Maloberti Dott. Alessandro

Pubblicazioni su PubMed

• Role of PCSK9 Inhibitors in Venous Thromboembolism: Current Evidence and Unmet Clinical Needs.
  Eur Heart J Cardiovasc Pharmacother

  2024 Oct;():. doi: pvae076.
  
  Zuin Marco, Corsini Alberto, Dalla Valle Chiara, De Rosa Catia, Maloberti Alessandro, Mojoli Marco, Rizzo Massimiliano, Ciccirillo Francesco, Madrid Alfredo, Riccio Carmine, Grimaldi Massimo, Colivicchi Furio, Oliva Fabrizio, Temporelli Pier Luigi
  
  Abstract
  
  Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have recently emerged as promising therapeutic agents for lowering low-density lipoprotein cholesterol and reducing the risk of cardiovascular events. Moreover, preliminary evidence from randomized controlled trials (RCTs) suggests that PCSK9i may also offer beneficial effects for patients following venous thromboembolism (VTE), with the most significant reductions in risk appearing over time, particularly beyond the first year of treatment. However, there is a lack of randomized controlled data supporting their efficacy and safety in conjunction with standard anticoagulation therapy. This article aims to critically evaluate the existing evidence for the use of PCSK9i as a complementary therapy for VTE risk reduction, while also identifying unmet clinical and research needs and proposing potential strategies to address these knowledge gaps.
  
  © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
  
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• Secondary prevention and extreme cardiovascular risk evaluation (SEVERE-0): Prevalence of extreme cardiovascular risk in cardiological rehabilitation patients and its impact on functional improvement.
  Nutr Metab Cardiovasc Dis

  2024 Aug;():. doi: S0939-4753(24)00303-X.
  
  Tognola Chiara, Myriam Intravaia Rita Cristina, Senini Eleonora, Pezzoli Stefano, Riccio Alfonso, Gualini Elena, Fabbri Saverio, Bellantonio Valentina, Politi Francesco, Campana Marta, Fucile Ilaria, Mancusi Costantino, Golia Enrica, Cesaro Arturo, De Luca Nicola, Calabrò Paolo, Giannattasio Cristina, Maloberti Alessandro
  
  Abstract
  
  BACKGROUND AND AIMS:
  Patients with recent Acute Coronary Syndrome (ACS) or Chronic Coronary Syndrome (CCS) are all at very high CardioVascular (CV) risk. However, some of them are more likely to experience recurrent cardiovascular events (i.e extreme CV risk). A definition of which patients should be included in this category has been recently proposed by the European Society of Cardiology but data on its prevalence are still lacking, especially in the context of Cardiac Rehabilitation (CR). Furthermore, if this condition had an impact on the CR related functional improvement is not known. Our study has been designed to answer to both these questions.
  
  METHODS AND RESULTS:
  The study included 938 ACS/CCS patients who attended the CR program at the Niguarda Hospital (Milan). Extreme CV patients were defined as the presence of a previous CV events within 2 years or the presence of peripheral arteriopathy or the presence of a multivessel coronary involvement. Functional improvement was evaluated through 6-Minute Walking Test (6-MWT). As many as 26.9% of the patients had an extreme CV risk. They were older (67.8 ± 10.4 vs 64.1 ± 11.1 years; p ? 0.001), had a higher prevalence of CV risk factors and comorbidities and had a lower functional improvement during CR (102.9 ± 68.6 vs 138.1 ± 86.5 m; p ? 0.001). Extreme CV risk present a significant association with the 6-MWT results at multivariate analysis.
  
  CONCLUSION:
  Extreme CV risk is a very frequent condition among patients with ACS/CCS reaching the prevalence of 26.9%. Furthermore, being at extreme CV risk adversely affects the patient's functional improvement obtained during CR.
  
  Copyright © 2024. Published by Elsevier B.V.
  
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• Uric acid and metabolic syndrome: Importance of hyperuricemia cut-off.
  Int J Cardiol

  2024 Dec;417():132527. doi: 10.1016/j.ijcard.2024.132527.
  
  Maloberti Alessandro, Tognola Chiara, Garofani Ilaria, Algeri Michela, Shkodra Atea, Bellantonio Valentina, Le Van Marco, Pedroli Stefano, Campana Marta, Toscani Giorgio, Bombelli Michele, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  The relationship between HyperUricemia (HU) and Metabolic Sindrome (MS) and if Uric Acid (UA) should be inserted into MS definitions is a matter of debate. Aim of our study was to evaluate the correlation between UA and HU with Insulin Resistance (IR) and MS in a population of hypertensive patients. HU was defined with two cut-offs (the classic one of ?6 mg/dL for women and ? 7 for men; the newly proposed URRAH one with ?5.6 mg/dL for both sexes).
  
  METHODS:
  We enrolled 473 Hypertensive patients followed by the Hypertension Unit of San Gerardo Hospital (Monza, Italy). IR was defined through TG/HDL ratio and NCEP-ATP-III criteria were used for MS diagnosis.
  
  RESULTS:
  MS was found in 33.6 % while HU affected 14.8 % of subjects according to the traditional cut-off and 35.9 % with the URRAH cut-off. 9.7 % (traditional cut-off) and 17.3 % (URRAH's threshold) of the subjects had both HU and MS. UA level was significantly higher in MS group (5.7 vs 4.9 mg/dL, p 
  CONCLUSIONS:
  The main finding of our study is that UA and HU significantly relate to IR and MS. The higher the values of UA and the higher the cut-off used, the higher the strength of the relationship.
  
  Copyright © 2024. Published by Elsevier B.V.
  
