Search PubMed⌕ Search

Biomedical subjects

G Mancia

Publications and source records attributed to G Mancia.

At least 55 records · Page 3Linked to original sources
PubMed2001

Baroreflex effectiveness index: an additional measure of baroreflex control of heart rate in daily life.

In healthy subjects, progressive beat-to-beat increases or decreases in systolic blood pressure (SBP) ramps are not always accompanied by baroreflex-driven lengthening or shortening in pulse interval (PI) ramps, respectively. This phenomenon has been quantified by a new index, the baroreflex effectiveness index (BEI), defined as the ratio between the number of SBP ramps followed by the respective reflex PI ramps and the total number of SBP ramps observed in a given time window. Specificity of BEI was shown in eight cats by a -89% reduction of BEI after sinoaortic denervation. In 14 healthy humans, the 24-h average BEI value was 0.21, with a marked day-night modulation ( approximately 0.25 day, approximately 0.15 night) in counterphase with modulation of baroreflex sensitivity (BRS). Our analysis indicates that 1) in normal subjects, arterial baroreflex can induce beat-by-beat PI changes in response to only 21% of all SBP ramps, possibly because of central inhibitory influences or of interferences at sinus node level by nonbaroreflex mechanisms and 2) BEI provides information on the baroreflex function that is complementary to BRS.

Adult↗
PubMed2001

Effects of chronic clonidine administration on sympathetic nerve traffic and baroreflex function in heart failure.

Congestive heart failure is characterized by a sympathetic activation that is coupled with a baroreflex impairment. Whether these alterations are affected by clonidine is unknown. In 26 normotensive patients age 58.0+/-1.1 years (mean+/-SEM) affected by congestive heart failure (New York Heart Association functional class II or III) and treated with furosemide and enalapril, we measured mean arterial pressure, heart rate, venous plasma norepinephrine, and muscle sympathetic nerve traffic (microneurography) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, randomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity and echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were significantly reduced (-46.8% and -26.7%, respectively; P<0.01 for both). This reduction was coupled with no change in cardiac and sympathetic baroreflex responses. Transdermal placebo administration for a 2-month period did not affect any of the above-mentioned variables. Thus, in congestive heart failure patients who are undergoing conventional drug treatment, chronic clonidine administration exerts marked sympathoinhibitory effects without adversely affecting cardiac functions and clinical state. Whether this leads to further therapeutic benefits remains to be tested.

Baroreflex↗
PubMed2001

Cardiovascular effects of an earthquake: direct evidence by ambulatory blood pressure monitoring.

The increased cardiovascular mortality during an earthquake has been related, among other factors, to a sympathetically mediated increase in heart rate and blood pressure. However, this is supported only by indirect evidence collected after an earthquake, whereas for obvious technical difficulties, no data are available on the acute blood pressure and heart rate effects during an earthquake. In a patient undergoing 24-hour ambulatory blood pressure monitoring (Spacelabs 90207), we had the opportunity to directly record the acute blood pressure and heart rate changes induced by an earthquake (magnitude 4.7 according to the Richter scale) that struck central Italy in March 1998. Systolic blood pressure rose to 150 mm Hg, diastolic blood pressure rose to 122 mm Hg, and heart rate rose to 150 bpm at the time of the strongest tremor. Prequake blood pressure levels were restored only 1 hour later, but blood pressure remained characterized by a pronounced variability throughout the following 6 hours. Thus, a sympathetically mediated combined increase in blood pressure and heart rate may represent an important pathophysiological mechanism responsible for the increased frequency of cardiovascular events during an earthquake. The associated increase in blood pressure variability might further contribute to the increase in cardiovascular risk typical of this condition. Our case report further supports the usefulness of ambulatory blood pressure monitoring to assess the blood pressure and heart rate effects of sudden daily life events, the actual cardiovascular impact of which can hardly be quantified through traditional measurements.

Adult↗
PubMed2001

Local effects of atherosclerotic plaque on arterial distensibility.

