Publications by authors named "Paolo Verdecchia"

287 Publications

Aprocitentan, A Dual Endothelin Receptor Antagonist Under Development for the Treatment of Resistant Hypertension.

Cardiol Ther 2021 Jul 12. Epub 2021 Jul 12.

Department of Medicine and Centro di Ricerca Clinica e Traslazionale (CERICLET), University of Perugia, Perugia, Italy.

Aprocitentan (ACT-132577) is an orally active, dual endothelin-1 (ET-1) receptor antagonist that prevents the binding of ET-1 to both ETA/ETB receptors. It is an active metabolite of macitentan (obtained by oxidative depropylation), an orphan drug used for the treatment of pulmonary arterial hypertension. Aprocitentan is highly bound to plasma proteins and is eliminated in both urine and feces. It is well tolerated across all doses (up to 600 mg with single dose and 100 mg once a day at multiple doses). Its pharmacokinetic profile shows a half-life of 44 h, fitting a once-daily dosing regimen with plasma ET-1 concentrations (reflecting ET receptor antagonism), significantly increasing with doses ≥ 25 mg. Only minor differences in exposure between healthy females and males, healthy elderly and adult subjects, fed and fasted conditions, and renal function have been observed. Aprocitentan in patients with resistant hypertension is currently under investigation in the PRECISION phase III trial (ClinicalTrials identifier: NCT03541174). Nonetheless, results of pre-clinical data and studies in humans support the potential role of aprocitentan in this clinical setting. The absolute blood pressure (BP) reductions with aprocitentan are in the ranges established as a surrogate for reduction in cardiovascular morbidity in hypertension. Significant changes in BP with aprocitentan are observed within 14 days, and its BP-lowering effects have also been documented with ambulatory BP monitoring. Finally, aprocitentan enhances the BP-lowering effects of other antihypertensive drugs, including renin-angiotensin-system blockers. In conclusion, aprocitentan ameliorates the effects of ET-1 and could potentially reduce BP and provide broader cardiovascular protection in patients with resistant hypertension. Available data support the hypothesis that this new agent could expand our antihypertensive arsenal in resistant hypertension, making aprocitentan an attractive candidate for further large-scale trials.
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http://dx.doi.org/10.1007/s40119-021-00233-7DOI Listing
July 2021

SARS-CoV-2 infection and ACE2 inhibition.

J Hypertens 2021 08;39(8):1555-1558

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.

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http://dx.doi.org/10.1097/HJH.0000000000002859DOI Listing
August 2021

[Atrial fibrillation and sudden cardiac death: a mystery to unravel?]

G Ital Cardiol (Rome) 2021 Jul;22(7):544-553

Fondazione Umbra Cuore e Ipertensione-ONLUS e S.C. Cardiologia, Ospedale S. Maria della Misericordia, Perugia.

Atrial fibrillation has been associated with stroke, heart failure and cardiovascular mortality. Although several studies have recently put forward a connection between atrial fibrillation and sudden cardiac death, whether the arrhythmia should be regarded as an independent predictor of potentially harmful ventricular tachycardias is not utterly clear. Nor have the underlying mechanisms been thoroughly investigated yet. A cause-effect relationship seems to be involved in some cases. In other clinical scenarios, however, atrial fibrillation could be a mere expression of the severity of the underlying structural or electrical heart disease, therefore playing an unremarkable pathophysiologic role in this setting. Moreover, despite some exceptions, current guidelines do not provide a straightforward approach to identify which patients with atrial fibrillation bear a greater risk of sudden cardiac death. The aim of this review is to discuss the available clinical evidence in this field, suggesting a pathophysiologic sequence and a patient-tailored approach for an effective risk stratification and management of patients with atrial fibrillation.
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http://dx.doi.org/10.1714/3629.36105DOI Listing
July 2021

Blood pressure increase after Pfizer/BioNTech SARS-CoV-2 vaccine.

Eur J Intern Med 2021 Jun 16. Epub 2021 Jun 16.

Department of Medicine and Surgery, University of Insubria, Varese, Italy; Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ejim.2021.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206586PMC
June 2021

Ageing, ACE2 deficiency and bad outcome in COVID-19.

Clin Chem Lab Med 2021 Jun 14. Epub 2021 Jun 14.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.

