Search PubMed⌕ Search

Biomedical subjects

Giuseppe Mancia

Publications and source records attributed to Giuseppe Mancia.

At least 19 recordsLinked to original sources
PubMed2007

Excessive sympathetic activation in heart failure with obesity and metabolic syndrome: characteristics and mechanisms.

Congestive heart failure is characterized by sympathetic activation, which has also been described in the metabolic syndrome. No information exists, however, as to whether the sympathostimulating effects of these 2 conditions summate when heart failure is complicated by the metabolic syndrome, leading to an exceedingly high adrenergic drive. This is clinically relevant, because in heart failure sympathetic activation is closely related to mortality. We studied 48 control subjects (age: 58.4+/-1.6 years, mean+/-SEM) and 89 age-matched heart failure patients (New York Heart Association class II), of whom 47 were without and 42 were with metabolic syndrome. Measurements included blood pressure (Finapres), heart rate (ECG), and sympathetic nerve traffic (microneurography) at rest and during baroreceptor manipulation. Waist circumference, blood pressure, and metabolic variables were greater in heart failure with metabolic syndrome than in heart failure without metabolic syndrome and in control subjects. Left ventricular ejection fraction and end-diastolic diameter were similarly altered in the 2 heart failure groups. Compared with control subjects, sympathetic nerve activity was greater in heart failure patients without metabolic syndrome (64.7+/-3.2 versus 45.8+/-2.9 bursts/100 heartbeats; P<0.01), a further pronounced increase being detected in those with metabolic syndrome (80.9+/-3.2 bursts/100 heartbeats; P<0.01). In the multivariate analysis, waist circumference and body mass index were the variables most closely related to sympathetic activation. Compared with control subjects, baroreflex responses were significantly attenuated in the 2 heart failure groups, the impairment being more marked in the group with than without metabolic syndrome. Thus, obesity and metabolic syndrome potentiate the sympathetic activation characterizing heart failure. This potentiation is likely to mainly depend on metabolic and baroreflex mechanisms.

Aged↗
PubMed2007

How reliable is isolated clinical hypertension defined by a single 24-h ambulatory blood pressure monitoring?

BACKGROUND: Isolated clinical hypertension (ICH) is characterized by a persistently elevated clinic blood pressure in the presence of a normal day-time or 24-h ambulatory blood pressure (ABP). This definition is based on a single ABP monitoring (ABPM) and little attention has been focused on the reproducibility of this condition. OBJECTIVE: To investigate the reliability of the criteria currently recommended by major hypertension guidelines to detect ICH based on a single 24-h ABPM session. METHODS: A total of 611 never-treated grade 1 and 2 hypertensive patients (mean age 46 +/- 12 years) referred for the first time to our out-patient clinic, underwent repeated clinic blood pressure measurements, routine investigations, two 24-h periods of ABPM 1-4 weeks apart, cardiac and carotid ultrasound examinations. ABPM was always performed over a working day and the same daily activities were recommended during the two periods. ICH was diagnosed by the following criteria: (i) mean daytime values < 135/85 mmHg or (ii) mean 24-h blood pressure values < 125/80 mmHg during the first ABPM. RESULTS: The overall prevalence of ICH was 7.1% according to criterion (i) and 5.4% according to criterion (ii). Twenty (46.6%) of the 43 patients with mean daytime blood pressure values < 135/85 mmHg during the first ABPM, exceeded this cut-off value during the second ABPM period. Twenty-two (66.6%) of the 33 patients with mean 24-h blood pressure values < 120/80 mmHg during the first ABPM did not confirm a normal blood pressure profile during the second ABPM recording. Cardiovascular involvement was significantly lower in subjects with persistent normal ABP compared to those with non-reproducible ICH pattern or sustained hypertensives. CONCLUSIONS: These findings clearly indicate that: (i) the classification of ICH on the basis of a single ABPM, using the cut-offs suggested by major hypertension guidelines, has a limited short-term reproducibility and (ii) repeated ABPM recordings should be recommended to correctly diagnose patients with ICH and improve cardiovascular risk stratification.

