Gianpaolo Reboldi | University of Perugia (original) (raw)
Papers by Gianpaolo Reboldi
Polskie Archiwum Medycyny Wewnetrznej-polish Archives of Internal Medicine, Sep 1, 2008
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Expert Opinion on Pharmacotherapy
Expert Opinion on Pharmacotherapy
Expert Opinion on Drug Metabolism & Toxicology
Expert Review of Clinical Pharmacology
American Journal of Hypertension
The aim of the present study was to evaluate clinical correlates of silent cerebral white matter ... more The aim of the present study was to evaluate clinical correlates of silent cerebral white matter lesions (WML) in asymptomatic middle-aged untreated essential hypertensive patients. Fifty four mild to moderate never treated essential hypertensive patients (34 men, 20 women), aged 50-60 years (mean age 54 Ϯ4), without clinical evidence of target organ damage were studied. All patients underwent brainmagnetic resonance imaging, 24-h ambulatory blood pressure monitoring, echocardiography, and blood and urine analyses. Twenty-two (40%) hypertensives were found to have WML. Patients with WML have significantly higher values of both office and 24-hour systolic blood pressure (SBP) and pulse pressure (PP), whereas diastolic blood pressure (DBP) were not significantly different between groups. Furthermore, hypertensives with WML exhibited significantly lower values of glomerular filtrate rate, measured as creatinine clearance (CC), and a significantly higher left ventricular mass index (LVMI). These results suggest that SBP, and PP may be associated with the development of cerebral WML. The presence of WML in asymptomatic middle-aged hypertensives patients is associated with the existence of target organ damage at other levels, such as renal and cardiac impairment.
Giornale italiano di cardiologia (2006), 2016
The SPRINT study tested the hypothesis that hypertensive patients randomized to a more intensive ... more The SPRINT study tested the hypothesis that hypertensive patients randomized to a more intensive treatment, aimed at lowering systolic blood pressure (BP) below 120 mmHg have a lower incidence of major cardiovascular events when compared to patients randomized to a less intensive treatment (systolic BP reduction below 140 mmHg). Overall, 9361 patients were randomized to the more intensive (n=4678) or less intensive (n=4683) antihypertensive treatment. The study was prematurely interrupted because of an excess benefit in the more intensive arm. Indeed, the group randomized to the more intensive arm showed, when compared to the group randomized to the less intensive arm, a 25% reduction in the primary endpoint (1.65 vs 2.19% per year; p<0.001), a 43% reduction in cardiovascular death (0.25 vs 0.43%; p=0.005), a 27% reduction in all-cause death (1.03% vs 1.40%; p=0.003) and a 38% reduction in hospitalizations for heart failure (0.41 vs 0.67%; p<0.002). Unexpectedly, there was no ...
Journal of the American Heart Association, Jan 24, 2017
The different geometric patterns of the left ventricle may or may not coexist with chamber dilata... more The different geometric patterns of the left ventricle may or may not coexist with chamber dilatation. The prognostic impact of such a combination is unclear. We studied a cohort of 2635 initially untreated patients with hypertension, mean age 50 years. At entry, 24-hour ambulatory blood pressure progressively increased across the patterns of normal geometry, concentric left ventricular (LV) remodeling, eccentric nondilated LV hypertrophy (LVH), eccentric dilated LVH, concentric nondilated LVH, and concentric dilated LVH. During a mean follow-up of 9.7 years, 360 patients developed a first major cardiovascular event at a rate (×100 patient-years) of 1.41. The event rate was 0.93 in the group with normal LV geometry, 1.10 in the group with LV concentric remodeling, 1.40 in the group with nondilated eccentric LVH, 2.10 in the group with eccentric dilated LVH, 2.34 in the group with nondilated concentric LVH, and 4.67 in the group with dilated concentric LVH (log-rank test: P<0.001)...
