[The APULIA HF multicenter study: efficacy of a management protocol shared between hospital and territorial health services for acute decompensated heart failure patients]. / Studio multicentrico APULIA HF: efficacia di un protocollo di gestione condiviso fra ospedale e territorio dei pazienti ospedalizzati per scompenso cardiaco acuto.

BACKGROUND: The aim of this study was to demonstrate the efficacy of a management model to reduce hospitalizations in patients recently admitted for acute decompensated heart failure. METHODS: The management model was based on a close integration between hospital and territory health services. Clinical evaluation, ECG, echocardiographic findings, total body bioimpedance and brain natriuretic peptide serum levels were used to assess clinical stability of patients at discharge and during follow-up. A dedicated nurse (care manager) was involved in patient empowerment, telephone follow-up, check of adherence to therapy and clinical conditions, and management of scheduled evaluations. All hospitalizations occurring prior to or after enrolment in the municipalities involved in the study were considered, as well as the hospitalizations occurring among enrolled patients. RESULTS: A total of 301 patients were enrolled, 226 of them from the Centers of the Puglia Region, Italy. An overall reduction of 6% in total hospitalizations with DRG 127 was observed; the reduction was most evident in the two centers with the smaller reference population (-16% and -26%, respectively). In the group of patients enrolled, an overall reduction in hospital admissions was observed after comparing the period before and after enrolment. A significant increase in the prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, beta-blockers and aldosterone antagonists was also observed. Finally, an overall reduction in the costs for patient management was demonstrated. Similar results were obtained in the two additional Centers of the Basilicata and Lazio Regions. CONCLUSIONS: An integrated management between hospital and territory allows optimization of the management of heart failure patients, with improvement of therapy and reduction in hospitalizations and management costs.

Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial.

BACKGROUND: The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown. We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients. METHODS: In this randomised open-label trial undertaken in 44 centres in Italy, 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were randomly assigned to a target systolic blood pressure of less than 140 mm Hg (usual control; n=553) or less than 130 mm Hg (tight control; n=558). After stratification by centre, we used a computerised random function to allocate patients to either group. Observers who were unaware of randomisation read electrocardiograms and adjudicated events. Open-label agents were used to reach the randomised targets. The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after randomisation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00421863. RESULTS: Over a median follow-up of 2.0 years (IQR 1.93-2.03), systolic and diastolic blood pressure were reduced by a mean of 23.5/8.9 mm Hg (SD 10.6/7.0) in the usual-control group and by 27.3/10.4 mm Hg (11.0/7.5) in the tight-control group (between-group difference 3.8 mm Hg systolic [95% CI 2.4-5.2], p<0.0001; and 1.5 mm Hg diastolic [0.6-2.4]; p=0.041). The primary endpoint occurred in 82 of 483 patients (17.0%) in the usual-control group and in 55 of 484 patients (11.4%) of the tight-control group (odds ratio 0.63; 95% CI 0.43-0.91; p=0.013). A composite cardiovascular endpoint occurred in 52 (9.4%) patients in the usual-control group and in 27 (4.8%) in the tight-control group (hazard ratio 0.50, 95% CI 0.31-0.79; p=0.003). Side-effects were rare and did not differ significantly between the two groups. INTERPRETATION: Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension. FUNDING: Boehringer-Ingelheim, Sanofi-Aventis, Pfizer.

Prognostic value of serial electrocardiographic voltage and repolarization changes in essential hypertension: the HEART Survey study.

