in the luteal phase was associated with a reduction in the flow-dependent endothelial dilatation of the radial artery as assessed by the hyperemia after short-term ischemia of the hand. Thus, the natural menstrual cycle is characterized by alterations in radial artery distensibility. The mechanisms responsible for this phenomenon remain to be clarified. It is possible, however, that the greater arterial distensibility of the ovulatory phase is due to an estrogen-dependent reduction in vascular smooth muscle tone, whereas the arterial stiffening of the luteal phase depends on vascular smooth muscle contraction due to more complex hormonal phenomena, ie, an endothelial impairment due to estrogen reduction but also to an increase in progesterone and antidiuretic hormone levels.

Effect of sinoaortic denervation on frequency-domain estimates of baroreflex sensitivity in conscious cats

Abstract: In animals and humans, baroreceptor modulation of the sinus node in daily life can be studied by identification of the number of sequences in which systolic blood pressure (SBP) and pulse interval ...

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

Abstract: 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 lenghtenings: 203 ± 43 vs 325 ± 52 ms, respectively, p

Broad-band spectral analysis of 24 h continuous finger blood pressure : comparison with intra-arterial recordings

Abstract: The present study compares the spectral characteristics of 24-h blood pressure variability estimated invasively at the brachial artery level with those estimated by measurement of blood pressure at the finger artery using the non-invasive Portapres device. Broad-band spectra (from 3x10(-5) to 0.5 Hz) were derived from both finger and intra-brachial pressures recorded simultaneously for 24 h in eight normotensive and twelve hypertensive ambulant subjects. At frequencies lower than 0.07 Hz, higher spectral estimates were obtained by Portapres than by intra-brachial measurements. The maximum overestimation occurred in systolic pressure at around 10(-2) Hz, where the amplitude of the oscillations was two times greater when measured by Portapres. A less pronounced overestimation was found for diastolic pressures. The maximum overestimation was greater during daytime than during night-time. At around 0.1 Hz, invasive and non-invasive spectra were similar. At the respiratory frequencies (0.15-0.50 Hz), the power spectra were overestimated by Portapres during daytime, and underestimated at night. These results provide reference information for the correct interpretation of Portapres data in the estimation of 24-h blood pressure spectral power.

Systolic blood pressure and pulse pressure: role of 24-h mean values and variability in the determination of organ damage.

Abstract: An increasing amount of data suggests that systolic blood pressure (SBP) and pulse pressure (PP) may more closely relate to and thus favour the atherogenic process than does diastolic blood pressure (DBP). The baseline data from the ongoing European Lacidipine Study on Atherosclerosis (ELSA) recently indicated that carotid artery atherosclerosis in normocholesterolaemic patients with mild or moderate essential hypertension is more closely related to SBP and more so PP than to DBP and lipid variables. Other new data point to the effects of hypertension on arterial compliance, as well as the effects of 24-h blood pressure variability on arterial compliance and distensibility. When viewed in their entirety, these data present a compelling case for the closer monitoring of SBP and PP with respect to arterial compliance, and the need for aggressive blood pressure treatment to control and perhaps reverse the underlying pathological changes in arterial structure and function in hypertensive patients.

Sympathetic Nerve Traffic Responses to Surgical Removal of Pheochromocytoma

Abstract: Pheochromocytoma is usually characterized by a marked increase in peripheral catecholamine secretion. Whether this is accompanied by an alteration in central sympathetic drive has not been clarified. In 6 patients with adrenal pheochromocytoma (mean+/-SEM age, 49. 3+/-7.2 years), we measured systolic and diastolic blood pressure (photoplethysmographic device), heart rate (ECG), venous plasma catecholamines (high-performance liquid chromatography), and postganglionic muscle sympathetic nerve activity (microneurography) before and 78.3+/-13 days after surgical removal of the tumor. In each experimental session, measurements were performed during (1) a 60-minute resting period to compare several values of sympathetic nerve traffic at similar blood pressures before and after surgery and (2) voluntary end-expiratory apnea, ie, a maneuver inducing sympathetic activation. Tumor removal significantly (P<0.05 at least) reduced plasma catecholamines, blood pressure, and heart rate. In contrast, muscle sympathetic nerve activity was significantly (P<0.01) increased, both when quantified as bursts per minute (from 28.1+/-5.7 to 54.3+/-7.5) and as bursts per 100 heartbeats (from 33. 4+/-5.6 to 65.1+/-6.5). This was also the case when data were evaluated in periods of 2 experimental sessions characterized by similar diastolic blood pressure values. The apnea maneuver induced sympathetic nerve traffic responses that were significantly (P<0.05) greater after surgery than before surgery. These data provide the first direct evidence that in pheochromocytoma central sympathetic outflow is markedly reduced and that this reduction cannot be ascribed to a reflex inhibitory response to elevated blood pressures. It is likely that this sympathoinhibition is rather due to a central depression of sympathetic outflow induced by high circulating catecholamines.