Adult↗
PubMed2006

Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: daily life blood pressure, cardiac damage, and prognosis.

The prevalence of the metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III criteria) and its relationships with daily life blood pressures, cardiac damage, and prognosis were determined in 2013 subjects from a Northern Italian population aged 25 to 74 years. Home blood pressure, 24-hour blood pressure, and left ventricular mass index (echocardiography) were also measured. Cardiovascular and noncardiovascular deaths were registered over 148 months. Metabolic syndrome was found in 16.2% of the sample, an office blood pressure elevation being the most frequent (95.4%) and the blood glucose abnormality the least frequent (31.5%) component. There was in metabolic syndrome a frequent elevation in home and/or 24-hour average blood pressure, as well as a greater left ventricular mass index and prevalence of left ventricular hypertrophy, which was manifest even when data were adjusted for between-group differences, including blood pressure. The adjusted risk of cardiovascular and all-cause mortality was greater in metabolic syndrome subjects (+71.0% and +37.0%; P<0.05), a further marked increase being observed with left ventricular hypertrophy or "in-office" and "out-of-office" blood pressure elevations. The increased risk was related to the blood pressure and the blood glucose component of metabolic syndrome, with no contribution of the remaining components. Thus, metabolic syndrome is common in a Mediterranean population in which it significantly increases the long-term risk of death. Cardiac abnormalities and increases in home and 24-hour blood pressure are common in metabolic syndrome, and their occurrence further enhances the risk. The contribution of metabolic syndrome components to the risk, however, is unbalanced and mainly related to blood pressure and glucose abnormalities.

Adult↗
PubMed2006

Enhanced baroreceptor control of the cardiovascular system by polyunsaturated Fatty acids in heart failure patients.

OBJECTIVES: The intention of this study was to test the hypothesis that, in heart failure patients, dietary supplementation of polyunsaturated fatty acids (PUFA) enhances arterial baroreceptor control of the cardiovascular system. BACKGROUND: Administration of PUFA reduces the risk of life-threatening arrhythmias in patients surviving myocardial infarction. This might result from potentiation of arterial baroreflexes, but whether or not PUFA enhance baroreflex function has never been studied in humans. METHODS: Patients with post-myocardial infarction left ventricular dysfunction underwent beat-to-beat blood pressure (BP) (Finapres, Ohmeda Inc., Englewood, Colorado) and R-R interval (electrocardiogram) recording; baroreceptor reflexes were assessed from the bradycardic and depressor responses to graded neck suction (NS) as well as by computation of the alpha "spontaneous" baroreflex sensitivity index. Assessments were repeated after prolonged treatment with PUFA (2 g/die, n = 15) or placebo (n = 10). RESULTS: Baseline BP and R-R interval were unaffected by PUFA. Both reflex depressor and bradycardic responses to NS increased after PUFA (respectively from -0.09 +/- 0.01 to -0.16 +/- 0.01 mm Hg x mm Hg(-1), p < 0.01, and from 1.25 +/- 0.9 to 1.76 +/- 1.1 ms x mm Hg(-1), p < 0.04) but not after placebo. The spontaneous baroreflex sensitivity increased in the PUFA (from 8.99 +/- 1.4 to 12.2 +/- 1.2 ms x mm Hg(-1), p < 0.02) but not in the placebo group. Polyunsaturated fatty acids (but not placebo) treatment also significantly increased R-R interval total variance and low-frequency and high-frequency spectral powers. CONCLUSIONS: Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure.

Baroreflex↗
PubMed2006

Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) study.

BACKGROUND: The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1. The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension, renal water, and sodium balance under acute and prolonged exposure to high-altitude-associated hypoxia. METHODS AND RESULTS: In a double-blind fashion, healthy volunteers were randomly assigned to receive bosentan (62.5 mg for 1 day and 125 mg for the following 2 days; n=10) or placebo (n=10) at sea level and after rapid ascent to high altitude (4559 m). At sea level, bosentan did not induce any significant changes in hemodynamic or renal parameters. At altitude, bosentan induced a significant reduction of systolic pulmonary artery pressure (21+/-7 versus 31+/-7 mm Hg, P<0.03) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment. However, both urinary volume and free water clearance (H2OCl/glomerular filtration rate) were significantly reduced versus placebo after 2 days of ET-1 antagonism (1100+/-200 versus 1610+/-590 mL; -6.7+/-3.5 versus -1.8+/-4.8 mL/min, P<0.05 versus placebo for both). Sodium clearance and segmental tubular function were not significantly affected by bosentan administration. CONCLUSIONS: The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation. These findings must be considered for the prevention and treatment of acute mountain sickness.