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• Cardiac amyloidosis red flags: What all the cardiologist have to know.
  Int J Cardiol Cardiovasc Risk Prev

  2024 Jun;21():200271. doi: 200271.
  
  Maloberti Alessandro, Ciampi Claudio, Politi Francesco, Fabbri Saverio, Musca Francesco, Giannattasio Cristina
  
  Abstract
  
  Cardiac amyloidosis is becoming increasingly important among cardiologist and an early diagnosis is very important. Amyloidosis is a systemic disease and many cardiac and extracardiac elements (red flags) should raise the suspicion of the disease. Electrocardiographic and imaging techniques (such as echocardiography, cardiac magnetic resonance and scintigraphy) are useful tools to make a diagnosis together with the presence of orthopedic issues, peripheral neuropathy or plasma cell dyscrasia. Cardiac amyloidosis is also often associated with valvular disorder, heart failure or cardiomyopathy. Red flags are crucial to raise suspicion and reach an early diagnosis, in order to start a targeted treatment strategy that could change the patient's outcome. Indeed, in the last years four new drugs were approved to treat transthyretin amyloidosis.
  
  © 2024 The Author(s).
  
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• Treatment of obesity with liraglutide in cardiovascular prevention: Case series by the "ITACARE-P Light-Heart Lab" working group.
  Int J Cardiol Cardiovasc Risk Prev

  2024 Jun;21():200272. doi: 200272.
  
  Maranta Francesco, Buffoli Francesca, Giudici Vittorio, Malfatto Gabriella, Maloberti Alessandro, Maresca Luigi, Passaretti Bruno, Torri Anna, Turato Roberto, Ambrosetti Marco
  
  
  
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• Hyperuricemia in Cardiac Rehabilitation Patients: Prevalence and Association with Functional Improvement and Left Ventricular Ejection Fraction.
  High Blood Press Cardiovasc Prev

  2024 Sep;31(5):461-471. doi: 10.1007/s40292-024-00665-x.
  
  Fortuna Matteo, Tognola Chiara, Algeri Michela, Shkodra Atea, Intravaia Rita Cristina Myriam, Pezzoli Stefano, Garofani Ilaria, Morelli Martina, Gualini Elena, Fabbri Saverio, Sciume Luciana, Riccobono Salvatore, Beretta Giovanna, Giannattasio Cristina, Maloberti Alessandro
  
  Abstract
  
  INTRODUCTION:
  The role of uric acid (UA) and Hyper Uricemia (HU) in cardiac rehabilitation (CR) patients have been very little studied.
  
  AIM:
  To evaluate the prevalence of HU and if it is associated to the functional improvement obtained or the left ventricular Ejection Fraction (EF) in CR patients after Acute or Chronic Coronary Syndrome (ACS and CCS respectively).
  
  METHODS:
  We enrol 411 patients (62.4 ± 10.2 years; males 79.8%) enrolled in the CR program at Niguarda Hospital (Milan) from January 2012 to May 2023. HU was defined both as the classic cut-off (> 6 for females, > 7 mg/dL for males) and with the newly identified one by the URRAH study (> 5.1 for females, > 5.6 mg/dL for males). All patients performed a 6MWT and an echocardiography at the beginning and at the end of CR program.
  
  RESULTS:
  Mean UA values were within the normal range (5.6 ± 1.4 mg/dL) with 19.5% (classic cut-off) HU patients with an increase to 47.4% with the newer one. Linear regression analysis showed no role for UA in determining functional improvement, while UA and hyperuricemia (classic cut-off) were associated to admission and discharge EF. The same was not with the URRAH cut-off.
  
  CONCLUSIONS:
  HU is as frequent in CR patients as in those with ACS and CCS. UA didn't correlate with functional recovery while it is associated with admission and discharge EF as also is for HU (classic cut-off). Whit the URRAH cut-off HU prevalence increases significantly, however, it doesn't show any significant association with EF.
  
  © 2024. The Author(s).
  
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• [Substance abuse and cardiovascular risk: energy drinks].
  G Ital Cardiol (Rome)

  2024 Aug;25(8):546-556. doi: 10.1714/4309.42924.
  
  Ciliberti Giuseppe, Abrignani Maurizio Giuseppe, Zilio Filippo, Temporelli Pier Luigi, Ciccirillo Francesco, Fortuni Federico, Binaghi Giulio, Iannopollo Gianmarco, Cappelletto Chiara, Albani Stefano, Maloberti Alessandro, Ceriello Laura, Musella Francesca, Manfredi Roberto, Scicchitano Pietro, Riccio Carmine, Grimaldi Massimo, Gabrielli Domenico, Colivicchi Furio, Oliva Fabrizio,
  
  Abstract
  
  The consumption of energy drinks (ED) has become a growing public health issue, since potentially ED-related serious adverse cardiovascular events, including arrhythmias, myocardial infarction, cardiomyopathies, and sudden cardiac death, have been reported in recent years. The substances contained in ED include caffeine, taurine, sugars, B group vitamins and phyto-derivatives, which, especially if taken in large quantities and in a short amount of time, could cause serious side effects through various mechanisms of action, such as increased blood pressure and QT interval prolongation. Although there are still many open questions on ED that require further specific investigations, there is an urgent need for information and educational plans to the population, as well as for regulatory actions, particularly regarding transparency of substances and possible adverse effects.
  
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• Arrhythmic Risk Stratification in Cardiac Amyloidosis: A Review of the Current Literature.
  J Cardiovasc Dev Dis

  2024 Jul;11(7):. doi: 222.
  
  Bonvicini Eleonora, Preda Alberto, Tognola Chiara, Falco Raffaele, Gidiucci Roberto, Leo Giulio, Vargiu Sara, Varrenti Marisa, Gigli Lorenzo, Baroni Matteo, Carbonaro Marco, Colombo Giulia, Maloberti Alessandro, Giannattasio Cristina, Mazzone Patrizio, Guarracini Fabrizio
  
  Abstract
  
  Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients' functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.
  