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http://dx.doi.org/10.1515/cclm-2021-0658DOI Listing
June 2021

An update on antithrombotic therapy in atrial fibrillation patients in long-term ambulatory setting after percutaneous coronary intervention: where do we go from here?

Expert Opin Pharmacother 2021 Jul 7:1-19. Epub 2021 Jul 7.

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Introduction: In the treatment of patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI), it is unclear which combination of antithrombotic drugs is preferable and which is the optimal duration of treatment.

Areas Covered: The authors review the available evidence in this area resulting from single studies and meta-analyses. In the absence of direct head-to-head comparisons between different non-vitamin K oral anticoagulants (NOAC), the authors review the available studies with NOACS in these patients and derived indirect comparisons.

Expert Opinion: In patients with AF who undergo PCI, a dual antithrombotic strategy which includes a NOAC plus single antiplatelet therapy with a P2Y12 inhibitor (preferably clopidogrel) should be considered as the preferred treatment option in most cases. Oral anticoagulation associated with dual antiplatelet therapy (triple antithrombotic therapy) should be offered for no longer than 30 days to patients with very high thrombotic and low hemorrhagic risk. It is unclear whether the dual antithrombotic strategy should be continued beyond 12 months in patients at high risk of thrombotic events. Additional data from adequately powered controlled studies are needed to support the long-term efficacy of this strategy and to establish the best patient-tailored approach in this complex scenario.
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http://dx.doi.org/10.1080/14656566.2021.1937119DOI Listing
July 2021

The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) Study.

Panminerva Med 2021 May 14. Epub 2021 May 14.

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Background: the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study is a prospective registry of morbidity and mortality in initially untreated patients with essential hypertension whose initial diagnostic evaluation included 24-hour ambulatory blood pressure monitoring according to a standardized protocol. The present article summarizes the main results of the PIUMA study.

Methods: the PIUMA study is conducted in three Hospitals in Umbria, Central Italy. After their initial assessment at entry, patients are followed in the outpatient clinic of the referring hospital and in collaboration with their family doctors. Telephone interviews with patients and meetings with family doctors are periodically conducted to ascertain the incidence of major complications of hypertension.

Results: the PIUMA study gave us a tremendous opportunity to investigate several aspects related to hypertension: (1) Cross sectional studies focused on the association between clinic and 24-hour ABP and organ damage; (2) Longitudinal studies focused on the association between 24-hour ABP and hypertensive organ damage at cardiac level and other levels with the subsequent incidence of major cardiovascular events and mortality; (3) Longitudinal studies exploring the prognostic impact of other risk factors in hypertensive patients (i.e., diabetes, dyslipidemia, atrial fibrillation, left ventricular dysfunction, etc). The PIUMA study provided the first ever evidence of the prognostic value of (a) 24-hour ambulatory blood pressure monitoring; (b) regression of echocardiographic left ventricular hypertrophy in hypertensive patients.

Conclusions: the PIUMA registry gave us an enormous opportunity for investigating several pathophysiologic, diagnostic and therapeutic aspects related to management of hypertensive patients. Some of our studies have been mentioned in several Hypertension Guidelines to support some specific statements.
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http://dx.doi.org/10.23736/S0031-0808.21.04383-4DOI Listing
May 2021

SARS-CoV-2 vaccines: Lights and shadows.

Eur J Intern Med 2021 06 30;88:1-8. Epub 2021 Apr 30.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.

