G Leonetti

I.R.C.C.S. Istituto Auxologico Italiano, Milano, Lombardy, Italy

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Publications (262)733.32 Total impact

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    ABSTRACT: Background and aims The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes. Methods and results: A total of 2,429 patients (mean age 62±11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73m2 or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95%CI 1.03-1.18; p=0.0060; OR 1.28, 95%CI 1.15-1.42; p <0.0001). These associations were stronger in patients without diabetes and with normal renal function. Conclusions Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 08/2014; · 3.52 Impact Factor
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    ABSTRACT: The results of the Hypertension in the Very Elderly Trial showed positive benefits from blood pressure-lowering treatment in those aged 80 and over.
    Journal of hypertension. 07/2014; 32(7):1478-1487.
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    ABSTRACT: AIM:: The aim of this study is to evaluate the differences in the prevalence of chronic kidney disease (CKD) and of cardiovascular risk factors and diseases between men and women participating in the Italy Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease (I-DEMAND) study. METHODS:: This is an observational, cross-sectional, multicenter study aimed at assessing prevalence and correlates of CKD among Italian hypertensive patients attending out-patient referral clinics. CKD was defined as glomerular filtration rate (GFR) less than 60 ml/min per 1.73 m [Modification of Diet in Renal Disease (MDRD) study equation and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation] and/or urine albumin-to-creatinine ratio of at least 2.5 mg/mmol in men and of at least 3.5 mg/mmol in women or both. Left-ventricular hypertrophy (LVH) was diagnosed by either ECG or echocardiography. RESULTS:: A total of 3558 study patients with renal data available were considered for this analysis: mean age was 61 ± 4 years and 37% had diabetes mellitus. Female patients (n = 1636, 46%) were older, with a greater prevalence of obesity and lower prevalence of smoking. The prevalence of concomitant coronary artery and peripheral artery diseases, but not of hypertension, diabetes mellitus, or heart failure, was lower in women than in men. The overall prevalence of albuminuria (21 vs. 32%; P = 0.001) and of microalbuminuria (16 vs. 23%; P = 0.001) was lower in women than in men. In women the prevalence of a reduced GFR estimated by both MDRD (33 vs. 21%; P = 0.001) and CKD-EPI equations (32 vs. 23%; P = 0.001) was higher than in men. CKD prevalence was similar in women and men (44 vs. 41%; P = 0.095 and 43 vs. 43%; P = 0.475, respectively, when MDRD and CKD-EPI eGFR estimations were used). The prevalence of LVH (diagnosed by either ECG or echocardiography) was similar in men and women (18 vs. 20%; P = 0.12).The main independent determinants of CKD were age, glycemia, uricemia, pulse pressure, hypertension duration, and previous cardiovascular diseases in men, and increasing age, glycemia, uricemia, pulse pressure, and a lower BMI in women. CONCLUSION:: Renal abnormalities are present in a significant number of female hypertensive patients attending hypertension clinics. Prevalence of reduced eGFR and of microalbuminuria, associated risk factors, and clinical conditions are different between men and women, suggesting the need to develop specific therapeutic strategies to prevent renal dysfunction and reduce associated morbidity and mortality.