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

Abstract: 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.

Effects of amlodipine on sympathetic nerve traffic and baroreflex control of circulation in heart failure.

Abstract: —Short-acting calcium antagonists exert a sympathoexcitation that in heart failure further enhances an already elevated sympathetic activity. Whether this is also the case for long-acting formulations is not yet established, despite the prognostic importance of sympathetic activation in heart failure. It is also undetermined whether in this condition long-acting calcium antagonists favorably affect a mechanism potentially responsible for the sympathetic activation, ie, the baroreflex impairment. In 28 heart failure patients (NYHA functional class II) under conventional treatment we measured plasma norepinephrine and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during arterial baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were performed at baseline and after 8 weeks of daily oral amlodipine administration (10 mg/d, 14 patients) or before and after an 8-week period without calcium antagonist administration (14 patients). Amlodipine caused a small and insignificant blood pressure reduction. Heart rate, left ventricular ejection fraction, and plasma renin and aldosterone concentrations were not affected. This was the case also for plasma norepinephrine (from 2.43±0.41 to 2.50±0.34 nmol/L, mean±SEM), muscle sympathetic nerve activity (from 54.4±5.9 to 51.0±4.3 bursts/min), and arterial baroreflex responses. No change in the above-mentioned variables was seen in the control group. Thus, in mild heart failure amlodipine treatment does not adversely affect sympathetic activity and baroreflex control of the heart and sympathetic tone. This implies that in this condition long-acting calcium antagonists can be administered without untoward neurohumoral effects anytime conventional treatment needs to be complemented by drugs causing additional vasodilatation.

Task force II: Ambulatory blood pressure monitoring in population studies.

Abstract: Ambulatory blood pressure (ABP) has only rarely been employed in population studies because of the difficulty posed by the greater complexity of this technique. The cross-sectional studies that have been published, however, have allowed a number of conclusions to be drawn. One, 24h average blood pressure of populations is significantly but not closely related to office blood pressure, which thus can not predict accurately daily-life values of blood pressure. Two, 24h average blood pressure is usually less than office blood pressure, the discrepancy increasing with the increase in office values and being of magnitude several mmHg at the office blood pressure of 140/90 mmHg (systolic/diastolic) Three, ABP in women is somewhat less than that in men and ABP for both sexes increases less with aging than does office blood pressure. Four, a circadian profile of blood pressure consisting in values that are much lower at night than are those during daytime characterizes both sexes and all ages with the possible exception of individuals aged 75 years and more, in whom the nocturnal hypotension appears to be attenuated. A similar attenuation has been found for blacks in comparison with whites. The upper limit of normality of ABP has not yet been defined conclusively, although 24h average values

New drugs for the treatment of hypertension.

Abstract: Despite the many outstanding favorable results achieved in the treatment of hypertension, several unmet goals of antihypertensive therapy remain, such as better blood pressure control, greater protection against the organ damage associated with hypertension, better tolerability, and ultimately a more effective prevention of cardiovascular disease. These unmet goals are the reasons why new antihypertensive drugs are synthesized and tested in the clinical practice. This paper briefly mentions the goals of new antihypertensive agents and examines the main pharmacological and clinical features of new classes of antihypertensive drugs, such as angiotensin II receptor blockers, central agents, vasopeptidase inhibitors, and endothelin antagonists. The results of experimental and clinical studies with these new drugs are reviewed, emphasizing some advantages and potential disadvantages of these drugs compared with traditional antihypertensive drugs.

Arterial distensibility and pulse pressure. Measurements and clinical significance in hypertension.

Abstract: Distensibility of large and middle size arteries is a function of major significance for the cardiovascular system. This paper will describe data obtained by measurements of local distensibility in hypertension and other cardiovascular diseases. Isolated systolic hypertension is characterized by a diffuse reduction of arterial distensibility, while essential hypertension by a reduced distensibility in large elastic arteries, but an unchanged distensibility of middle size arteries. Other conditions associated with a marked reduction of arterial mechanical functions are familial hypercholesterolemia, the association of mild hypertension and mild hypercholesterolemia, congestive heart failure and type 1 diabetes mellitus. In most of these conditions, however, appropriate therapy is able to reverse the deranged arterial distensibility. Finally, epidemiological data suggest that it is justified to focus on pulse pressure, i.e. on an indirect indicator of a reduced arterial distensibility, when assessing the overall cardiovascular risk.