Vaccines to prevent acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicit an immune neutralizing response. Some concerns have been raised regarding the safety of SARS-CoV-2 vaccines, largely based on case-reports of serious thromboembolic events after vaccination. Some mechanisms have been suggested which might explain the adverse cardiovascular reactions to SARS-CoV-2 vaccines. Different vaccine platforms are currently available which include live attenuated vaccines, inactivated vaccines, recombinant protein vaccines, vector vaccines, DNA vaccines and RNA vaccines. Vaccines increase the endogenous synthesis of SARS-CoV-2 Spike proteins from a variety of cells. Once synthetized, the Spike proteins assembled in the cytoplasma migrate to the cell surface and protrude with a native-like conformation. These proteins are recognized by the immune system which rapidly develops an immune response. Such response appears to be quite vigorous in the presence of DNA vaccines which encode viral vectors, as well as in subjects who are immunized because of previous exposure to SARS-CoV-2. The resulting pathological features may resemble those of active coronavirus disease. The free-floating Spike proteins synthetized by cells targeted by vaccine and destroyed by the immune response circulate in the blood and systematically interact with angiotensin converting enzyme 2 (ACE2) receptors expressed by a variety of cells including platelets, thereby promoting ACE2 internalization and degradation. These reactions may ultimately lead to platelet aggregation, thrombosis and inflammation mediated by several mechanisms including platelet ACE2 receptors. Whereas Phase III vaccine trials generally excluded participants with previous immunization, vaccination of huge populations in the real life will inevitably include individuals with preexisting immunity. This might lead to excessively enhanced inflammatory and thrombotic reactions in occasional subjects. Further research is urgently needed in this area.
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http://dx.doi.org/10.1016/j.ejim.2021.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084611PMC
June 2021

Joint effect of heart failure and coronary artery disease on the risk of death during hospitalization for COVID-19.

Eur J Intern Med 2021 07 19;89:81-86. Epub 2021 Apr 19.

Istituti Clinici Scientifici Maugeri IRCCS, Italy.

Aims: heart failure (HF) and coronary artery disease (CAD) are independent predictors of death in patients with COVID-19. The adverse prognostic impact of the combination of HF and CAD in these patients is unclear.

Methods And Results: we analysed data from 954 consecutive patients hospitalized for SARS-CoV-2 in five Italian Hospitals from February 23 to May 22, 2020. The study was a systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the outcome measure. Mean duration of hospitalization was 33 days. Mortality was 11% in the total population and 7.4% in the group without evidence of HF or CAD (reference group). Mortality was 11.6% in the group with CAD and without HF (odds ratio [OR]: 1.6, p = 0.120), 15.5% in the group with HF and without CAD (OR: 2.3, p = 0.032), and 35.6% in the group with CAD and HF (OR: 6.9, p<0.0001). The risk of mortality in patients with CAD and HF combined was consistently higher than the sum of risks related to either disorder, resulting in a significant synergistic effect (p<0.0001) of the two conditions. Age-adjusted attributable proportion due to interaction was 64%. Adjusting for the simultaneous effects of age, hypotension, and lymphocyte count did not significantly lower attributable proportion which persisted statistically significant (p = 0.0360).

Conclusion: The combination of HF and CAD exerts a marked detrimental impact on the risk of mortality in hospitalized patients with COVID-19, which is independent on other adverse prognostic markers.
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http://dx.doi.org/10.1016/j.ejim.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055166PMC
July 2021

Chronological age and vascular age staring at each other on the ring of cardiovascular prevention.

Int J Cardiol Hypertens 2021 Mar 6;8:100076. Epub 2021 Jan 6.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Department of Cardiology, Hospital S. Maria Della Misericordia, Perugia, Italy.

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http://dx.doi.org/10.1016/j.ijchy.2021.100076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006060PMC
March 2021

[Progress in the treatment of hypertension].

G Ital Cardiol (Rome) 2021 Apr;22(4):253-266

Dipartmento di Medicina e Chirurgia, Università degli Studi dell'Insubria, Varese - Dipartimento di Medicina e Riabilitazione Cardiopolmonare, Istituti Clinici Scientifici Maugeri, IRCCS Tradate (VA).

Over the past five decades, we have witnessed significant developments in the management of patients with arterial hypertension and elucidation of basic mechanisms involved in the disease. Many of these progresses resulted from experimental and clinical studies conducted in Italy. Several randomized clinical trials have been carried out worldwide and in Italy according to the best available evidence-based medicine rules, often before the initiation of comparable studies in different cardiovascular areas (acute coronary syndromes, arrhythmias, heart failure). Because of these progresses, we currently dispose of a huge therapeutic armamentarium of effective and generally well tolerated antihypertensive drugs. Ablation of renal nerves is a procedure which is re-gaining attention. We are also learning how to correctly measure blood pressure not only in the hospital setting, but also during normal daily activities using 24 h ambulatory blood pressure monitoring and self-measured home blood pressure. Out-of-office blood pressure proved to be superior to office blood pressure in its relationship with hypertensive organ damage and risk of major cardiovascular complications and mortality. Currently, we should improve our understanding of out-of-office blood pressure measurements and the clinical use of several available drug combinations according to their efficacy and tolerability in the single patients. We should also learn more about optimal blood pressure targets to be achieved in the general hypertensive population is specific subgroups at different cardiovascular risk.
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http://dx.doi.org/10.1714/3574.35569DOI Listing
April 2021

Intensive cardiac care unit admission trends during the COVID-19 outbreak in Italy: a multi-center study.