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• Risk of Cardiovascular Events in Metabolically Healthy Overweight or Obese Adults: Role of LDL-Cholesterol in the Stratification of Risk.
  Diagnostics (Basel)

  2024 Jun;14(13):. doi: 1314.
  
  Palatini Paolo, Virdis Agostino, Masi Stefano, Mengozzi Alessandro, Casiglia Edoardo, Tikhonoff Valerie, Cicero Arrigo F G, Ungar Andrea, Parati Gianfranco, Rivasi Giulia, Salvetti Massimo, Barbagallo Carlo Maria, Bombelli Michele, Dell'Oro Raffaella, Bruno Berardino, Lippa Luciano, D'Elia Lanfranco, Masulli Maria, Verdecchia Paolo, Reboldi Gianpaolo, Angeli Fabio, Cianci Rosario, Mallamaci Francesca, Cirillo Massimo, Rattazzi Marcello, Cirillo Pietro, Gesualdo Loreto, Russo Elisa, Mazza Alberto, Giannattasio Cristina, Maloberti Alessandro, Volpe Massimo, Tocci Giuliano, Iaccarino Guido, Nazzaro Pietro, Galletti Ferruccio, Ferri Claudio, Desideri Giovambattista, Viazzi Francesca, Pontremoli Roberto, Muiesan Maria Lorenza, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged
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• Results of a Telehealth Program in Patients with Cardiovascular Risk Factors in low and Middle-Income Countries.
  High Blood Press Cardiovasc Prev

  2024 Sep;31(5):513-515. doi: 10.1007/s40292-024-00661-1.
  
  Ciuffarella Claudia, Maloberti Alessandro, Quarti-Trevano Fosca, Dell'Oro Raffaella, Facchetti Rita, Grassi Guido
  
  
  
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• Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.
  Metabolites

  2024 Jun;14(6):. doi: 323.
  
  Agabiti Rosei Claudia, Paini Anna, Buso Giacomo, Maloberti Alessandro, Giannattasio Cristina, Salvetti Massimo, Casiglia Edoardo, Tikhonoff Valerie, Angeli Fabio, Barbagallo Carlo Maria, Bombelli Michele, Cappelli Federica, Cianci Rosario, Ciccarelli Michele, Cicero Arrigo Francesco Giuseppe, Cirillo Massimo, Cirillo Pietro, Dell'Oro Raffaella, D'Elia Lanfranco, Desideri Giovambattista, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Grassi Guido, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Masi Stefano, Masulli Maria, Mazza Alberto, Mengozzi Alessandro, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Russo Elisa, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Virdis Agostino, Muiesan Maria Lorenza, Borghi Claudio,
  
  Abstract
  
  High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ? 150 mg/dL. Higher levels of SUA (hSUA) were defined as ?5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27],
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• Strike early-strike strong lipid-lowering strategy with proprotein convertase subtilisin/kexin type 9 inhibitors in acute coronary syndrome patients: real-world evidence from the AT-TARGET-IT registry.
  Eur J Prev Cardiol

  2024 Nov;31(15):1806-1816. doi: 10.1093/eurjpc/zwae170.
  
  Gargiulo Paola, Basile Christian, Galasso Gennaro, Bellino Michele, D'Elia Debora, Patti Giuseppe, Bosco Manuel, Prinetti Matteo, Andò Giuseppe, Campanella Francesca, Taverna Giovanni, Calabrò Paolo, Cesaro Arturo, Fimiani Fabio, Catalano Angelo, Varbella Ferdinando, Corleto Antonella, Barillà Francesco, Muscoli Saverio, Musumeci Giuseppe, Delnevo Fabrizio, Giallauria Francesco, Napoli Raffaele, Porto Italo, Polimeni Alberto, Quarta Rossella, Maloberti Alessandro, Merlini Piera Angelica, De Luca Leonardo, Casu Gavino, Brunetti Natale Daniele, Crisci Mario, Paloscia Leonardo, Bilato Claudio, Indolfi Ciro, Marzano Federica, Fontanarosa Sara, Buonocore Davide, Parlati Antonio Luca Maria, Nardi Ermanno, Prastaro Maria, Soricelli Andrea, Salvatore Marco, Paolillo Stefania, Perrone-Filardi Pasquale, Cuomo Gianluigi, Testa Crescenzo, Passaretti Gianluca, Vallefuoco Giuseppe, Romano Annalisa, Dell'Anno Raffaele, Merolla Aurora, Iannone Francesca Paola
  
  Abstract
  
  AIMS:
  No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in the real world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major cardiovascular (CV) events in the real world.
  
  METHODS AND RESULTS:
  The lipid control outcome was the percentage of patients reaching the LDL-C target of
  CONCLUSION:
  Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early-strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.
  
  © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site?for further information please contact journals.permissions@oup.com.
  
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• Cardiovascular Structural and Functional Parameters in Idiopathic Pulmonary Fibrosis at Disease Diagnosis.
  High Blood Press Cardiovasc Prev

  2024 May;31(3):289-297. doi: 10.1007/s40292-024-00638-0.
  
  Faverio Paola, Maloberti Alessandro, Rebora Paola, Intravaia Rita Cristina Myriam, Tognola Chiara, Toscani Giorgio, Amato Anna, Leoni Valerio, Franco Giovanni, Vitarelli Federica, Spiti Simona, Luppi Fabrizio, Valsecchi Maria Grazia, Pesci Alberto, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Prevalence of cardiac and vascular fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF) has not been extensively evaluated.
  
  AIM:
  In this study, we aimed to evaluate the heart and vessels functional and structural properties in patients with IPF compared to healthy controls. An exploratory analysis regarding disease severity in IPF patients has been done.
  
  METHODS:
  We enrolled 50 patients with IPF (at disease diagnosis before antifibrotic therapy initiation) and 50 controls matched for age and gender. Heart was evaluated through echocardiography and plasmatic NT-pro-brain natriuretic peptide that, together with patients' symptoms, allow to define the presence of Heart Failure (HF) and diastolic dysfunction. Vessels were evaluated through Flow Mediated Dilation (FMD - endothelial function) and Pulse Wave Velocity (PWV-arterial stiffness) RESULTS: Patients with IPF had a prevalence of diastolic disfunction of 83.8%, HF of 37.8% and vascular fibrosis of 76.6%. No statistically significant difference was observed in comparison to the control group who showed prevalence of diastolic disfunction, HF and vascular fibrosis of 67.3%, 24.5% and 84.8%, respectively. Disease severity seems not to affect PWV, FMD, diastolic dysfunction and HF.
  
  CONCLUSIONS:
  Patients with IPF early in the disease course do not present a significant CV fibrotic involvement when compared with age- and sex-matched controls. Bigger and adequately powered studies are needed to confirm our preliminary data and longitudinal studies are required in order to understand the time of appearance and progression rate of heart and vascular involvement in IPF subjects.
  