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, Feb 17, 2017
We tested the hypothesis that left ventricular hypertrophy (LVH) interferes with the antithrombot... more We tested the hypothesis that left ventricular hypertrophy (LVH) interferes with the antithrombotic effects of dabigatran and warfarin in patients with atrial fibrillation (AF). This is a post-hoc analysis of the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) Study. We defined LVH by electrocardiography (ECG) and included patients with AF on the ECG tracing at entry. Hazard ratios (HR) for each dabigatran dose vs. warfarin were calculated in relation to LVH. LVH was present in 2353 (22.7%) out of 10 372 patients. In patients without LVH, the rates of primary outcome were 1.59%/year with warfarin, 1.60% with dabigatran 110 mg (HR vs. warfarin 1.01, 95% confidence interval (CI) 0.75-1.36) and 1.08% with dabigatran 150 mg (HR vs. warfarin 0.68, 95% CI 0.49-0.95). In patients with LVH, the rates of primary outcome were 3.21%/year with warfarin, 1.69% with dabigatran 110 mg (HR vs. warfarin 0.52, 95% CI 0.32-0.84) and 1.55% with 150 mg (HR vs. warfarin 0.48, 95% CI 0....
Circulation Research, 2017
Data in brief, 2016
We compared the follow-up data on loop diuretic use and renal function, as assessed by serum crea... more We compared the follow-up data on loop diuretic use and renal function, as assessed by serum creatinine levels, and the estimated glomerular filtration rate (eGFR), of two groups of consecutive ambulatory HF patients: 1) the clinically-guided group, in which management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department of Pisa (standard of care) and 2) the echo and B-type natriuretic peptide (BNP) guided group (patients conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group: Pisa, Perugia, Pavia; Verona, Auckland, and Veruno), in which therapy was delivered according to the serial assessment of BNP and echocardiography. Patients whose follow-up was based on standard of care had a significant higher prevalence of worsening renal function, that was likely related to higher diuretic dosages, whilst, a better management of renal function was observed in the echo-BNP-guided group. The data i...
Hypertension, 2016
Several randomized trials compared a more versus less intensive blood pressure–lowering strategy ... more Several randomized trials compared a more versus less intensive blood pressure–lowering strategy on the risk of major cardiovascular events and death. Cumulative meta-analyses and trial sequential analyses can establish whether and when firm evidence favoring a specific intervention has been reached from accrued literature. Therefore, we conducted a cumulative trial sequential analysis of 18 trials that randomly allocated 53 405 patients to a more or less intensive blood pressure–lowering strategy. We sought to ascertain the extent to which trial evidence added to previously accrued data. Outcome measures were stroke, myocardial infarction, heart failure, cardiovascular death, and all-cause death. Achieved blood pressure was 7.6/4.5 mm Hg lower with the more intensive than the less intensive blood pressure–lowering strategy. For stroke and myocardial infarction, the cumulative Z curve crossed the efficacy monitoring boundary solely after the SPRINT (Systolic Blood Pressure Intervent...
International journal of cardiology, Jan 18, 2016
B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide man... more B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide management of patients with chronic heart failure (HF).Thus, the aim of this retrospective, multicenter study was to compare outcomes and renal function in outpatients with chronic HF with reduced ejection fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven protocol for follow-up. In 1137 consecutive outpatients, management was guided according to echo-Doppler signs of elevated left ventricular filling pressure and BNP levels conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF=30%), while management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department in 567 (mean EF=33%). Propensity score, matching several confounding baseline variables, was used to match pairs based on treatment strategy. The median follow-up was 37.4months. After propensity matching,...
European journal of heart failure, Dec 20, 2016
A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse surviva... more A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). However, it is not known whether a reversible abnormal TAPSE at follow-up predicts survival. Our aim was to evaluate whether a reversible abnormal TAPSE is associated with a better survival in patients with chronic HFrEF. A complete echocardiography was performed in 706 patients with chronic HFrEF (LVEF ≤45%) at baseline and after 6 ± 3 months. Right ventricular (RV) systolic function was evaluated using TAPSE. The study endpoint was all-cause mortality. At baseline, TAPSE was severely reduced (≤14 mm) in 89 (13%) patients, and slightly reduced (>14 but <18 mm) in 157 (22%) patients. During a median follow-up of 40 months, 152 patients reached the endpoint. The event rate (per 100 patients/year) was lower in patients with persistently normal TAPSE (≥18 mm, n = 393) [3.3%, 95% confidence interval (CI) 2...