    Journal of Hypertension 11/2012; · 4.22 Impact Factor
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    ABSTRACT: Objective: We have assessed the influence of gender and age on the main outcome results of the Hypertension Optimal Treatment (HOT) study. Design and interventions: The aims of the HOT study were to study the relationship between three levels of target office diastolic blood pressure (BP) (≤ 90, ≤ 85 or ≤ 80 mmHg) and cardiovascular (CV) events in hypertensive patients, and to examine the effects of 75 mg acetylsalicylic acid (ASA) daily versus placebo. Setting: Outpatient clinical trial in 26 countries. Patients: A total of 18 790 patients (mean age 61.5 years, range 50–80) were randomized and followed for an average of 3.8 years until 71 051 patient-years and 683 events had occurred. Main outcome measures: CV death, myocardial infarction (MI) and stroke. Results: There were significantly fewer MIs in those in the lower diastolic BP target groups (3.0 versus 1.2 and 1.7 MIs/1000 patient-years, P for trend = 0.034) in women (n = 8883), whereas the similar but smaller trend (4.1 versus 4.1 and 3.4 MIs/1000 patient-years) was not statistically significant in men nor in the subgroup analysis of younger and older subjects. The effect of ASA on preventing MI was not influenced by age <65 years (P = 0.02) or age >65 years (P = 0.04) but was influenced by gender (P = 0.38 in women and P = 0.001 in men, lowered by 42% corresponding to a reduction from 5.0 to 2.9 MIs/1000 patient-years). Conclusions: The data of this HOT study sub-analysis suggest somewhat differentiated optimal gender- and age- dependent effects of anti-hypertensive and anti-platelet therapies; lowering of diastolic BP to about 80 mmHg in hypertensive women and, in addition, the administration of 75 mg of ASA to well-treated hypertensive men appear to effectively reduce the most common cardiovascular complication, i.e. myocardial infarction, in patients with essential hypertension.
    Journal of Hypertension 07/2012; 18(5):629–642. · 4.22 Impact Factor
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    ABSTRACT: Metabolic syndrome (MS) and chronic kidney disease (CKD) are well-known, independent predictors of increased cardiovascular risk. Both conditions are fairly prevalent in the general population. The aim of this study was to assess the relationship between MS or its individual components and CKD in an Italian population of hypertensive patients with normal or mildly to moderately impaired renal function under specialist care. A total of 2,916 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were taken into consideration for this analysis. MS was defined according to the NCEP-ATP III criteria. CKD was defined as an estimated GFR (abbreviated MDRD equation) <60 ml/min/1.73m2 or as the presence of microalbuminuria (mean albumin-to-creatinine ratio =2.5 mg/mmol in men and =3.5 mg/mmol in women). MS was present in 59% of our study patients. The prevalence of microalbuminuria, reduced GFR and CKD was 26%, 25%, and 41%, respectively. Patients with MS had higher urinary albumin excretion (p<0.0001), lower GFR (p=0.0077), and a greater prevalence of CKD (p<0.0001), even after adjusting for age and gender. Multivariate logistic regression analysis revealed that MS was significantly associated with CKD, even after adjusting for several potential confounders including its individual components (OR 1.33, 95%CI 1.03-1.71, p=0.0268). The association between MS and CKD was stronger in nondiabetic patients. Renal abnormalities and MS are frequently associated in hypertensive patients under specialist care. This relationship is independent of several potential confounding factors including the components of MS.
    Journal of nephrology 04/2011; 25(1):63-74. · 2.02 Impact Factor
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    ABSTRACT: To report blood pressure control in the Hypertension in the Very Elderly Trial, a placebo-controlled trial of hypertensive (systolic blood pressure (SBP) 160-199 mm Hg, diastolic blood pressure (DBP) <110 mm Hg) participants over the age of 80 years, given treatment in three steps: indapamide slow release 1.5 mg alone, indapamide plus 2 mg perindopril and indapamide plus 4 mg perindopril. The difference in control between participants with combined systolic and diastolic hypertension (SDH, DBP90 mm Hg) and those with isolated systolic hypertension (ISH, DBP<90 mm Hg) is determined together with the effects of increments in the treatment regimen. At 2 years, the active treatment lowered blood pressure by 16.5/6.9 mm Hg more than that on placebo in participants with SDH and by 19.3/4.8 mm Hg more in those with ISH. The 2-year falls in pressure on placebo alone were 13.2/8.5 mm Hg in SDH and 8.2/1.5 mm Hg in ISH participants. With full titration of active treatment, 62% of SDH participants achieved goal SBP (<150 mm Hg) by 2 years and 71% of those with ISH. The corresponding results for DBP control (<80 mm Hg) were 40 and 78%. The addition of active perindopril 2 mg roughly doubled the percentage controlled, as did increasing to 4 from 2 mg. Blood pressure control was good with ISH and better than with SDH. The fall in SBP accounted for the observed 30% reduction in strokes, but the 21% reduction in total mortality and 64% reduction in heart failure were greater than predicted.