BACKGROUND: The interpretation of serial electrocardiographic (ECG) changes in hypertensive subjects is uncertain. We tested the hypothesis that serial changes in repolarization and voltage are independent determinants of outcome. METHODS: The Hypertrophy at ECG And its Regression during Treatment (HEART) Survey was a prospective observational study performed at 61 centers. We studied 711 subjects with hypertension and ECG left-ventricular hypertrophy (LVH) at entry. Tracings from 496 subjects at entry and one or more visits during follow-up were available for central reading. RESULTS: The prevalence of ECG LVH progressively decreased by 49.6% at 3 years. The crude rate of a prespecified primary composite end point of cardiovascular events was 4.17 per 100 subjects per year (95% confidence interval [CI], 3.27 to 5.33). We used Cox regression models of ECG LVH indexes as time-varying covariates at baseline and at follow-up. Time-varying LVH, defined as an absence of ST-T alterations ("strain"), was associated with a lower event rate hazard ratio (HR), 0.47; 95% CI, 0.28 to 0.78; P = .0035), whereas the LVH changes defined in terms of ECG voltages did not achieve significance (HR, 0.91; 95% CI, 0.74 to 1.13; P = .39). The crude event rate in subjects with versus without in-treatment ST-T alterations on the last available ECG before the event or before censoring was 8.38 versus 3.17 per 100 subjects per year (P < .0001). CONCLUSIONS: In this study of subjects with hypertension and ECG LVH at entry, serial changes in repolarization significantly predicted the prognosis, independent of voltage change (which was not significantly predictive in this study). The persistence or new development of ST-T alterations identifies subjects at very high risk of cardiovascular events.

Ambulatory blood pressure monitoring early after acute myocardial infarction: development of a new prognostic index.

OBJECTIVES: The aim of our study was to assess the possible role of a prognostic index based on ambulatory blood pressure monitoring in a large cohort of patients with recent myocardial infarction. METHODS: The study population included 1335 consecutive patients admitted for ST elevation myocardial infarction and discharged alive from 48 Italian hospitals participating in the multicentric IMPRESSIVE (Infarto Miocardico, Pressione arteriosa e frequenza cardiaca. Studio Italiano di Valutazione Epidemiologica) study. Ambulatory blood pressure monitoring was performed 3 weeks after discharge, with a clinical follow-up of 12 months. End-points included cardiac death and new admission for heart failure. A prognostic index was obtained from the ambulatory blood pressure monitoring variables according to the formula: (220-age)-mean 24 h heart rate (m24hHR)+mean 24 h diastolic blood pressure (m24hDBP). RESULTS: Among many potential predictors only left-ventricular ejection fraction, creatinine levels, Killip class and the prognostic index were independently associated with events during the follow-up. In particular, higher values of the prognostic index were associated with a lower incidence of events, with an odds ratio of 0.958 (95% confidence intervals 0.943-0.974) and a 4% reduction in risk for each point of the prognostic index. Overall incidence of cardiac events was 6-fold higher in patients within the lowest quartile of the prognostic index (< or =148) compared with the other three quartiles (12 vs. 2, 1.4 and 2% respectively in the other three quartiles; P<0.0001). CONCLUSIONS: A simple prognostic index based on ambulatory blood pressure monitoring and age may be a useful tool in predicting cardiac death and heart failure in patients with recent myocardial infarction.

Regression of left ventricular hypertrophy and prevention of stroke in hypertensive subjects.

BACKGROUND: Left ventricular hypertrophy (LVH) is a risk marker for stroke and its regression confers protection from stroke. The relationship between serial LVH changes and risk of stroke has never been investigated in a mixed population of hypertensive subjects with and without LVH. METHODS: In this study, 880 initially untreated hypertensive subjects (mean age 48 years, office blood pressure (BP) 155/98 mm Hg; 24-h BP 137/87 mm Hg) underwent tests including echocardiography and 24-h ambulatory BP monitoring at entry and after a median of 3.5 years, still in the absence of cardiovascular events. RESULTS: Months or years after the follow-up study, 34 of these subjects developed a first cerebrovascular event (stroke in 21, transient ischemic attack in 13). Event rate (x 100 patients per year) was 0.25 among the subjects who never developed echocardiographic LVH or with regression of LVH, versus 1.16 among the subjects with lack of regression or new development of LVH (log-rank test: P = .00001). Serial electrocardiogram (ECG) changes failed to define groups at different risk. In a Cox analysis, the risk of cerebrovascular events was 2.8 times higher (95% CI: 1.18-6.69) in the subset with lack of regression or new development of LVH than in that with LVH regression or persistently normal LV mass. Such effect was independent of age (P = .001) and 24-h systolic BP (P = .003). CONCLUSIONS: In a mixed hypertensive population with and without LVH at entry, serial changes in the echocardiographic indexes of LVH predict subsequent cerebrovascular events independently of office and ambulatory BP and other individual risk factors.