Intern Emerg Med 2021 Mar 25. Epub 2021 Mar 25.

Cardiology Department, Santa Maria Della Misericordia Hospital, Perugia, Italy.

A significant decline in the admission to intensive cardiac care unit (ICCU) has been noted in Italy during the COVID-19 outbreak. Previous studies have provided data on clinical features and outcome of these patients, but information is still incomplete. In this multicenter study conducted in six ICCUs, we enrolled consecutive adult patients admitted to ICCU in three specific time intervals: from February 8 to March 9, 2020 [before national lockdown (pre-LD)], from March 10 to April 9, 2020 [during the first period of national lockdown (in-LD)] and from May 18 to June 17, 2020 [soon after the end of all containment measures (after-LD)]. Compared to pre-LD, in-LD was associated with a significant drop in the admission to ICCU for all causes (- 35%) and acute coronary syndrome (ACS; - 49%), with a rebound soon after-LD. The in-LD reduction was greater for women (- 49%) and NSTEMI (- 61%) compared to men (- 28%) and STEMI (- 33%). Length-of-stay, and in-hospital mortality did not show any significant change from to pre-LD to in-LD in the whole population as well as in the ACS group. This study confirms a notable reduction in the admissions to ICCUs from pre-LD to in-LD followed by an increment in the admission rates after-LD. These data strongly suggest that people, particularly women and patients with NSTEMI, are reluctant to seek medical care during lockdown, possibly due to the fear of viral infection. Such a phenomenon, however, was not associated with a rise in mortality among patients who get hospitalization.
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http://dx.doi.org/10.1007/s11739-021-02718-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993896PMC
March 2021

Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project.

J Nephrol 2021 Mar 23. Epub 2021 Mar 23.

Department of Medicine, University of Padua, Padua, Italy.

Background: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database.

Methods: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol.

Results: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m2with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides.

Conclusions: The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria.
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http://dx.doi.org/10.1007/s40620-021-00985-4DOI Listing
March 2021

The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk.

Clin Res Cardiol 2021 Jul 18;110(7):1073-1082. Epub 2021 Feb 18.

Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, IRCCS S. Luca Hospital, Lucca, Italy.

Introduction: Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis.

Aim: We assessed the prognostic role of SUA in patients with and without MS.

Methods: We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure.

Results: A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p < 0.0001) and provided a significant net reclassification improvement of 7.1% over the diagnosis of MS for CVM (p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15-2.79]; p < 0.0001) after the adjustment for MS, its single components and renal function. Three specific combinations of the MS components were associated with higher CVM when increasing SUA levels were reported, and systemic hypertension was the only individual component ever-present (all p < 0.0001).

Conclusion: Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification.
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http://dx.doi.org/10.1007/s00392-021-01815-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238697PMC
July 2021

High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid.

Eur J Prev Cardiol 2021 Feb 14. Epub 2021 Feb 14.

Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.

Aims : Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR).

Methods And Results : Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P < 0.0001) over a multivariable model. However, the risk of CVM related to high UA (≥5.5 mg/dL, top tertile) was much lower in the subjects with HR
Conclusion : This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.
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http://dx.doi.org/10.1093/eurjpc/zwab023DOI Listing
February 2021

The Link between Inflammation and Hypertension: Unmasking Mediators.

Am J Hypertens 2021 Feb 11. Epub 2021 Feb 11.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia - Italy.

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http://dx.doi.org/10.1093/ajh/hpab034DOI Listing
February 2021

Masked Nocturnal Hypertension: A Complex Phenomenon to Detect in Clinical Practice.

Am J Hypertens 2021 06;34(6):578-580

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.