Circulation Research, 2016
Biochemistry and molecular biology international, 1994
We administered ethanol to pregnant rats and determined cholesterol, lipid phosphorus and fluores... more We administered ethanol to pregnant rats and determined cholesterol, lipid phosphorus and fluorescence anisotropy of diphenylhexatriene (DPH) and of trimethylaminophenyl hexatriene (TMA-DPH) in erythrocyte ghosts of newborn pups and of their mothers. Cholesterol content was different in dams and pups and changed after treatment. Age, but not ethanol, affected lipid phosphorus. Either age (dams versus pups) or treatment affected the curves of DPH fluorescence anisotropy (r) versus temperature (T), but those of TMA-DPH did not change, indicating that only the inner core of the membrane was influenced. We conclude that adult and erythrocyte ghosts differed for the lipid composition, for the dependence of r on T (for DPH) and for the effects of ethanol dosing on these parameters.
![Research paper thumbnail of [Antihypertensive therapy and cardiovascular prevention. The role of angiotensin II receptor blockers]](https://attachments.academia-assets.com/74131292/thumbnails/1.jpg)
](Giornale Italiano Di Cardiologia, Sep 1, 2007
Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart fail... more Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure, diabetic nephropathy, and other conditions. Over-stimulation of AT 2 receptor as a result of AT 1 blockade may contribute to the beneficial effects of ARBs through vasodilation and inhibition of cardiac and vascular hypertrophy and fibrosis. Some experimental studies, however, suggested that AT 2 receptor overstimulation, in addition to beneficial effects, might trigger inhibition of angiogenesis and apoptosis. In a review, some authors suggested that ARBs may increase the risk of myocardial infarction. This position triggered a hot scientific debate and further analyses of existing data. We completed a meta-analysis of randomized clinical trials comparing ARBs with either placebo or active drugs different from ARBs. ARBs were not associated with an excess risk of myocardial infarction (odds ratio 1.03 in a random-effect model and 1.02 in a fixed-effect model). Cardiovascular mortality did not differ between ARBs and drugs different from ARBs (odds ratio 1.00 in a random-effect model and 0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with placebo (odds ratio 0.91; 95% confidence interval 0.83-0.99; p = 0.042) in a prespecified subgroup analysis. Other meta-analyses confirmed these data. In conclusion, evidence from randomized trials does not support the hypothesis that AT 2 receptor over-stimulation produces harmful clinical effects. Current indications and contraindications to the use of ARBs in patients with hypertension, heart failure, and diabetic nephropathy should be maintained and probably extended to the entire class of these drugs.
Polskie Archiwum Medycyny Wewnetrznej-polish Archives of Internal Medicine, Sep 1, 2008
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Expert Opinion on Pharmacotherapy
Expert Opinion on Pharmacotherapy
Expert Opinion on Drug Metabolism & Toxicology
Expert Review of Clinical Pharmacology
American Journal of Hypertension
The aim of the present study was to evaluate clinical correlates of silent cerebral white matter ... more The aim of the present study was to evaluate clinical correlates of silent cerebral white matter lesions (WML) in asymptomatic middle-aged untreated essential hypertensive patients. Fifty four mild to moderate never treated essential hypertensive patients (34 men, 20 women), aged 50-60 years (mean age 54 Ϯ4), without clinical evidence of target organ damage were studied. All patients underwent brainmagnetic resonance imaging, 24-h ambulatory blood pressure monitoring, echocardiography, and blood and urine analyses. Twenty-two (40%) hypertensives were found to have WML. Patients with WML have significantly higher values of both office and 24-hour systolic blood pressure (SBP) and pulse pressure (PP), whereas diastolic blood pressure (DBP) were not significantly different between groups. Furthermore, hypertensives with WML exhibited significantly lower values of glomerular filtrate rate, measured as creatinine clearance (CC), and a significantly higher left ventricular mass index (LVMI). These results suggest that SBP, and PP may be associated with the development of cerebral WML. The presence of WML in asymptomatic middle-aged hypertensives patients is associated with the existence of target organ damage at other levels, such as renal and cardiac impairment.