    Journal of human hypertension 03/2011; 26(3):157-63. · 2.80 Impact Factor
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    ABSTRACT: The kidney has been recognized as a sensor of cardiovascular risk. However, evaluation of urinary albumin excretion and estimated glomerular filtration rate is still too often overlooked in clinical practice. The I-DEMAND (Italy-Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease) study was designed to assess the prevalence of microalbuminuria and its clinical correlates among Italian hypertensive patients. A total of 4151 patients from 87 specialized care centres were included in the study. Overall, this study demonstrated that approximately one-half of the enrolled patients had chronic kidney disease, with albuminuria being present in one-quarter of the individuals. The presence of renal abnormalities was more prevalent in patients with concomitant cardiovascular risk factors. This article discusses the main results of the study and its potential implications in clinical practice.
    High Blood Pressure & Cardiovascular Prevention 03/2011; 18(1):31-6.
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    ABSTRACT: A reduced fall in nocturnal blood pressure (BP) (i.e. non-dipping) has been related to an increase in target organ damage and cardiovascular (CV) events. Numerous studies have shown that non-dipping is highly prevalent in patients with type 1 and 2 diabetes mellitus. In this paper we reviewed recent literature and our personal data on the prevalence and clinical correlates of abnormal diurnal BP rhythm in diabetic patients; in particular we examined the association of this condition with renal, cardiac, and vascular pre-clinical organ damage as well as CV prognosis. A consistent body of evidence based on cross-sectional and longitudinal studies indicates that the lack of the physiologic nocturnal fall in BP may be considered a true clinical trait, a reliable marker of preclinical CV and renal disease and an independent predictor of future CV events. Thus, in the diabetic setting ambulatory BP monitoring (ABPM) should be regarded as a pivotal tool for improving CV risk stratification and therapeutic interventions.
    Current diabetes reviews 03/2010; 6(2):111-5.
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    ABSTRACT: Italy Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease is an observational, cross-sectional, multicenter study aimed at determining prevalence and correlates of chronic kidney disease (CKD) among Italian hypertensive patients attending out-patient referral clinics. CKD was defined as glomerular filtration rate (GFR) less than 60 ml/min per 1.73 m (Modification of Diet in Renal Disease equation) or urine albumin to creatinine ratio of at least 2.5 mg/mmol in men and of at least 3.5 mg/mmol in women or both. Among 3534 study patients (mean age 61 years, 54% male patients, 37% diabetic patients), the prevalence of microalbuminuria, reduced GFR, and CKD was 27, 26, and 42%, respectively. Only 11% of patients had concomitant microalbuminuria and reduced GFR. Sex, smoking, systolic blood pressure, glucose, and GFR were the independent predictors of albumin to creatinine ratio, whereas sex, age, history of cardiovascular diseases, uric acid, abdominal obesity, and albumin to creatinine ratio were more closely related to GFR. The presence of CKD was associated with older age, smoking, higher systolic and pulse pressure levels, impaired fasting glucose, hyperuricemia, and previous cardiovascular disease. Furthermore, CKD was not only associated with a greater use of renin-angiotensin system-inhibiting, lipid-lowering and antiplatelet drugs but also with inadequate blood pressure control. Renal abnormalities are found in a significant number of hypertensive patients. CKD occurs more often in older patients and in those with associated metabolic risk factors or clinical conditions. These results suggest the need to improve awareness of the role of renal damage as a component of global risk and to develop appropriate therapeutic strategies to reduce morbidity and mortality in this specific subgroup of patients.