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http://dx.doi.org/10.1093/ajh/hpab007DOI Listing
June 2021

Impact of type II diabetes and gender on major clinical events after percutaneous coronary intervention.

Prim Care Diabetes 2021 04 2;15(2):347-351. Epub 2020 Dec 2.

Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Aims: Incidence of type 2 diabetes is markedly rising worldwide. Some studies suggest that the occurrence of major adverse cardiac events (MACE) after PCI is different in men and women, but data are conflicting.

Methods: We studied patients with stable coronary artery disease (CAD) who underwent PCI between years 2000 and 2017. Patients with primary PCI were excluded. Drug-eluting stent (DES) and dual antiplatelet therapy were administered in all patients. We followed these patients for a mean of 68 months. MACE as a composite of coronary revascularization, myocardial infarction or cardiovascular death was sought in three time windows.

Results: We studied 1799 patients, 29.6% of whom with diabetes. Women were 52%. In multivariate analyses, there were no significant differences in the risk of MACE between diabetic and non-diabetic patients, as well as between men and women, neither in different time windows, nor in the whole duration of follow-up. The components of MACE did not show any significant differences between diabetic and non-diabetic patients, as well as between the genders.

Conclusion: In our patients with stable CAD who received a modern therapeutic management after PCI, neither type 2 diabetes nor gender were associated with an excess risk of MACE.
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http://dx.doi.org/10.1016/j.pcd.2020.11.004DOI Listing
April 2021

Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.

J Hypertens 2021 Feb;39(2):333-340

Medicina Interna I, Ca' Foncello University Hospital, Treviso.

Objective: Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events.

Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes.

Results: Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group.

Conclusion: Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.
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http://dx.doi.org/10.1097/HJH.0000000000002600DOI Listing
February 2021

Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation.

Eur Heart J 2021 05;42(20):2019

Department of Cardiology, Hospital 'S. Maria della Misericordia', Perugia, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehaa906DOI Listing
May 2021

RAAS Inhibitors and Risk of Covid-19.

N Engl J Med 2020 Nov 27;383(20):1990-1991. Epub 2020 Oct 27.

University of Perugia, Perugia, Italy.

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http://dx.doi.org/10.1056/NEJMc2030446DOI Listing
November 2020

The 2020 International Society of Hypertension global hypertension practice guidelines - key messages and clinical considerations.

Eur J Intern Med 2020 12 22;82:1-6. Epub 2020 Sep 22.

Department of Medicine and Surgery, University of Insubria, Varese and Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, Varese, Italy.

The International Society of Hypertension (ISH) has recently developed practice guidelines for the management of hypertension in adults aged ≥18 years. Conceptually, the 2020 ISH Guidelines are closer to the 2018 ESC/ESH Guidelines rather than to the 2017 ACC/AHA Guidelines. The ISH Guidelines have two distinctive features when compared with the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines. First, they are written in a concise and easy-to-read style; second, they focuses on practical issues related to the management of hypertension in 'high-income' as well as in 'low-income' countries, where there is limited access to resources for the diagnosis and treatment of hypertension. In our opinion, the 2020 ISH Guidelines share with the 2018 ESC/ESH Guidelines an important limitation which may impair the retention of these key aspects of Guidelines by physicians, with consequent difficult adoption in clinical practice. It consists in the definition of several blood pressure targets in relation to age, target organ damage and concomitant disease. We believe that results of randomized clinical trials and meta-analysis do not support the recommendation of differential BP targets, as well as of rigid 'safety boundaries'. This review critically examines similarities and differences across the three major Hypertension Guidelines, which include the definition of hypertension, drug treatment, and blood pressure targets, with emphasis on key messages relevant for clinical practice.
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http://dx.doi.org/10.1016/j.ejim.2020.09.001DOI Listing
December 2020

Fragmented QRS as an early predictor of left ventricular systolic dysfunction in healthy individuals: a nested case-control study in the era of speckle tracking echocardiography.

Cardiovasc Ultrasound 2020 Aug 13;18(1):33. Epub 2020 Aug 13.

Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Several studies addressed the association between fragmented QRS (fQRS) on 12-lead EKG and left ventricular (LV) dysfunction in patients with a variety of cardiovascular disorders. We tested such association in healthy individuals.