Giornale italiano di cardiologia (2006), 2016
The SPRINT study tested the hypothesis that hypertensive patients randomized to a more intensive ... more The SPRINT study tested the hypothesis that hypertensive patients randomized to a more intensive treatment, aimed at lowering systolic blood pressure (BP) below 120 mmHg have a lower incidence of major cardiovascular events when compared to patients randomized to a less intensive treatment (systolic BP reduction below 140 mmHg). Overall, 9361 patients were randomized to the more intensive (n=4678) or less intensive (n=4683) antihypertensive treatment. The study was prematurely interrupted because of an excess benefit in the more intensive arm. Indeed, the group randomized to the more intensive arm showed, when compared to the group randomized to the less intensive arm, a 25% reduction in the primary endpoint (1.65 vs 2.19% per year; p<0.001), a 43% reduction in cardiovascular death (0.25 vs 0.43%; p=0.005), a 27% reduction in all-cause death (1.03% vs 1.40%; p=0.003) and a 38% reduction in hospitalizations for heart failure (0.41 vs 0.67%; p<0.002). Unexpectedly, there was no ...
Journal of the American Heart Association, Jan 24, 2017
The different geometric patterns of the left ventricle may or may not coexist with chamber dilata... more The different geometric patterns of the left ventricle may or may not coexist with chamber dilatation. The prognostic impact of such a combination is unclear. We studied a cohort of 2635 initially untreated patients with hypertension, mean age 50 years. At entry, 24-hour ambulatory blood pressure progressively increased across the patterns of normal geometry, concentric left ventricular (LV) remodeling, eccentric nondilated LV hypertrophy (LVH), eccentric dilated LVH, concentric nondilated LVH, and concentric dilated LVH. During a mean follow-up of 9.7 years, 360 patients developed a first major cardiovascular event at a rate (×100 patient-years) of 1.41. The event rate was 0.93 in the group with normal LV geometry, 1.10 in the group with LV concentric remodeling, 1.40 in the group with nondilated eccentric LVH, 2.10 in the group with eccentric dilated LVH, 2.34 in the group with nondilated concentric LVH, and 4.67 in the group with dilated concentric LVH (log-rank test: P<0.001)...
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, Feb 17, 2017
We tested the hypothesis that left ventricular hypertrophy (LVH) interferes with the antithrombot... more We tested the hypothesis that left ventricular hypertrophy (LVH) interferes with the antithrombotic effects of dabigatran and warfarin in patients with atrial fibrillation (AF). This is a post-hoc analysis of the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) Study. We defined LVH by electrocardiography (ECG) and included patients with AF on the ECG tracing at entry. Hazard ratios (HR) for each dabigatran dose vs. warfarin were calculated in relation to LVH. LVH was present in 2353 (22.7%) out of 10 372 patients. In patients without LVH, the rates of primary outcome were 1.59%/year with warfarin, 1.60% with dabigatran 110 mg (HR vs. warfarin 1.01, 95% confidence interval (CI) 0.75-1.36) and 1.08% with dabigatran 150 mg (HR vs. warfarin 0.68, 95% CI 0.49-0.95). In patients with LVH, the rates of primary outcome were 3.21%/year with warfarin, 1.69% with dabigatran 110 mg (HR vs. warfarin 0.52, 95% CI 0.32-0.84) and 1.55% with 150 mg (HR vs. warfarin 0.48, 95% CI 0....
Circulation Research, 2017
Data in brief, 2016
We compared the follow-up data on loop diuretic use and renal function, as assessed by serum crea... more We compared the follow-up data on loop diuretic use and renal function, as assessed by serum creatinine levels, and the estimated glomerular filtration rate (eGFR), of two groups of consecutive ambulatory HF patients: 1) the clinically-guided group, in which management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department of Pisa (standard of care) and 2) the echo and B-type natriuretic peptide (BNP) guided group (patients conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group: Pisa, Perugia, Pavia; Verona, Auckland, and Veruno), in which therapy was delivered according to the serial assessment of BNP and echocardiography. Patients whose follow-up was based on standard of care had a significant higher prevalence of worsening renal function, that was likely related to higher diuretic dosages, whilst, a better management of renal function was observed in the echo-BNP-guided group. The data i...
Hypertension, 2016
Several randomized trials compared a more versus less intensive blood pressure–lowering strategy ... more Several randomized trials compared a more versus less intensive blood pressure–lowering strategy on the risk of major cardiovascular events and death. Cumulative meta-analyses and trial sequential analyses can establish whether and when firm evidence favoring a specific intervention has been reached from accrued literature. Therefore, we conducted a cumulative trial sequential analysis of 18 trials that randomly allocated 53 405 patients to a more or less intensive blood pressure–lowering strategy. We sought to ascertain the extent to which trial evidence added to previously accrued data. Outcome measures were stroke, myocardial infarction, heart failure, cardiovascular death, and all-cause death. Achieved blood pressure was 7.6/4.5 mm Hg lower with the more intensive than the less intensive blood pressure–lowering strategy. For stroke and myocardial infarction, the cumulative Z curve crossed the efficacy monitoring boundary solely after the SPRINT (Systolic Blood Pressure Intervent...