  © 2024. The Author(s).
  
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• Heart Failure with Preserved Ejection Fraction: How to Deal with This Chameleon.
  J Clin Med

  2024 Feb;13(5):. doi: 1375.
  
  Lucà Fabiana, Oliva Fabrizio, Abrignani Maurizio Giuseppe, Di Fusco Stefania Angela, Gori Mauro, Giubilato Simona, Ceravolo Roberto, Temporelli Pier Luigi, Cornara Stefano, Rao Carmelo Massimiliano, Caretta Giorgio, Pozzi Andrea, Binaghi Giulio, Maloberti Alessandro, Di Nora Concetta, Di Matteo Irene, Pilleri Anna, Gelsomino Sandro, Riccio Carmine, Grimaldi Massimo, Colivicchi Furio, Gulizia Michele Massimo
  
  Abstract
  
  Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.
  
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• Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.
  Metabolites

  2024 Mar;14(3):. doi: 164.
  
  D'Elia Lanfranco, Masulli Maria, Cirillo Pietro, Virdis Agostino, Casiglia Edoardo, Tikhonoff Valerie, Angeli Fabio, Barbagallo Carlo Maria, Bombelli Michele, Cappelli Federica, Cianci Rosario, Ciccarelli Michele, Cicero Arrigo F G, Cirillo Massimo, Dell'Oro Raffaella, Desideri Giovambattista, Ferri Claudio, Gesualdo Loreto, Giannattasio Cristina, Grassi Guido, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Maloberti Alessandro, Masi Stefano, Mazza Alberto, Mengozzi Alessandro, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Russo Elisa, Salvetti Massimo, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Borghi Claudio, Galletti Ferruccio,
  
  Abstract
  
  Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied ( = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.
  
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• [Multidistrict atherosclerotic disease: epidemiological and clinical framework].
  G Ital Cardiol (Rome)

  2024 Apr;25(4):239-251. doi: 10.1714/4244.42205.
  
  Di Fusco Stefania Angela, Abrignani Maurizio Giuseppe, Amico Antonio Francesco, Lucà Fabiana, Mureddu Gian Francesco, Ceravolo Roberto, Temporelli Pier Luigi, Acerbo Vincenzo, Altamura Vito, Baccino Danilo, Binaghi Giulio, Bugani Giulia, Cesaro Arturo, Ciccirillo Francesco, Cocozza Sara, D'Errigo Paola, Di Martino Mirko, Di Nora Concetta, Fileti Luca, Lopriore Vincenzo, Maloberti Alessandro, Monitillo Francesco, Gulizia Michele Massimo, Grimaldi Massimo, Gabrielli Domenico, Oliva Fabrizio, Colivicchi Furio
  
  Abstract
  
  Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.
  
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• Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).
  J Clin Endocrinol Metab

  2024 Mar;():. doi: dgae170.
  
  D'Elia Lanfranco, Masulli Maria, Virdis Agostino, Casiglia Edoardo, Tikhonoff Valerie, Angeli Fabio, Barbagallo Carlo Maria, Bombelli Michele, Cappelli Federica, Cianci Rosario, Ciccarelli Michele, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Dell'Oro Raffaella, Desideri Giovambattista, Ferri Claudio, Gesualdo Loreto, Giannattasio Cristina, Grassi Guido, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Maloberti Alessandro, Masi Stefano, Mazza Alberto, Mengozzi Alessandro, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Russo Elisa, Salvetti Massimo, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Borghi Claudio, Galletti Ferruccio
  
  Abstract
  
  PURPOSE:
  Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk.
  
  METHODS:
  The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis.
  
  RESULTS:
  During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors.
  
  CONCLUSIONS:
  The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.
  
  © The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site?for further information please contact journals.permissions@oup.com.
  
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• Unveiling the gender gap in ST-elevation myocardial infarction: a retrospective analysis of a single Italian center gender disparities in STEMI-ACS.
  J Cardiovasc Med (Hagerstown)

  2024 Mar;25(3):239-242. doi: 10.2459/JCM.0000000000001594.
  
  Garatti Laura, Tavecchia Giovanni, Milani Martina, Rizzi Ilaria, Tondelli Daniele, Bernasconi Davide, Maloberti Alessandro, Oliva Fabrizio, Sacco Alice
  
  
  
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• Neurological hypertensive emergencies: Correlation of blood pressure values with in-hospital outcomes in ischemic stroke.
  Eur J Intern Med

  2024 Jun;124():61-68. doi: 10.1016/j.ejim.2024.01.029.
  
  Giani Valentina, Valobra Tommaso, Capsoni Nicolò, Galasso Michele, De Censi Lorenzo, Ferretti Cecilia, Sultana Andrea, Giacalone Annalisa, Garofani Ilaria, Bombelli Michele, Ceresa Chiara, Gheda Silvia, Agostoni Elio Clemente, Galbiati Filippo, Giannattasio Cristina, Maloberti Alessandro
  
  Abstract
  
  BACKGROUND:
  Few certainties exist regarding optimal management of Blood Pressure (BP) in the very first hours after an ischemic stroke and many questions remain still unanswered. Our work aimed to evaluate the role of BP and its trend as possible determinants of in-hospital mortality (primary outcome), discharge disabilities and hospitalization length (secondary outcomes) in ischemic stroke patients presented with Hypertensive Emergencies (HE).
  
  METHODS:
  We retrospectively evaluated patients presented to Niguarda Hospital, Emergency Department (ED), from 2015 to 2017 with a neurological ischemic HE. BP at ED presentation (T0), its management in ED (T1) and its values at the stroke unit admission (T2) were evaluated.
  
  RESULTS:
  267 patients were included (0.13 % of all ED accesses and 17.9 % of all ischemic strokes). In the whole population, BP values were not associated with in-hospital mortality while T0 and T2 SBP result were associated to discharge disability and hospitalization length. In pre-specified subgroup analysis these associations were confirmed only in untreated subjects (not anti-hypertensive nor thrombolysis). In fact, no significant relationship can be found between BP values and any secondary outcome in thrombolysis and anti-hypertensive treated patients.
  