    Journal of Hypertension 11/2009; 28(1):156-62. · 4.22 Impact Factor
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    ABSTRACT: In the past years, several risk charts have been created to increase the accuracy of cardiovascular risk stratification. The most widely used and validated algorithms do not included target organ damage as risk prediction. The aim of the present study was to evaluate whether preclinical renal damage is associated with cardiovascular diseases independently of individual risk profile assessed by risk charts. The study population was that of Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease, a large observational study conducted on hypertensive patients in Italy. The Framingham Risk Score (FRS), Systematic COronary Risk Estimation (SCORE) and Progetto Cuore Risk Score (Progetto Cuore RS) were computed in each eligible patient. Chronic kidney disease was defined by the presence of albuminuria or by a reduction of glomerular filtration rate. Study participants were categorized to have low, medium and high risk according to the tertiles of the three charts. Prevalence of total cardiovascular diseases progressively and significantly increased according to the degrees of risk assessed by the three charts, the highest prevalence being in participants with a high-risk profile (both high and medium vs. low risk <0.01 for FRS, SCORE and Progetto Cuore RS). The presence of chronic kidney disease was associated with total cardiovascular diseases, independently of FRS (odds ratio 1.64, 95% confidence interval 1.33-2.02, P < 0.001), SCORE (odds ratio 1.55, 95% confidence interval 1.21-1.98, P < 0.001) and Progetto Cuore RS (odds ratio 1.59, 95% confidence interval 1.22-2.07, P < 0.001). Moreover, inclusion of renal damage in the logistic model significantly increased the accuracy of the FRS (P < 0.05), SCORE (P < 0.01) and Progetto Cuore RS (P < 0.01) to identify patients with overt cardiovascular diseases. Identification of patients with preclinical renal damage should be encouraged in the hypertension cardiovascular risk stratification setting in order to achieve a more accurate individual risk computation. The presence of renal damage could improve cardiovascular risk prediction over the widely used risk stratification charts.
    Journal of Hypertension 10/2009; 28(2):251-8. · 4.22 Impact Factor
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    ABSTRACT: Objective. To compare the antihypertensive effect of treatment with zofenopril vs candesartan by office and ambulatory blood pressure (BP). Design and methods. Following a 2‐week wash‐out from previous treatment, 236 grade I–II primary hypertensive patients were randomized double‐blind to 12 weeks treatment with zofenopril 30 mg or candesartan 8 mg od. After 4 weeks, treatment was doubled in responder non‐normalized (office systolic BP140 mmHg and office diastolic BP reduction 10 mmHg) or non‐responder patients (office systolic BP140 mmHg and office diastolic BP reduction <10 mmHg). Following a further 4 weeks, non‐responder or non‐normalized patients were withdrawn. Results. In the intention‐to‐treat population, office systolic BP and diastolic BP reductions after 12 weeks of treatment were similar between the two groups (zofenopril: 21±11/15±8 mmHg, n = 114 vs C: 20±11/15±7 mmHg, n = 122; p = NS). In the 163 patients of the per‐protocol population, office BP dropped by 22±11/15±8 mmHg (zofenopril) and 20±10/15±7 mmHg (candesartan; p = NS). Also 24‐h ambulatory BPs were equally reduced by zofenopril and candesartan ( 7±13/5±8 mmHg vs 7±12/5±8 mmHg; p = NS). The trough‐to‐peak ratio and smoothness index were not significantly different between zofenopril and candesartan. Tolerability of both drugs was good. Conclusions. Monotherapy with zofenopril and candesartan similarly reduced office and 24‐h BPs. Since almost 90% of patients were normalized by either zofenopril or candesartan, this result supports the importance of considering low‐ or high‐dose monotherapies as initial treatment for most hypertensive patients of mild degree.
    07/2009; 15(s1):18-26.