Hypertension, diabetes, and hypercholesterolemia are characterized by a reduction in arterial distensibility and by accelerated atherosclerosis. Whether arterial stiffening is an inherent feature of these conditions or just the consequence of the atherosclerotic clinical or subclinical lesions is not known, however. Our aim was to obtain information on this issue by directly measuring, in humans, arterial distensibility both at the site of an atherosclerotic lesion and at the proximal normal site. In 10 patients (8 men; mean+/-SEM age, 65.2+/-3.4 years) affected by monolateral hemodynamic significant internal carotid artery stenosis, we measured arterial distensibility (Wall Track System; PIE Medical) bilaterally, both at the internal carotid artery and at the common carotid artery level. In the common carotid artery, measurements were made 3 cm below the bifurcation. In the affected internal carotid artery, measurements were made at the plaque shoulder (wall thickness of 2 mm). Measurements were made in the contralateral internal carotid artery at a symmetrical level. Arterial wall thickness was measured in the same site of arterial distensibility. Arterial distensibility was less in the internal than in the common carotid artery, with a marked reduction at the plaque internal carotid artery level compared with the corresponding contralateral site (-45%, P<0.01). It was also less, however, in the common carotid artery branching into the atherosclerotic internal carotid artery than in the contralateral common carotid artery (-25%, P<0.05). Wall thickness was similar in the 2 common carotid arteries and obviously greater in the affected internal carotid artery than in the contralateral artery. Arterial distensibility was markedly less in the internal carotid artery where there was a plaque compared with the intact contralateral internal carotid artery; it was also less, however, in the common carotid artery of the affected side in comparison with the contralateral common carotid artery. This provides evidence that the effect of a plaque on arterial mechanical properties is not limited to the actual plaque site but rather extends to a considerable degree in a proximal direction.

Aged↗
PubMed2001

[Blood pressure variability].

This review deals with a number of issues related to blood pressure variability. These include: historical aspects, with reference to the first pioneering observations; methodological aspects, focusing on the different methods for quantifying blood pressure variability; description of the characteristics of blood pressure variability over the 24 hours; mechanisms involved in determining the different magnitude of this phenomenon in different subjects, such as behavioral factors, central and reflex neural influences, humoral and mechanical factors; blood pressure variability as a probe to assess spontaneous baroreflex sensitivity; effects of aging and hypertension on blood pressure variability, with a discussion of the clinical relevance of this phenomenon in the prognostic evaluation of patients; effects of drugs on blood pressure variability. Finally methodological aspects related to the use of noninvasive ambulatory blood pressure monitoring in the assessment of blood pressure variability are discussed.

Aging↗
PubMed2001

Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy.

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n=22, age 60.3+/-2.4 years, means+/-S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n=20, age 58.9+/-2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3+/-4.2 and 67.8+/-3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

Adult↗
PubMed2001

[Clinical applications of methods for assessing the autonomic nervous system].

This paper will review the usefulness of the evaluation of the autonomic control in cardiovascular and non-cardiovascular diseases, such as heart failure, hypertension, myocardial infarction and diabetes. Emphasis will be given to the relevance of the parasympathetic/sympathetic alterations found in the above-mentioned conditions in determining the cardiovascular risk profile of the individual patient.

Autonomic Nervous System↗
PubMed2001

Meta-analysis of studies using selective alpha1-blockers in patients with hypertension and type 2 diabetes.

This meta-analysis of published studies evaluated the effect of selective alpha1-blockers on lipid and carbohydrate profiles and blood pressure (BP) as well as tolerability in patients with hypertension and type 2 diabetes. Publications identified via MEDLINE were used. Text and bibliographies of retrieved articles were examined for additional references. Clinical trials with a randomised comparative structure (placebo and active treatment arms) and controlled studies with other structures were included. Of the 27 citations identified, 22 studies were selected for inclusion, and five were rejected. Efficacy and safety data, lipid and carbohydrate profiles, and study and patient characteristics were extracted by two investigators independently. The mean pooled results showed beneficial effects of selective alpha1-blockers on total serum cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and systolic and diastolic BP. The results also showed doxazosin had beneficial effects on fasting glucose levels, insulin sensitivity, TC, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, HDL/TC ratio, and systolic and diastolic BP. The risk difference was equivalent between the alpha1-blocker group and the control group for postural hypotension or syncope. This meta-analysis demonstrates a number of favourable effects of therapy with selective alpha1-blockers in hypertensive patients with type 2 diabetes. These agents provide an effective modality for reducing BP, with favourable effects on lipid, no deterioration in glycaemic control, and little risk of orthostatic hypotension.

Adrenergic alpha-Antagonists↗
PubMed2000

Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT).

BACKGROUND: The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension. METHODS: We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 mg [corrected] plus amiloride 2.5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat. FINDINGS: Primary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0.81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0.33% [-0.7 to 1.4]). INTERPRETATION: Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy.

Aged↗
PubMed2000

Modulation of sympathetic coronary vasoconstriction by cardiac renin-angiotensin system in human coronary heart disease.

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 microgram/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 superimposable during saline and benazeprilat infusions. The decrease in CBF induced by CPT and diving during saline infusion was changed into an increase during benazeprilat infusion with a significant attenuation of the coronary vasoconstrictor response. CONCLUSIONS: In patients with coronary artery disease, an attenuation of sympathetic coronary vasoconstriction can be obtained by reducing cardiac angiotensin II formation without involving circulating angiotensin II. This suggests a role of the tissue renin-angiotensin system in modulating autonomic cardiac drive in humans.