Plant uncoupling protein in mitochondria from aged-dehydrated slices of Jerusalem artichoke tubers becomes sensitive to superoxide and to hydrogen peroxide without increase in protein level.

We investigated the occurrence of the plant Uncoupling Protein (UCP) in mitochondria isolated from both fresh (f-JAM) and aged-dehydrated (a-d-JAM) slices of Jerusalem artichoke tubers (Helianthus tuberosus L.). The presence of UCP was shown by immunological analysis and its function was investigated by measuring the decrease of the mitochondrial membrane potential due to linoleic acid (LA) and its inhibition by purine nucleotides under conditions in which the adenine nucleotide translocator (ANT) was inhibited by atractyloside (Atr). f-JAM and a-d-JAM had the same protein content, but differed from one another with respect to purine nucleotide inhibition, substrate specificity, and sensitivity to ROS. Hydrogen peroxide and superoxide anion, generated in situ by xanthine plus xanthine oxidase, caused a significant increase in the UCP function in a-d-JAM, but not in f-JAM. This occurred in a manner sensitive to ATP, but not to Atr, thus showing that ANT has no role in the process. The dependence of the rate of membrane potential decrease on increasing LA concentrations, either in the absence or the presence of ROS, showed a sigmoidal saturation both in f-JAM and a-d-JAM. However, addition of ROS in a-d-JAM resulted in about 40% increase of the Vmax value, with no change in the K0.5 (about 20 microM), whereas in f-JAM no effect on either the Vmax or K0.5 (about 28 microM) was found. Furthermore, a decreased ROS production as a result of LA addition was found in both f-JAM and a-d-JAM, the effect being more marked in a-d-JAM.

[Distribution of the global cardiovascular risk in the Italian population: results from the cardiovascular epidemiologic observatory]. / Distribuzione del rischio cardiovascolare globale nella popolazione italiana: risultati dell'Osservatorio Epidemiologico Cardiovascolare.

BACKGROUND: The aim of this study was to assess the 10-year cardiovascular risk categories using risk chart, recently set up by the National Institute of Health in the population examined by the Cardiovascular Epidemiologic Observatory. METHODS: 3745 men and 3664 women aged 40-69 years were classified into five risk categories (< 5 %; 5-10%; 10-15%; 15-20%; > or = 20%) taking into account age, smoking habit, history of diabetes, systolic blood pressure, serum cholesterol and excluding those already under treatment for hypertension and hypercholesterolaemia or experienced a previous major cardiovascular event (1937 persons: 955 men, 982 women). RESULTS: Proportion of people estimated at risk in 10 years > or = 20% is minimal in the youngest age range, increases in adulthood, duplicates in smokers and is higher in diabetics. In non-diabetic men that proportion varies between 3.4% in non-smokers and 5.6% in smokers. All women at risk are already under specific treatment. CONCLUSIONS: Cardiovascular Epidemiologic Observatory data allowed to assess the expected proportion of individuals at risk in 10 years > or = 20%. Besides attention to high-risk individuals, preventive measures supporting a healthier lifestyle in the general population must be adopted, considering that it will produce the greatest number of events.

[Diabetes in Italy: a public health problem]. / Il diabete in Italia: un problema di sanità pubblica.