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    ABSTRACT: Renal abnormalities are strongly associated with cardiac damage in essential hypertension. Detection of preclinical cardiac and renal abnormalities is a key clinical step in hypertension management. This study investigated the relationship between ECG abnormalities and microalbuminuria (MAU) in hypertensive patients without overt cardiovascular disease. This relationship, in fact, has never been extensively studied. The study population was that of Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease, a large observational study including 4121 hypertensive patients in Italy. Patients with overt cardiovascular diseases were excluded from the present analysis. ECGs were centrally read and urinary albumin/creatinine ratio was carefully assessed. Chronic kidney disease was defined by the presence of albuminuria or by a reduction of glomerular filtration rate. The presence of ECG abnormalities was significantly and directly associated with chronic kidney disease [odds ratio (OR) 1.66, 95% confidence interval (CI) 1.32-2.07, P<0.001], particularly with MAU (OR 1.81, 95% CI 1.39-2.36, P<0.001). Main selected ECG abnormalities were also significantly associated with MAU [rhythm abnormalities (OR 2.94, 95% CI 1.77-4.88, P<0.001), intraventricular conduction defects (OR 1.95, 95% CI 1.32- 2.87, P<0.01), ventricular repolarization alterations (OR 1.84, 95% CI 1.26-2.70, P<0.01) and left-axis deviation (OR 1.87, 95% CI 1.26-2.79, P<0.01)]. After adjustment for confounders, an abnormal ECG and all the main ECG abnormalities remained significantly associated with MAU. This is the first large and systematic analysis of the relationship between detailed ECG abnormalities and MAU/chronic kidney disease in hypertensive patients without overt cardiovascular diseases. We report a significant and independent relationship between the presence of ECG abnormalities and renal damage in a preclinical stage of hypertension. Identification of ECG abnormalities in hypertension should prompt physicians to careful detection for renal damage, also in order to achieve an accurate risk stratification.
    Journal of Hypertension 02/2009; 27(2):410-7. · 4.22 Impact Factor
  • Giornale italiano di cardiologia (2006) 07/2008; 9(6):427-54.
  • Gastone Leonetti, Cesare Cuspidi
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    ABSTRACT: Numerous epidemiological studies have shown that the lower the blood pressure the lower the cardiovascular risk. On the other hand, intervention studies with antihypertensive agents in patients with systolic-diastolic or isolated systolic hypertension have shown that the antihypertensive treatment decreases the incidence of cardiovascular events: however it is still undefined which is the better blood pressure goal to reach during antihypertensive therapy. Observational studies and secondary analysis of large randomized trials have shown that treated hypertensive patients with diastolic values below some critical levels have a higher incidence of deaths and cardiovascular events. Studies on different populations evaluated with different protocols have given non-uniform results and many hypothesis have been suggested as causes of low diastolic pressure: 1) excessive antihypertensive treatment, 2) decreased compliance of aorta and large arteries and 3) clinical signs of a concomitant disease. Different studies suggest that diastolic blood pressure values lower than 70-80 mmHg, independently from the responsible physiopathological mechanisms, may rise the risk of cardiovascular events. Therefore, from the clinical point of view, extreme caution in the titration of the antihypertensive therapy for elevated systolic values when the range of diastolic blood pressure is below 70-80 mmHg.
    Recenti progressi in medicina 05/2008; 99(4):191-9.
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    ABSTRACT: Left ventricular hypertrophy (LVH) assessed by echocardiography has a relevant impact in clinical decision making in hypertensive patients. We investigated the precision and accuracy of hypertensive LVH determination in current clinical practice by a regional-based survey. The study included 211 patients with essential hypertension consecutively attending six hospital outpatient hypertension clinics in the northern Italian region of Lombardy; all subjects had undergone an echocardiographic examination for hypertension-related problems in a non-academic or research ultrasound laboratory within 2 years. The original echocardiographic report was examined to ascertain whether the diagnosis of LVH was based on calculation of left ventricular (LV) mass according to validated formulae and indexed to body size (primary outcome) and whether LV geometrical patterns and indices of diastolic function were provided (secondary outcome). A total of 211 echocardiograms performed by 120 physicians operating in 73 different hospital and out-of-hospital ultrasound laboratories were collected. Absolute LV mass, LV mass index and relative wall thickness were calculated in 45.5%, 24.6% and 12.3% of the cases, respectively. Parameters of LV diastolic filling were measured in two-thirds of the cases and estimation of E/A ratio was provided by less than 20% of the examinations. This study shows that a large majority of echocardiographic examinations, routinely performed in hypertensive subjects in order to detect cardiac damage, do not report qualifying data on LV mass, LV geometry and diastolic function. These results indicate that a quantitative assessment of LVH and LV function is rarely provided in clinical practice.