Aged↗
PubMed2000

Sympathoexcitatory responses to the acute blood pressure fall induced by central or peripheral antihypertensive drugs.

This study was designed to evaluate the effects of an acute blood pressure reduction brought about by a peripheral vasodilator agent (prazosin) or by a drug combining central and peripheral modes of action (urapidil), on three markers of adrenergic tone such as muscle sympathetic nerve traffic (MSNA), venous plasma norepinephrine (NE), and heart rate (HR). In 12 untreated essential hypertensives (age, 50.7 +/- 1.9 years; mean +/- SEM), we evaluated in two experimental sessions, according to a double-blind crossover design, the effects of acute oral administration of 2 mg prazosin or 30 mg urapidil on beat-to-beat finger blood pressure (Finapres), HR (electrocardiogram), NE (high-performance liquid chromatography), and MSNA (microneurography at a peroneal nerve). In each session measurements were performed in the no-drug control state and repeated throughout a 3-h period after drug administration. For similar blood pressure reductions, the two drugs caused similar increases in NE and MSNA (peak effects: NE = +1.1 +/- 0.2 vs 0.9 +/- 0.2 nmol/L and MSNA = +10.9 +/- 1.8 vs +10.1 +/- 1.6 bursts/min for prazosin and urapidil respectively, P = ns between drugs), whereas HR increased more markedly after prazosin administration (+6.1 +/- 1.1 vs +2.4 +/- 0.8 beats/min, P < 0.05). These data provide evidence that acute blood pressure reductions induced by antihypertensive drugs with central or peripheral modes of action activate the sympathetic nervous system to a similar extent. Thus adrenergic activation is not peculiar to vasodilators but rather generalized to any drug-induced acute blood pressure fall, presumably because of the lack of a baroreflex resetting, which occurs during chronic but not during acute antihypertensive treatment.

Adult↗
PubMed2000

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

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

Adult↗
PubMed2000

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

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.

Adult↗
PubMed2000

Two novel nonsense mutations of HFE gene in five unrelated italian patients with hemochromatosis.

BACKGROUND & AIMS: Most hemochromatosis patients of Northern European descent are homozygous for the C282Y mutation of HFE gene. In Italy, many patients with iron overload are not homozygous for C282Y, and the presence of other mutations or other genetic determinant has been suggested. METHODS: Five unrelated Italian patients heterozygous for C282Y with the classic hemochromatosis phenotype were studied. The entire coding sequence and the exon-intron boundaries of the HFE gene were analyzed. Chromosome 6p haplotypes were defined in each patient by analysis of D6S265, D6S105, and D6S1281 microsatellites. RESULTS: Two novel nonsense HFE mutations were identified in exon 3 in the C282Y negative chromosome. The first one, a G-to-T transition at codon 168, was detected in 3 probands; the second, a G-to-A transition at codon 169, was detected in the others. CONCLUSIONS: The 2 nonsense mutations in the compound heterozygous state with C282Y result in the classic hemochromatosis phenotype in several unrelated Italian patients. This confirms that hemochromatosis in Italy is not as homogeneous as in northern Europe and suggests that other mutations can exist in C282Y or H63D heterozygotes with iron overload. These findings have practical implications for diagnostic and screening strategies for hemochromatosis.

Adult↗
PubMed2000

Radial artery wall alterations in genetic hemochromatosis before and after iron depletion therapy.

Iron overload is believed to have an adverse influence on the cardiovascular system and animal studies have shown that iron may be involved in the events that lead to atherosclerosis via an enhancement of smooth muscle cell proliferation, lipid oxidation, and free radical production. There are no data on the effect of iron overload on arterial structural and mechanical properties in humans. We measured wall thickness and distensibility (D) by ultrasonography of the radial artery in 12 patients with uncomplicated genetic hemochromatosis (GH) who were normotensive and without atherosclerotic plaques. Twelve age- and sex-matched patients were taken as controls. Nine patients were evaluated also after iron depletion. Wall thickness was greater in patients with GH than in controls (+50%, P <.01) whereas D was slightly reduced in the former group compared with the latter group, though the difference was not statistically significant. After iron depletion, a significant reduction of wall thickness and a significant increase in D were observed (-24% and +33%, P <.05 for both). Thus, in patients with hemochromatosis, arterial wall thickness is increased before the onset of cardiovascular complications. This alteration is reverted by iron depletion, which also can improve the initial and modest radial artery wall stiffening associated with this condition. Thus, functional and structural alterations in midsize muscle arteries may be an early abnormality of hemochromatosis.

Adult↗
PubMed2000

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

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.

Adult↗