Methods: Out of 500 healthy participants without -overt cardiovascular disease from the Shiraz Heart Study cohort, we identified 20 subjects with fQRS (cases) and 20 peers without fQRS (controls). Global LV longitudinal strain (GLS) was measured by speckle tracking echocardiography in the two groups. Comparison was made between case and control groups by using chi-square or independent sample t-test or ANOVA.

Results: Age, gender, ejection fraction, LV volume and dimensions did not differ between the case and the control groups. Overall, 14 subjects out of 40 had reduced GLS (≤20%) and 10 of them (25%) had fQRS. GLS was significantly lower in the group with fQRS than in the control group (19.9 ± 1.8 vs 21.4 ± 1.6; p = 0.009).

Conclusions: Healthy subjects with fQRS present regional LV systolic dysfunction, assessed by GLS, in the presence of a normal ejection fraction. These data suggest that fQRS may be a promising tool to identify apparently healthy subjects with regional LV systolic dysfunction.
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http://dx.doi.org/10.1186/s12947-020-00216-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427061PMC
August 2020

Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.

J Hypertens 2021 Jan;39(1):62-69

Hospital S. Maria della Misericordia, Perugia, Italy.

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension.

Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders.

Results: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively.

Conclusion: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).
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http://dx.doi.org/10.1097/HJH.0000000000002589DOI Listing
January 2021

Electrocardiographic features of patients with COVID-19 pneumonia.

Eur J Intern Med 2020 08 20;78:101-106. Epub 2020 Jun 20.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia - Italy.

Background: . The electrocardiographic (ECG) changes which may occur during hospitalization for COVID-19 have not yet been comprehensively assessed.

Patients And Methods: . We examined 50 patients admitted to hospital with proven COVID-19 pneumonia. At entry, all patients underwent a detailed clinical examination, 12-lead ECG, laboratory tests and arterial blood gas test. ECG was also recorded at discharge and in case of worsening clinical conditions.

Results: . Mean age of patients was 64 years and 72% were men. At baseline, 30% of patients had ST-T abnormalities, and 33% had left ventricular hypertrophy. During hospitalization, 26% of patients developed new ECG abnormalities which included atrial fibrillation, ST-T changes, tachy-brady syndrome, and changes consistent with acute pericarditis. One patient was transferred to intensive care unit for massive pulmonary embolism with right bundle branch block, and another for non-ST segment elevation myocardial infarction. Patients free of ECG changes during hospitalization were more likely to be treated with antiretrovirals (68% vs 15%, p = 0.001) and hydroxychloroquine (89% vs 62%, p = 0.026) versus those who developed ECG abnormalities after admission. Most measurable ECG features at discharge did not show significant changes from baseline (all p>0.05) except for a slightly decrease in Cornell voltages (13±6 vs 11±5 mm; p = 0.0001) and a modest increase in the PR interval. The majority (54%) of patients with ECG abnormalities had 2 prior consecutive negative nasopharyngeal swabs. ECG abnormalities were first detected after an average of about 30 days from symptoms' onset (range 12-51 days).

Conclusions: . ECG abnormalities during hospitalization for COVID-19 pneumonia reflect a wide spectrum of cardiovascular complications, exhibit a late onset, do not progress in parallel with pulmonary abnormalities and may occur after negative nasopharyngeal swabs.
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http://dx.doi.org/10.1016/j.ejim.2020.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305928PMC
August 2020

Treatment strategies for isolated systolic hypertension in elderly patients.

Expert Opin Pharmacother 2020 Oct 25;21(14):1713-1723. Epub 2020 Jun 25.

Department of Medicine, University of Perugia , Perugia, Italy.

Introduction: Hypertension is a major and modifiable risk factor for cardiovascular disease. Its prevalence is rising as the result of population aging. Isolated systolic hypertension mostly occurs in older patients accounting for up to 80% of cases.

Areas Covered: The authors systematically review published studies to appraise the scientific and clinical evidence supporting the role of blood pressure control in elderly patients with isolated systolic hypertension, and to assess the influence of different drug treatment regimens on outcomes.