    Blood Pressure 02/2008; 17(2):124-8. · 1.39 Impact Factor
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    ABSTRACT: A previous analysis of the ForLife study demonstrated a high estimated risk of stroke, poor blood pressure control and higher cardiovascular risk. Data from a subsequent visit within 6 months, to evaluate the impact of systematic stroke risk assessment, are reported. Between February and July 2003, 1800 general practitioners (GPs) recruited a total of 12,792 (7512 untreated and 5280 treated) patients with hypertension. Blood pressure values were assessed in the whole study population, and for different demographic and clinical features in two visits within 6 months. The data were recorded into a Framingham-based stroke risk score and computed using a risk calculator. Between the two visits the percentage of patients with controlled blood pressure (< 140/90 mmHg) increased substantially in all subgroups, being greater in patients who were not treated at baseline. Among initially treated patients, the greater control of blood pressure involved both diastolic and systolic values. The percentage of patients with diabetes whose blood pressure levels were less than 130/80 mmHg also increased at the second visit. Between the two visits the estimated stroke risk score showed a reduction, with a significant shift of patients from high to intermediate and low-risk categories. This reduction involved all subgroups, including patients with diabetes and left ventricular hypertrophy. The present large-scale observational study demonstrates that the assessment of stroke risk and increased awareness of stroke risk factors by GPs is associated with improved blood pressure control, reduced cardiovascular risk profile and a prompt reduction in the 10-year estimated risk of stroke.
    Journal of Hypertension 12/2007; 25(12):2390-7. · 4.22 Impact Factor
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    ABSTRACT: A number of patients with chronic heart failure (CHF) have diastolic but not systolic dysfunction. This occurs particularly in the elderly and in hypertension, but the prevalence of diastolic dysfunction in elderly hypertensives without CHF has never been investigated systematically. The Assessment of PRevalence Observational Study of Diastolic Dysfunction (APROS-diadys) project was a cross-sectional observational study on elderly (age >/= 65 years) hypertensives without systolic dysfunction [left ventricular ejection fraction (LVEF) >/= 45%] consecutively attending hospital outpatient clinics in Italy, in order to establish the prevalence of echocardiographic signs of diastolic dysfunction according to various criteria, and to correlate them with a number of demographic and clinical characteristics. Primary criteria for diastolic dysfunction was an E/A ratio (ratio between transmitral peak velocities of E and A waves) < 0.7 or > 1.5 on echocardiographic Doppler examination. Secondary criteria were: E/A < 0.5 and deceleration time (DT) > 280 ms, or isovolumic relaxation time (IVRT) > 105 ms or pulmonary vein (PV) peak systolic/peak diastolic flow (S/D) ratio > 2.5 or PV atrial retrograde flow (PV A) > 35 cm/s. Throughout Italy, 27 447 patients were screened in 107 clinics, with 24 141 excluded according to protocol. Among the remaining 3336 patients, 754 (22.6%) had signs of CHF. After exclusion of 37 protocol violators, 2545 patients (49.0% men, mean age 70.3 years, 95.4% under antihypertensive treatment) were studied ultrasonographically. Diastolic dysfunction (primary criteria) was found in 649 (25.8%) patients. Multiple logistic regression analysis found age, gender, left ventricular mass, systolic and pulse pressures and midwall shortening fraction as significant covariates. Using secondary criteria, the prevalence of diastolic dysfunction was higher (45.6%), mostly because of IVRT > 105 ms or PVA flow > 35 cm/s. CHF and diastolic dysfunction are highly prevalent in elderly hypertensives attending hospital clinics.