International journal of cardiology, Jan 18, 2016
B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide man... more B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide management of patients with chronic heart failure (HF).Thus, the aim of this retrospective, multicenter study was to compare outcomes and renal function in outpatients with chronic HF with reduced ejection fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven protocol for follow-up. In 1137 consecutive outpatients, management was guided according to echo-Doppler signs of elevated left ventricular filling pressure and BNP levels conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF=30%), while management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department in 567 (mean EF=33%). Propensity score, matching several confounding baseline variables, was used to match pairs based on treatment strategy. The median follow-up was 37.4months. After propensity matching,...
European journal of heart failure, Dec 20, 2016
A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse surviva... more A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). However, it is not known whether a reversible abnormal TAPSE at follow-up predicts survival. Our aim was to evaluate whether a reversible abnormal TAPSE is associated with a better survival in patients with chronic HFrEF. A complete echocardiography was performed in 706 patients with chronic HFrEF (LVEF ≤45%) at baseline and after 6 ± 3 months. Right ventricular (RV) systolic function was evaluated using TAPSE. The study endpoint was all-cause mortality. At baseline, TAPSE was severely reduced (≤14 mm) in 89 (13%) patients, and slightly reduced (>14 but <18 mm) in 157 (22%) patients. During a median follow-up of 40 months, 152 patients reached the endpoint. The event rate (per 100 patients/year) was lower in patients with persistently normal TAPSE (≥18 mm, n = 393) [3.3%, 95% confidence interval (CI) 2...
Circulation Research, 2016
Biochemistry and molecular biology international, 1994
We administered ethanol to pregnant rats and determined cholesterol, lipid phosphorus and fluores... more We administered ethanol to pregnant rats and determined cholesterol, lipid phosphorus and fluorescence anisotropy of diphenylhexatriene (DPH) and of trimethylaminophenyl hexatriene (TMA-DPH) in erythrocyte ghosts of newborn pups and of their mothers. Cholesterol content was different in dams and pups and changed after treatment. Age, but not ethanol, affected lipid phosphorus. Either age (dams versus pups) or treatment affected the curves of DPH fluorescence anisotropy (r) versus temperature (T), but those of TMA-DPH did not change, indicating that only the inner core of the membrane was influenced. We conclude that adult and erythrocyte ghosts differed for the lipid composition, for the dependence of r on T (for DPH) and for the effects of ethanol dosing on these parameters.
Giornale Italiano Di Cardiologia, Sep 1, 2007
Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart fail... more Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure, diabetic nephropathy, and other conditions. Over-stimulation of AT 2 receptor as a result of AT 1 blockade may contribute to the beneficial effects of ARBs through vasodilation and inhibition of cardiac and vascular hypertrophy and fibrosis. Some experimental studies, however, suggested that AT 2 receptor overstimulation, in addition to beneficial effects, might trigger inhibition of angiogenesis and apoptosis. In a review, some authors suggested that ARBs may increase the risk of myocardial infarction. This position triggered a hot scientific debate and further analyses of existing data. We completed a meta-analysis of randomized clinical trials comparing ARBs with either placebo or active drugs different from ARBs. ARBs were not associated with an excess risk of myocardial infarction (odds ratio 1.03 in a random-effect model and 1.02 in a fixed-effect model). Cardiovascular mortality did not differ between ARBs and drugs different from ARBs (odds ratio 1.00 in a random-effect model and 0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with placebo (odds ratio 0.91; 95% confidence interval 0.83-0.99; p = 0.042) in a prespecified subgroup analysis. Other meta-analyses confirmed these data. In conclusion, evidence from randomized trials does not support the hypothesis that AT 2 receptor over-stimulation produces harmful clinical effects. Current indications and contraindications to the use of ARBs in patients with hypertension, heart failure, and diabetic nephropathy should be maintained and probably extended to the entire class of these drugs.