  CONCLUSIONS:
  BP values and its management can not be related to in-hospital mortality in stroke patients, presented with HE, while they are associated to discharge disability and hospitalization length. In subgroup analysis, results were confirmed only in untreated (not anti-hypertensive therapies nor thrombolytic).
  
  Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.
  J Am Heart Assoc

  2024 Feb;13(3):e030319. doi: e030319.
  
  Tikhonoff Valérie, Casiglia Edoardo, Virdis Agostino, Grassi Guido, Angeli Fabio, Arca Marcello, Barbagallo Carlo M, Bombelli Michele, Cappelli Federica, Cianci Rosario, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Dell'oro Raffaella, D'elia Lanfranco, Desideri Giovambattista, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Mallamaci Francesca, Maloberti Alessandro, Masi Stefano, Masulli Maria, Mazza Alberto, Mengozzi Alessandro, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Russo Elisa, Salvetti Massimo, Temporelli Pier Luigi, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Borghi Claudio
  
  Abstract
  
  BACKGROUND:
  Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort.
  
  METHODS AND RESULTS:
  Among 14?189 subjects aged 18 to 95?years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150?mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139?375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89?mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1,
  CONCLUSIONS:
  Lower (89?mg/dL) than conventional (150?mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.
  
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• Hyperkalaemia in Cardiological Patients: New Solutions for an Old Problem.
  Cardiovasc Drugs Ther

  2024 Jan;():. doi: 10.1007/s10557-024-07551-7.
  
  Abrignani Maurizio Giuseppe, Gronda Edoardo, Marini Marco, Gori Mauro, Iacoviello Massimo, Temporelli Pier Luigi, Benvenuto Manuela, Binaghi Giulio, Cesaro Arturo, Maloberti Alessandro, Tinti Maria Denitza, Riccio Carmine, Colivicchi Furio, Grimaldi Massimo, Gabrielli Domenico, Oliva Fabrizio,
  
  Abstract
  
  Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease. Mortality, cardiovascular morbidity, and hospitalisation are higher in patients with hyperkalaemia. Hyperkalaemia represents a major contraindication or a withholding cause for disease-modifying therapies like renin-angiotensin-aldosterone inhibitors (RAASi), mainly mineralocorticoid receptor antagonists. Hyperkalaemia can be also classified as acute and chronic, according to the onset. Acute hyperkalaemia is often a life-threatening emergency requiring immediate treatment to avoid lethal arrhythmias. Therapy goal is cell membrane stabilisation by calcium administration, cellular intake, shift of extracellular potassium to the intracellular space (insulin, beta-adrenergic agents, sodium bicarbonate), and increased elimination with diuretics or dialysis. Chronic hyperkalaemia was often managed with dietary counselling to prevent potassium-rich food intake and tapering of potassium-increasing drugs, mostly RAASi. Sodium polystyrene sulphonate, a potassium binder, was the only therapeutic option. Recently, new drugs such as patiromer and sodium zirconium cyclosilicate give new opportunities for the treatment of hyperkalaemia, as they proved to be safe, well tolerated, and effective. Aim of this review is to describe the burden of hyperkalaemia in cardiovascular patients, its direct and indirect effects, and the therapeutic options now available in the acute and chronic setting.
  
  © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
  
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• [Lipoprotein(a): relationships with atherosclerosis and valvular heart disease, and emerging therapies].
  G Ital Cardiol (Rome)

  2024 Feb;25(2):76-87. doi: 10.1714/4187.41756.
  
  Abrignani Maurizio Giuseppe, Maloberti Alessandro, Di Fusco Stefania Angela, Lucà Fabiana, Cesaro Arturo, Acerbo Vincenzo, Fabbri Saverio, Di Matteo Irene, Amico Antonio F, Temporelli Pier Luigi, Riccio Carmine, Colivicchi Furio, Grimaldi Massimo, Gabrielli Domenico, Oliva Fabrizio
  
  Abstract
  
  Lipoprotein(a) [Lp(a)] is a well-established cardiovascular risk factor, whose relationship with atherosclerotic disease has been confirmed by epidemiological, genome-wide association, Mendelian randomization, and meta-analysis studies. This association is determined by its pro-atherogenic, pro-thrombotic and pro-inflammatory properties. Lp(a) is the most common monogenic risk factor for atherosclerosis, with a prevalence of about 1 in 5 people. Recently, its etiopathogenetic relationship with calcific and degenerative valvular heart diseases, particularly with aortic and mitral stenosis, has been suspected. It has not yet been demonstrated whether its reduction translates into a lower risk of cardiovascular events. Up to now, Lp(a) has been considered a non-modifiable risk factor, as current lipid-lowering drugs have limited effects on its levels. New specific lipid-lowering therapies with high efficacy in reducing circulating Lp(a) levels are being investigated in randomized trials; however, the effects of this reduction on cardiovascular outcomes are still being studied.
  
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• Secondary Prevention and Extreme Cardiovascular Risk Evaluation (SEVERE-1), Focus on Prevalence and Associated Risk Factors: The Study Protocol.
  High Blood Press Cardiovasc Prev

  2023 Nov;30(6):573-583. doi: 10.1007/s40292-023-00607-z.
  
  Maloberti Alessandro, Intravaia Rita Cristina Myriam, Mancusi Costantino, Cesaro Arturo, Golia Enrica, Ilaria Fucile, Coletta Silvio, Merlini Piera, De Chiara Benedetta, Bernasconi Davide, Algeri Michela, Ossola Paolo, Ciampi Claudio, Riccio Alfonso, Tognola Chiara, Ardissino Maddalena, Inglese Elvira, Scaglione Francesco, Calabrò Paolo, De Luca Nicola, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Despite significant improvement in secondary CardioVascular (CV) preventive strategies, some acute and chronic coronary syndrome (ACS and CCS) patients will suffer recurrent events (also called "extreme CV risk"). Recently new biochemical markers, such as uric acid (UA), lipoprotein A [Lp(a)] and several markers of inflammation, have been described to be associated with CV events recurrence. The SEcondary preVention and Extreme cardiovascular Risk Evaluation (SEVERE-1) study will accurately characterize extreme CV risk patients enrolled in cardiac rehabilitation (CR) programs.
  