BACKGROUND: Type 2 diabetes is the most frequent form of diabetes in the adult population and is associated with an increasing risk of cardiovascular diseases. The objective of this study was to describe the prevalence and the state of control in an Italian population sample examined within the Osservatorio Epidemiologico Cardiovascolare study. METHODS: The sample of this study consisted in 8972 subjects, men and women aged 35-74 years. A fasting capillary blood glucose > or = 126 mg/dl or being on antidiabetic treatment were the criteria used to define diabetes, while a fasting capillary blood glucose < 140 mg/dl was considered to represent effective treatment (controlled diabetes) in treated patients. RESULTS: Diabetes was present in 8.4% of men and 6% in women. The prevalence of glucose intolerance was 8.2% in men and 4.3% in women. Only 50.7% of diabetic men and 56.5% of diabetic women knew about their disease; among these people, 21% was on treatment with oral antidiabetics and/or insulin. Such a therapy was effective in 39.5% of the treated cases. CONCLUSIONS: The prevalence of diabetes as well as glucose intolerance was greater in men and in the regions of the Center and South of Italy. The state of control of diabetes cannot be considered satisfactory; women and older age groups, when prevention strategies are less important, appear to be under better care.

Isolated durum wheat and potato cell mitochondria oxidize externally added NADH mostly via the malate/oxaloacetate shuttle with a rate that depends on the carrier-mediated transport.

We investigated whether and how mitochondria from durum wheat (Triticum durum Desf.) and potato (Solanum tuberosum), isolated from etiolated shoots and a cell suspension culture, respectively, oxidize externally added NADH via the mitochondrial shuttles; in particular, we compared the shuttles and the external NADH dehydrogenase (NADH DHExt) with respect to their capacity to oxidize external NADH. We found that external NADH and NADPH can be oxidized via two separate DHExt, whereas under conditions in which the activities of NAD(P)H DHExt are largely prevented, NADH (but not NADPH) is oxidized in the presence of external malate (MAL) and MAL dehydrogenase, in a manner sensitive to several non-penetrant compounds according to the occurrence of the MAL/oxaloacetate (OAA) shuttle. In durum wheat mitochondria and potato cell mitochondria, the rate of NADH oxidation was limited by the rate of a novel carrier, the MAL/OAA antiporter, which is different from other carriers thought to transport OAA across the mitochondrial membrane. No NAD(P)H oxidation occurred arising from the MAL/Aspartate and the alpha-glycerophosphate/dihydroxyacetonphosphate shuttles. We determined the kinetic parameters of the enzymes and the antiporter involved in NADH oxidation, and, on the basis of a kinetic analysis, we showed that, at low physiological NADH concentrations, oxidation via the MAL/OAA shuttle occurred with a higher efficiency than that due to the NADH DHExt (about 100- and 10-fold at 1 microm NADH in durum wheat mitochondria and in potato cell mitochondria, respectively). The NADH DHExt contribution to NADH oxidation increased with increasing NADH concentration.

Hypertrophy at ECG and its regression during treatment survey (HEART survey). Rationale, design and baseline characteristics of patients.

BACKGROUND: Left ventricular hypertrophy (LVH) detected at electrocardiography (ECG) is a predictor of an increased cardiovascular risk in essential hypertension. However, uncertainty remains concerning the reproducibility of ECG LVH and the prognostic relevance of its regression over time in hypertension. The aim of this study was to determine the prognostic value of baseline ECG LVH and its serial changes in a large cohort of hypertensive patients. METHODS: The Hypertrophy at ECG and its Regression during Treatment Survey (HEART Survey) is a prospective observational study conducted in 66 Italian centers. Inclusion criteria are essential hypertension with ECG LVH defined by the Perugia score (Cornell voltage criteria and/or a typical left ventricular "strain" pattern and/or a Romhilt-Estes score > or = 5 points) in subjects aged 45-84 years. The treatment of hypertension and other risk factors accords with current guidelines and is individually tailored. ECG is recorded twice at entry and periodically repeated over a 4-year follow-up period. Expert readers (unaware of the clinical findings) classify ECG. The incidence of major cardiovascular events in relation to baseline ECG and its changes over time are assessed, together with the reproducibility in the two baseline recordings. Overall, 708 patients aged 64 +/- 9 years have been enrolled in centers from northern (27%), central (32%) and southern (41%) Italy. Their baseline characteristics are presented. Follow-up is ongoing. CONCLUSIONS: The HEART Survey will examine the prognostic value of baseline ECG LVH and of its regression over time in a wide population of hypertensive patients.