Acute Disease↗
PubMed2006

Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous?

BACKGROUND: Because coronary perfusion occurs mainly during diastole, patients with coronary artery disease (CAD) could be at increased risk for coronary events if diastolic pressure falls below critical levels. OBJECTIVE: To determine whether low blood pressure could be associated with excess mortality and morbidity in this population. DESIGN: A secondary analysis of data from the International Verapamil-Trandolapril Study (INVEST), which was conducted from September 1997 to February 2003. SETTING: 862 sites in 14 countries. PATIENTS: 22 576 patients with hypertension and CAD. INTERVENTIONS: Patients from INVEST were randomly assigned to a verapamil sustained-release- or atenolol-based strategy; blood pressure control and outcomes were equivalent. MEASUREMENTS: An unadjusted quadratic proportional hazards model was used to evaluate the relationship between average on-treatment blood pressure and risk for the primary outcome (all-cause death, nonfatal stroke, and nonfatal myocardial infarction [MI]), all-cause death, total MI, and total stroke. A second model adjusted for differences in baseline covariates. RESULTS: The relationship between blood pressure and the primary outcome, all-cause death, and total MI was J-shaped, particularly for diastolic pressure, with a nadir at 119/84 mm Hg. After adjustment, the J-shaped relationship persisted between diastolic pressure and primary outcome. The MI-stroke ratio remained constant over a wide blood pressure range, but at a lower diastolic blood pressure, there were substantially more MIs than strokes. An interaction between decreased diastolic pressure and history of revascularization was observed; low diastolic pressure was associated with a relatively lower risk for the primary outcome in patients with revascularization than in those without revascularization. LIMITATIONS: This is a post hoc analysis of hypertensive patients with CAD. CONCLUSIONS: The risk for the primary outcome, all-cause death, and MI, but not stroke, progressively increased with low diastolic blood pressure. Excessive reduction in diastolic pressure should be avoided in patients with CAD who are being treated for hypertension.

Aged↗
PubMed2006

Survival benefits of different antiadrenergic interventions in pressure overload left ventricular hypertrophy/failure.

We observed previously that in rats with aortic banding (Bd), development of left ventricular (LV) hypertrophy is opposed by beta-blockade, whereas interventions interfering with alpha-adrenoceptor function also inhibit interstitial fibrosis. To assess whether these differential structural effects do translate into different effects on LV function and on heart failure mortality, Bd or sham Bd 8-week-old rats were randomized to vehicle treatment (Vh), chemical sympathectomy ([Sx] 6-hydroxydopamine, 150 mg/kg IP twice a week), beta-adrenoceptor blockade (propranolol [Pro], 40 mg/kg per day PO), or alpha-adrenoceptor blockade (doxazosin [Dox], 5 mg/kg per day PO). After monitoring survival for 10 weeks, the survivors were anesthetized to undergo echocardiography and intraarterial blood pressure measurement. Bd-Vh rats showed increased LV and lung weights, as well as LV dilation, depressed endocardial and midwall fractional shortening and a restrictive transmitral diastolic flow velocity pattern. Compared with Bd-Vh rats, all of the actively treated Bd rats showed less LV hypertrophy, LV dilation, and lung congestion but no less depression of midwall fractional shortening. In contrast, Sx and Dox but not Pro treatment were also associated with lesser degrees of diastolic dysfunction and, even more importantly, with a striking increase in survival (sham banded rats, 100%; Bd-Vh, 40%; Bd-Pro, 51%; Bd-Sx, 83%; and Bd-Dox, 82%). Although Pro, Sx, and Dox provide similar midterm protection from development of LV hypertrophy and dysfunction and from circulatory congestion, only Sx and Dox favorably affected mortality. These findings indicate that in the aortic banding rat model, alpha-adrenoceptors are importantly involved in the pathogenesis of cardiovascular deterioration and disease progression.