  AIM:
   Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors.
  
  AIM:
  Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors.
  
  METHODS:
  We will prospectively enrol 730 ACS/CCS patients at the beginning of a CR program. Extreme CV risk will be retrospectively defined as the presence of a previous (within 2 years) CV events in the patients' clinical history. UA, Lp(a) and inflammatory markers (interleukin-6 and -18, tumor necrosis factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with those without extreme CV risk but also with two control groups: 1180 hypertensives and 765 healthy subjects. The association between these biomarkers and extreme CV risk will be assessed with a multivariable model and two scoring systems will be created for an accurate identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce the biochemical markers. Finally, by exome sequencing we will both evaluate polygenic risk score ability to predict recurrent events and perform mendellian randomization analysis on CV biomarkers.
  
  CONCLUSIONS:
  Our study proposal was granted by the European Union PNRR M6/C2 call. With this study we will give definitive data on extreme CV risk prevalence rising attention on this condition and leading cardiologist to do a better diagnosis and to carry out a more intensive treatment optimization that will finally leads to a reduction of future ACS recurrence. This will be even more important for cardiologists working in CR that is a very important place for CV risk definition and therapies refinement.
  
  © 2023. The Author(s).
  
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• Long-term increase in serum uric acid and its predictors over a 25 year follow-up: Results of the PAMELA study.
  Nutr Metab Cardiovasc Dis

  2024 Jan;34(1):223-229. doi: 10.1016/j.numecd.2023.10.009.
  
  Maloberti Alessandro, Dell'Oro Raffaella, Bombelli Michele, Quarti-Trevano Fosca, Facchetti Rita, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  BACKGROUND AND AIMS:
  Hyperuricemia (HU) has been shown to be associated with an adverse impact on cardiovascular and metabolic risk. Scanty data are available in the general population on the longitudinal changes in serum uric acid (SUA), the occurrence of HU and their potential predictors. We examined during a 25-year follow-up the SUA changes and the factors associated with HU development in the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study.
  
  METHODS AND RESULTS:
  We analyzed data collected in 561 subjects of the PAMELA study evaluated during an average follow-up time amounting to 25.4 ± 1.0 years (mean ± SD). HU was defined by the Uric Acid Right for Heart Health (URRAh) cutoff (5.1 for females and 5.6 mg/dl for males). Mean SUA values during follow-up increased from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dl (P
  CONCLUSION:
  The present study provides longitudinal evidence that in the general population during a 25 year follow-up there is a progressive increase in SUA and HU development. Baseline SUA represents the most important factor associated with these modifications. Gender, renal dysfunction, triglycerides, obesity, diuretic treatment and blood pressure represent other variables capable to predict future occurrence of HU.
  
  Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
  
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• The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.
  High Blood Press Cardiovasc Prev

  2023 Sep;30(5):411-425. doi: 10.1007/s40292-023-00602-4.
  
  Maloberti Alessandro, Mengozzi Alessandro, Russo Elisa, Cicero Arrigo Francesco Giuseppe, Angeli Fabio, Agabiti Rosei Enrico, Barbagallo Carlo Maria, Bernardino Bruno, Bombelli Michele, Cappelli Federica, Casiglia Edoardo, Cianci Rosario, Ciccarelli Michele, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'Elia Lanfranco, Dell'Oro Raffaella, Facchetti Rita, Ferri Claudio, Galletti Ferruccio, Giannattasio Cristina, Gesualdo Loreto, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Masi Stefano, Masulli Maria, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Parati Gianfranco, Palatini Paolo, Pauletto Paolo, Pontremoli Roberto, Pugliese Nicola Riccardo, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Salvetti Massimo, Tikhonoff Valerie, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Virdis Agostino, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.
  
  © 2023. The Author(s).
  
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• [How to overcome barriers to implementation of prevention and management strategies of atherosclerotic cardiovascular disease through lipid-lowering therapy].
  G Ital Cardiol (Rome)

  2023 Oct;24(10):770-780. doi: 10.1714/4100.40977.
  
  Arca Marcello, Averna Maurizio, Borghi Claudio, Lettino Maddalena, Perrone Filardi Pasquale, Alberti Antonia, Bilato Claudio, Calabrò Paolo, Carubbi Francesca, Ciccone Marco Matteo, Cipollone Francesco, Citroni Nadia, De Luca Leonardo, Giaccari Andrea, Iannuzzo Gabriella, Maloberti Alessandro, Marcucci Rossella, Pignatelli Spinazzola Pasquale, Pirro Matteo, Pisciotta Livia, Sarullo Filippo, Sciacqua Angela, Suppressa Patrizia, Varbella Ferdinando, Werba José Pablo, Zambon Alberto
  
  Abstract
  
  Atherosclerotic cardiovascular diseases remain the main cause of mortality worldwide, due to a poor control of modifiable risk factors for atherosclerosis. High levels of low-density lipoprotein cholesterol represent the most relevant actor in the development of atherosclerotic cardiovascular diseases, as well as the main target of prevention strategies. Although lipid-lowering treatments were shown to be effective for cardiovascular prevention, several barriers (e.g. clinician reluctance to prescribe an intensive treatment, poor adherence of patients to therapy, high pharmacotherapy burden of high-risk patients and the fear for adverse events potentially associated with statins) still prevent therapy optimization. Such issues will be addressed in this review article, taking into account possible strategies for their solution, through an integrated approach including both management interventions and a larger use of the available pharmacologic options.
  
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• Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios.
  J Clin Med

  2023 Sep;12(18):. doi: 5955.
  
  Lucà Fabiana, Oliva Fabrizio, Abrignani Maurizio Giuseppe, Di Fusco Stefania Angela, Parrini Iris, Canale Maria Laura, Giubilato Simona, Cornara Stefano, Nesti Martina, Rao Carmelo Massimiliano, Pozzi Andrea, Binaghi Giulio, Maloberti Alessandro, Ceravolo Roberto, Bisceglia Irma, Rossini Roberta, Temporelli Pier Luigi, Amico Antonio Francesco, Calvanese Raimondo, Gelsomino Sandro, Riccio Carmine, Grimaldi Massimo, Colivicchi Furio, Gulizia Michele Massimo
  
  Abstract
  
  It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.
  