Prognosis of inappropriate left ventricular mass in hypertension: the MAVI Study.

To evaluate the prognostic impact of left ventricular (LV) mass exceeding individual needs to compensate hemodynamic load, the percentage of excess of echocardiographic LV mass in relation to individual ideal value predicted by gender, stroke work, and height (in meter(2.7)) from a reference population was assessed in 1019 white hypertensives (627 women [24% obese] and 392 men [17% obese, P<0.02 versus women]) without prevalent cardiovascular disease or type 1 diabetes, from the Italian multicenter, prospective study MAVI. Low LV mass (<73% of predicted) was found in 36 patients (3.5%), 661 had appropriate LV mass, and 322 (37%) had inappropriate LV mass. During follow-up (35+/-11 months), 52 fatal or nonfatal primary cardiovascular events occurred. Age, systolic blood pressure, and LV mass as a percentage of the predicted value were significant predictors of cardiovascular events (all P<0.01), independently of gender, glycemia, antihypertensive treatments, and body mass index, even in subgroups with or without LV hypertrophy. Survival analysis showed that cardiovascular risk increased stepwise from the lowest to the highest quintile of LV mass as a percentage of predicted value (P<0.01). The excess LV mass showed incremental prognostic value compared with assessment of traditional LV mass (P<0.01). Thus, inappropriate LV mass predicts a risk of cardiovascular events, independently of risk factors, and remains a significant predictor of risk either in the presence or in the absence of traditionally defined LV hypertrophy.

Risk of cardiovascular disease in relation to achieved office and ambulatory blood pressure control in treated hypertensive subjects.

OBJECTIVE: We investigated the prognostic impact of 24-h blood pressure control in treated hypertensive subjects. BACKGROUND: There is growing evidence that ambulatory blood pressure improves risk stratification in untreated subjects with essential hypertension. Surprisingly, little is known on the prognostic value of this procedure in treated subjects. METHODS: Diagnostic procedures including 24-h noninvasive ambulatory blood pressure monitoring were undertaken in 790 subjects with essential hypertension (mean age 48 years) before therapy and after an average follow-up of 3.7 years (2,891 patient-years). RESULTS: At the follow-up visit, 26.6% of subjects achieved adequate office blood pressure control (<140/90 mm Hg), and 37.3% of subjects achieved adequate ambulatory blood pressure control (daytime blood pressure <135/85 mm Hg). Months or years after the follow-up visit, 58 patients suffered a first cardiovascular event. Event rate was lower (0.71 events/100 person-years) among the subjects with adequate ambulatory blood pressure control than among those with higher blood pressure levels (1.87 events/100 person-years) (p = 0.0026). Ambulatory blood pressure control predicted a lesser risk for subsequent cardiovascular disease independently of other individual risk factors (RR 0.36; 95% confidence intervals: 0.18 to 0.70; p = 0.003), including age, diabetes and left ventricular hypertrophy. Office blood pressure control was associated with a nonsignificant lesser risk of subsequent events (RR 0.63; 95% confidence intervals: 0.31 to 1.31; p = NS). In-treatment ambulatory blood pressure was more potent than pre-treatment blood pressure for prediction of subsequent cardiovascular disease. CONCLUSIONS: Ambulatory blood pressure control is superior to office blood pressure control for prediction of individual cardiovascular risk in treated hypertensive subjects.