Adrenergic alpha-Antagonists↗
PubMed2006

Long-term risk of mortality associated with selective and combined elevation in office, home, and ambulatory blood pressure.

In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, office, home, and ambulatory blood pressure (BP) values were measured contemporaneously between 1990 and 1993 in a large population sample (n=2051). Cardiovascular (CV) and non-CV death certificates were collected over the next 148 months, which allowed us to assess the prognostic value of selective and combined elevation in these 3 BPs over a long follow-up. There were 69 CV and 233 all-cause deaths. Compared with subjects with normal office and 24-hour BP, the hazard ratio for CV death showed a progressive increase in those with a selective office BP elevation (white-coat hypertension), a selective 24-hour BP elevation (masked hypertension), and elevation in both office and 24-hour BP. This was the case also when the above conditions were identified by office versus home BP values. Selective elevation in home versus ambulatory BP or vice versa also carried an increased risk. There was indeed a progressive increase in both CV and all-cause mortality risk from subjects in whom office, home, and ambulatory BP were all normal to those in whom 1, 2, or all 3 BPs were elevated, regardless of which BP was considered. The trends remained significant after adjustment for age and gender, as well as, in most instances, after further adjustment for other cardiovascular risk factors. Thus, white-coat hypertension and masked hypertension, both when identified by office and ambulatory or by office and home BPs, are not prognostically innocent. Indeed, each BP elevation (office, home, or ambulatory) carries an increase in risk mortality that adds to that of the other BP elevations.

Adult↗
PubMed2006

Predictors of adverse outcome among patients with hypertension and coronary artery disease.

OBJECTIVES: We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD). BACKGROUND: Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies. METHODS: We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling. RESULTS: Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk. CONCLUSIONS: In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Guiding antihypertensive treatment decisions using ambulatory blood pressure monitoring.

Compared with isolated clinic measurements, ambulatory blood pressure monitoring (ABPM) provides an insight into blood pressure (BP) changes in everyday life and an estimate of the overall BP load exerted on the cardiovascular system over 24 hours. Cross-sectional evidence suggests a direct and significant relationship between ambulatory BP and organ damage. There is also longitudinal evidence for a superior predictive value of 24-hour BP in relation to the risk for cardiovascular morbidity and mortality as opposed to clinic BP. The usefulness of ABPM in pharmacologic studies aimed at evaluating the 24-hour antihypertensive efficacy of different drugs and drug combinations is now acknowledged. Among the mathematical indices available to explore 24-hour BP coverage by treatment, the ABPM-derived smoothness index provides a superior measure of the homogeneity of BP control compared with trough:peak ratios. The main applications of clinical practice should be in identifying patients with isolated office hypertension and those who are nonresponders to treatment, in assessing coverage of the 24-hour BP profile in high-risk patients and in diagnosing suspected treatment-related hypotension.

Antihypertensive Agents↗
PubMed2006

New-onset diabetes and antihypertensive drugs.

Observational studies have provided evidence that a consistent fraction (approximately 15-20%) of hypertensive patients displays a glucose intolerance state that may be aggravated by antihypertensive drug regimens based on thiazide diuretics or beta-blockers. This review examines the relative and absolute diabetogenic effects of antihypertensive drugs, by comparing the impact of 'new' (calcium antagonists, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists) versus 'old' (diuretics and beta-blockers) drugs on new-onset diabetes in recent clinical trials. Evidence is provided that compared with diuretics and beta-blockers, new-onset diabetes is less common with 'new' drugs, and that conventional antihypertensive compounds, particularly when combined together, may amplify the natural time-dependent tendency towards the development of this metabolic disease. This paper provides new insights into the potential mechanisms responsible for the phenomenon and the clinical significance of antihypertensive drug-induced diabetes.

Adrenergic beta-Antagonists↗