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• Effectiveness and Safety of Remdesivir in Treating Hospitalised Patients with COVID-19: A Propensity Score Analysis of Real-Life Data from a Monocentric Observational Study in Times of Health Emergency.
  Clin Drug Investig

  2023 Oct;43(10):763-771. doi: 10.1007/s40261-023-01304-4.
  
  Ughi Nicola, Bernasconi Davide Paolo, Del Gaudio Francesca, Dicuonzo Armanda, Maloberti Alessandro, Giannattasio Cristina, Tarsia Paolo, Travi Giovanna, Scaglione Francesco, Colombo Fabrizio, Bertuzzi Michaela, Adinolfi Antonella, Valsecchi Maria Grazia, Rossetti Claudio, Epis Oscar Massimiliano,
  
  Abstract
  
  BACKGROUND AND OBJECTIVES:
  Remdesivir is an antiviral agent, which was shown to be safe and effective in treating early COVID-19, but its favourable impact in hospitalised patients with non-critical disease is still under investigation. The present study aimed to assess the effectiveness and safety of remdesivir as a treatment for hospitalised patients with COVID-19 by a propensity score analysis of observational data.
  
  METHODS:
  In this monocentric retrospective cohort study, the effectiveness and safety of a 5-day course of remdesivir (200 mg intravenously at Day 1, then 100 mg from Days 2-5) in association with the standard of care were assessed in comparison with the standard of care only. The primary endpoint was the proportion of recovery on Day 14.
  
  RESULTS:
  Of 3662 eligible inpatients who tested positive for the severe acute respiratory syndrome coronavirus 2 genome by nasopharyngeal swab at admission, 861 (24%) non-critical patients were included in a propensity score analysis and 281 (33%) were exposed to remdesivir. In total, 242/281 (86.1%) and 435/580 (75.0%) patients recovered in exposed and non-exposed, respectively, with a relative improvement of 11.1% (95% CI + 5.8 to 16.5%; unadjusted odds ratio: 2.07, 95% CI 1.40-3.05, p = 0.0001; after adjustment by propensity score weighting, odds ratio: 1.92, 95% CI 1.30-2.83, p = 0.001). In treated patients, 1 (0.03%) anaphylactic reaction and 1 (0.03%) acute reaction during drug injection were reported, and 24 (8.5%) patients stopped the treatment due to adverse reactions. No significant differences were found with respect to the secondary efficacy endpoints (in-hospital all-cause death, need for intensive care treatments, clinical improvement score at Day 28) and safety endpoints (any and serious adverse reactions).
  
  CONCLUSION:
  A 5-day course of remdesivir in association with the standard of care effectively promoted recovery from COVID-19 among non-critical in-hospital patients and had an acceptable safety profile.
  
  © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
  
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• Natural history and clinical burden of moderate aortic stenosis: a systematic review and explorative meta-analysis.
  J Cardiovasc Med (Hagerstown)

  2023 Sep;24(9):659-665. doi: 10.2459/JCM.0000000000001490.
  
  Morelli Martina, Galasso Michele, Esposito Giuseppe, Soriano Francesco Stefano, Nava Stefano, Da Pozzo Caterina, Bossi Irene, Piccaluga Emanuela, Bruschi Giuseppe, Maloberti Alessandro, Oliva Fabrizio, Oreglia Jacopo Andrea, Giannattasio Cristina, Montalto Claudio
  
  Abstract
  
  AIMS:
  The mortality risk of patients with moderate aortic stenosis is not well known, but recent studies suggested that it might negatively affect prognosis. We aimed to assess the natural history and clinical burden of moderate aortic stenosis and to investigate the interaction of patients' baseline characteristics with prognosis.
  
  METHODS:
  Systematic research was conducted on PubMed. The inclusion criteria were inclusion of patients with moderate aortic stenosis; and report of the survival at 1-year follow-up (minimum). Incidence ratios related to all-cause mortality in patients and controls of each study were estimated and then pooled using a fixed effects model. All patients with mild aortic stenosis or without aortic stenosis were considered controls. Meta-regression analysis was performed to assess the impact of left ventricular ejection fraction and age on the prognosis of patients with moderate aortic stenosis.
  
  RESULTS:
  Fifteen studies and 11?596 patients with moderate aortic stenosis were included. All-cause mortality was significantly higher among patients with moderate aortic stenosis than in controls in all timeframes analysed (all P ?0.0001). Left ventricular ejection fraction and sex did not significantly impact on the prognosis of patients with moderate aortic stenosis ( P ?=?0.4584 and P ?=?0.5792), while increasing age showed a significant interaction with mortality (estimate = 0.0067; 95% confidence interval: 0.0007-0.0127; P ?=?0.0323).
  
  CONCLUSION:
  Moderate aortic stenosis is associated with reduced survival. Further studies are necessary to confirm the prognostic impact of this valvulopathy and the possible benefit of aortic valve replacement.
  
  Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.
  
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• Elevated Serum Urea-to-Creatinine Ratio and In-Hospital Death in Patients with Hyponatremia Hospitalized for COVID-19.
  Biomedicines

  2023 May;11(6):. doi: 1555.
  
  Regolisti Giuseppe, Rebora Paola, Occhino Giuseppe, Lieti Giulia, Molon Giulio, Maloberti Alessandro, Algeri Michela, Giannattasio Cristina, Valsecchi Maria Grazia, Genovesi Simonetta
  
  Abstract
  
  Hyponatremia is associated with adverse outcomes in hospitalized patients. An elevated value of the serum urea-to-creatinine ratio (UCR) has been proposed as a proxy of hypovolemia. The aim of this study was to investigate the relationship between the UCR and in-hospital death in patients hospitalized with COVID-19 and hyponatremia. We studied 258 patients admitted for COVID-19 between January 2020 and May 2021 with serum sodium at 40 at baseline, a > 10 mmol/L increase in serum sodium values within the first week of hospitalization was associated with higher odds of in-hospital death (OR = 2.93, 95% CI: 1.03-8.36, = 0.044) compared to patients who experienced a 10 mmol/L increase in serum sodium within the first week of hospital stays may further worsen the in-hospital prognosis.
  