    Journal of Hypertension 10/2007; 25(10):2158-67. · 4.22 Impact Factor
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    ABSTRACT: It has been suggested that low diastolic blood pressure (BP) while receiving antihypertensive treatment (hereinafter called on-treatment BP) is harmful in older patients with systolic hypertension. We examined the association between on-treatment diastolic BP, mortality, and cardiovascular events in the prospective placebo-controlled Systolic Hypertension in Europe Trial. Elderly patients with systolic hypertension were randomized into the double-blind first phase of the trial, after which all patients received active study drugs (phase 2). We assessed the relationship between outcome and on-treatment diastolic BP by use of multivariate Cox regression analysis during receipt of placebo (phase 1) and during active treatment (phases 1 and 2). Rates of noncardiovascular mortality, cardiovascular mortality, and cardiovascular events were 11.1, 12.0, and 29.4, respectively, per 1000 patient-years with active treatment (n = 2358) and 11.9, 12.6, and 39.0, respectively, with placebo (n = 2225). Noncardiovascular mortality, but not cardiovascular mortality, increased with low diastolic BP with active treatment (P < .005) and with placebo (P < .05); for example, hazard ratios for lower diastolic BP, that is, 65 to 60 mm Hg, were, respectively, 1.15 (95% confidence interval, 1.00-1.31) and 1.28 (95% confidence interval, 1.03-1.59). Low diastolic BP with active treatment was associated with increased risk of cardiovascular events, but only in patients with coronary heart disease at baseline (P < .02; hazard ratio for BP 65-60 mm Hg, 1.17; 95% confidence interval, 0.98-1.38). These findings support the hypothesis that antihypertensive treatment can be intensified to prevent cardiovascular events when systolic BP is not under control in older patients with systolic hypertension, at least until diastolic BP reaches 55 mm Hg. However, a prudent approach is warranted in patients with concomitant coronary heart disease, in whom diastolic BP should probably not be lowered to less than 70 mm Hg.
    Archives of Internal Medicine 09/2007; 167(17):1884-91. · 11.46 Impact Factor
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    ABSTRACT: . Sartorio A, Perrero S, Conti A, Bragato R, Malfatto G, Leonetti G, Faglia G. (Laboratorio Sperimentale di Ricerche Endocrinologiche, Istituto AuxoIogico Italiano, Milano, Italy). Adults with childhood-onset growth hormone deficiency: effects of growth hormone treatment on cardiac structure.Objectives: To evaluate the effects of growth hormone deficiency (GHD) and of growth hormone (GH) therapy on cardiac structure in adults with child-hood-onset GHD.Settiig: Out-patient clinic in the Italian Institute for Auxology, Milan.Subjects: Eight adults with childhood-onset GHD and eight healthy controls, matched for sex, age, exercise and body mass index.Interventions: Recombinant GH (Saizen Serono, Italy), administered in a conventional dose of 0.5 IU kg-1 week-1 for 6 months.Main outcome measures: Cardiac structure parameters, evaluated by two-dimensional, M-mode and Doppler echocardiograms, and stress test, by means of a modified Bruce protocol with a bicycle ergometer, were determined before and after 6 months GH therapy.Results: Before treatment, mean (±SE) intraventricular septal thickness (IVST: 7.1 ± 0.2 mm), LV posterior wall thickness (LVPT: 5.2± 0.1 mm), LV mass(LVM: 94.6 ± 5.0 g), LV massindex (LVM/body surface area, LVMI: 65.1 ± 3.0 g m-2) and left ventricular end-diastolic diameter (LVED 41.4 ± 0.6 mm) of patients were significantly lower (P< < 0.01) than in controls, whilst LV end-systolic diameter (LVES) of patients (25.5 ± 0.7 mm) was similar to controls (27.5 ± 0.7). GH treatment significantly (P < 0.01) increased LWT (6.8 ± 0.2 mm), LVM (111.6 ± 4.6 g) and LVMI (80.5 ± 3.5 gm-2): no sigdcant changes were observed in LVED, LVES and IVST values. The stress test showed a significant improvement of cardiac performance, as demonstrated by the reduction of blood pressure x heart rate product at the same workload (basal: 32722.5 ± 897.4 vs. after: 25574.6 ± 439.7).Conclusions: GH plays a role in the maintenance of a normal cardiac structure in adulthood. The present study suggests that GH treatment might be able to improve the cardiac structure of patients with childhood-onset GHD.