Expert Opinion: Antihypertensive treatment of isolated systolic hypertension significantly reduces the risk of morbidity and mortality in elderly patients. Thiazide diuretics and dihydropyridine calcium-channel blockers are the primary compounds used in randomized clinical trials. These drugs can be considered as first-line agents for the management of isolated systolic hypertension. Free or fixed combination therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and calcium-channel blockers or thiazide-like diuretics should also be considered, particularly when compelling indications such as coronary artery disease, chronic kidney disease, diabetes, and congestive heart failure coexist. There is also hot scientific debate on the optimal blood pressure target to be achieved in elderly patients with isolated systolic hypertension, but current recommendations are scarcely supported by evidence.
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http://dx.doi.org/10.1080/14656566.2020.1781092DOI Listing
October 2020

The revolution of the anti-diabetic drugs in cardiology.

Eur Heart J Suppl 2020 Jun 29;22(Suppl E):E162-E166. Epub 2020 Mar 29.

Dipartimento di Medicina, Università di Perugia, Perugia, Italy.

Beginning in December 2008, under the auspices of Food and Drug Administration, numerous controlled clinical trial were planned, and in part completed, concerning the cardiovascular (CV) effects of hypoglycaemic drug in patients with Type 2 diabetes mellitus. At least 9 studies have been concluded, 13 are still open, and 4 have been initiated and closed ahead of time. Of the nine completed studies, three concerned inhibitor of the dipeptidyl peptidase 4 (inhibitors of DPP-4), four the glucagon-like peptide 1 agonist (GLP-1 agonist), and two the inhibitor of sodium-glucose co-transporter-2 (inhibitors of SGLT-2). Only four studies demonstrated the superiority, and not the mere 'non-inferiority', of the anti-diabetic drugs compared to placebo, in addition to standard treatment, in terms of reduction of the primary endpoint (CV death, non-fatal myocardial infarction, and non-fatal stroke). Two of the four studies regarded GLP-1 analogues (liraglutide and semaglutide), and two inhibitors of SGLT-2 (empaglifozin and canaglifozin). As a whole, these studies provided solid data supporting major beneficial CV effects of anti-diabetic drugs. During the next 3-4 years, an equal number of studies will be completed and published, so we will soon have the 'final word' on this issue. In the meantime, the clinical cardiologist should become familiar with these drugs, selecting the patients able to gain the best clinical advantage from this treatment, also by establishing a close relationship with the diabetologist.
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http://dx.doi.org/10.1093/eurheartj/suaa084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270967PMC
June 2020

COVID-19: ACE2centric Infective Disease?

Hypertension 2020 08 1;76(2):294-299. Epub 2020 Jun 1.

Department of Medicine and Surgery, and Chronic Disease Research Center (MACRO), University of Insubria, Varese, Italy (A.S., F.A.).

Diffuse pulmonary inflammation, endothelial inflammation, and enhanced thrombosis are cardinal features of coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2. These features are reminiscent of several adverse reactions triggered by angiotensin II and opposed by angiotensin, in many experimental models. Severe acute respiratory syndrome coronavirus 2 binds to ACE2 (angiotensin-converting enzyme 2) receptors and entries into the cell through the fusion of its membrane with that of the cell. Hence, it downregulates these receptors. The loss of ACE2 receptor activity from the external site of the membrane will lead to less angiotensin II inactivation and less generation of antiotensin. In various experimental models of lung injury, the imbalance between angiotensin II overactivity and of antiotensin deficiency triggered inflammation, thrombosis, and other adverse reactions. In COVID-19, such imbalance could play an important role in influencing the clinical picture and outcome of the disease. According to this line of thinking, some therapeutic approaches including recombinant ACE2, exogenous angiotensin, and angiotensin receptor blockers seem particularly promising and are being actively tested.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15353DOI Listing
August 2020

Severity of COVID-19: The importance of being hypertensive.

Monaldi Arch Chest Dis 2020 May 20;90(2). Epub 2020 May 20.

Fondazione Umbra Cuore e Ipertensione ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia.

The novel respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused a cluster of pneumonia cases in China at the end of 2019. After few months, it led to a pandemic that has spread throughout most countries of the world (https://coronavirus.jhu.edu/map.html).
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http://dx.doi.org/10.4081/monaldi.2020.1372DOI Listing
May 2020
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