    Journal of Internal Medicine 01/2007; 241(6):515-520. · 6.46 Impact Factor
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    ABSTRACT: Background: QT dispersion (QTd) on the ECG is thought to reflect the temporal and spatial inhomogeneity of repolarization in the underlying myocardium. In myocardial infarction, ischemia, and long QT syndromes, an increased QTd is associated with a propensity for malignant ventricular arrhythmias and sudden cardiac death. We investigated this feature of the repolarization process in subjects with frequent ventricular arrhythmias and structurally normal hearts.Methods: Forty-nine patients referred for frequent, nonsustained ventricular arrhythmias (45 ± 14 years, ×± SD, 61% female) had normal ventricular dimensions and function, no late potentials, and normal ECG. They were compared with 30 controls (42 ± 13 years, 50% female). QTd was measured as the difference between the longest and the shortest QT in the six precordial leads at a paper speed of 50 mm/s.Results: In patients, QTc was similar to that of controls: 395 ± 21 versus 386 ± 20. However, QTd was greater: 49 ± 20 ms versus 32 ± 14 ms, P < 001. Moreover, 18 patients (36%) had QTd exceeding 60 ms—a value superior to the mean normal value of 2 SD—compared to only 1 control (3%) (P < 0.01). Finally, patients with more frequent ventricular arrhythmias had larger QTd.Conclusions: In patients with frequent nonsustained ventricular arrhythmias and otherwise normal hearts, QT interval dispersion is increased. We speculate that, instead of representing a specific electrophysiological substrate of arrhythmias, QT dispersion in this specific population could result from arrhythmias themselves through a possible mechanoelectrical feedback.
    Annals of Noninvasive Electrocardiology 10/2006; 5(2):119 - 124. · 1.08 Impact Factor

Publication Stats

5k Citations
733.32 Total Impact Points


  • 1996–2014
    • I.R.C.C.S. Istituto Auxologico Italiano
      Milano, Lombardy, Italy
  • 2011
    • Azienda Ospedaliera Universitaria San Martino di Genova
      Genova, Liguria, Italy
  • 2009–2011
    • Università degli Studi di Genova
      Genova, Liguria, Italy
    • Sapienza University of Rome
      • Department of Clinical and Molecular Medicine
      Roma, Latium, Italy
  • 2000–2005
    • Università degli Studi di Milano-Bicocca
      Milano, Lombardy, Italy
    • University of Bologna
      • Institute of Genetic Medicine
      Bologna, Emilia-Romagna, Italy
  • 1999–2004
    • IRCCS Multimedica
      Milano, Lombardy, Italy
  • 1970–2004
    • University of Milan
      • Department of Internal Medicine
      Milano, Lombardy, Italy
  • 1998
    • University of Leuven
      Louvain, Flanders, Belgium
  • 1997
    • Università degli Studi di Brescia
      Brescia, Lombardy, Italy
  • 1995
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
    • Università degli Studi del Sannio
      Benevento, Campania, Italy
  • 1994
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 1988
    • Politecnico di Milano
      Milano, Lombardy, Italy