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• Uric acid significantly correlates with the presence of low-voltage areas at the endocardial mapping in patients with non-valvular atrial fibrillation.
  Nutr Metab Cardiovasc Dis

  2023 Jul;33(7):1323-1329. doi: 10.1016/j.numecd.2023.05.002.
  
  Baroni Matteo, Fortuna Matteo, Maloberti Alessandro, Leidi Filippo, Ciampi Claudio Mario, Carbonaro Marco, Testoni Alessio, Vargiu Sara, Varrenti Marisa, Paolucci Marco, Gigli Lorenzo, Giannattasio Cristina, Mazzone Patrizio
  
  Abstract
  
  BACKGROUND AND AIMS:
  Interest in the role of atrial substrate in maintaining Atrial Fibrillation (AF) is growing. Fibrosis is the culprit in the electrical derangement of the myocytes. Many cardiovascular risk factors are known to be linked to atrial scarring; among them Uric Acid (UA) is emerging. The purpose of our study is to find whether UA is associated with Left Atrium (LA) with pathological substrate.
  
  METHODS AND RESULTS:
  81 patients who underwent radiofrequency transcatheter ablation for nonvalvular AF at the cardiological department of the Niguarda Hospital were enrolled in an observational, cross-sectional, single-center study. UA levels were analysed before the procedure. High density electroanatomic mapping of the LA was performed and patients were divided according to the presence or not of areas of pathological substrate (bipolar voltage
  CONCLUSIONS:
  In a population of patients who underwent AF ablation, higher UA levels were significantly associated with pathological LA substrate at electro-anatomical mapping.
  
  Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• [Substances of abuse and cardiovascular risk: cannabinoids].
  G Ital Cardiol (Rome)

  2023 Jun;24(6):455-465. doi: 10.1714/4041.40205.
  
  Abrignani Maurizio G, Ciccirillo Francesco, Temporelli Pier Luigi, Cesaro Arturo, Binaghi Giulio, Maloberti Alessandro, Cappelletto Chiara, Oliva Fabrizio, Riccio Carmine, Caldarola Pasquale, Gabrielli Domenico, Colivicchi Furio
  
  Abstract
  
  Progressive legalization for medical conditions or recreational use has led to an increased use of cannabis and synthetic cannabinoids over the past years. Most consumers are young and healthy, without cardiovascular risk factors; however, this population is expected to include older individuals. Thus, concerns have arisen about safety and short- and long-term potential adverse effects, with special emphasis on vulnerable groups. Studies show that cannabis might be linked with thrombosis, inflammation, and atherosclerosis, and many reports have associated cannabis and synthetic cannabinoids use with serious adverse cardiovascular complications, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest. A clearly defined causal role cannot be demonstrated, because of confounding variables. Physicians need to become aware of the possible spectrum of clinical presentations, not only for timely diagnosis and treatment, but also for effective counseling and prevention.In this review, we aim to provide a basic understanding of the physiological effects of cannabis, the role of the endocannabinoid system in cardiovascular disease, and the cardiovascular consequences of cannabis and synthetic cannabinoid use, including a comprehensive review of the studies and case reports that provide supportive evidence for cannabis as a trigger of adverse cardiovascular events according to the current literature.
  
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• Serum uric acid and left ventricular mass index independently predict cardiovascular mortality: The uric acid right for heart health (URRAH) project.
  Eur J Intern Med

  2023 Aug;114():58-65. doi: 10.1016/j.ejim.2023.04.010.
  
  Muiesan Maria Lorenza, Agabiti Rosei Claudia, Paini Anna, Casiglia Edoardo, Cirillo Massimo, Grassi Guido, Iaccarino Guido, Mallamaci Francesca, Maloberti Alessandro, Mazza Alberto, Mengozzi Alessandro, Palatini Paolo, Parati Gianfranco, Reboldi Gianpaolo, Rivasi Giulia, Russo Elisa, Salvetti Massimo, Tikhonoff Valerie, Tocci Giuliano, Borghi Claudio,
  
  Abstract
  
  UNLABELLED:
  A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study.
  
  AIM:
  of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death.
  
  METHODS:
  Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men.
  
  RESULTS:
  A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P
  CONCLUSIONS:
  Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women.
  
  Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Impact of the Increase in Left Ventricular Mass on the Risk of Long-Term Cardiovascular Mortality: A Prospective Cohort Study.
  Hypertension

  2023 Jun;80(6):1321-1330. doi: 10.1161/HYPERTENSIONAHA.122.19988.
  
  Bombelli Michele, Vanoli Jennifer, Facchetti Rita, Maloberti Alessandro, Cuspidi Cesare, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular events, and evidence has been obtained that an increase of a normal left ventricular mass (LVM) or new-onset LVH over time augments cardiovascular outcomes.
  
  METHODS:
  We addressed this issue in a sample of a general population at relatively low cardiovascular risk. We analyzed subjects with normal echocardiographic LVM enrolled in the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study to follow the increase of LVM over time and assess the prognostic impact of this change on the incidence of cardiovascular events (mean follow-up 18.5 years).
  
  RESULTS:
  In 990 subjects with no LVH at baseline, there was a significant average increase of LVM (21.2%), LVMI (18.9%), and LVMI (22.3%) more than 10 years later. About a quarter developed LVH. The LVMI change exhibited an association with the cardiovascular risk mortality during the following 18.5 years, and the association remained significant after adjustment for confounders (hazard ratio, 1.2 [1.0-1.5]). Similar findings were obtained for LVM in absolute values or indexed for height. The association was seen in both genders, but the link with the cardiovascular risk was statistically significant in males only.
  
  CONCLUSIONS:
  Thus, although over 10 years, the LVM increase does not reach a LVH status, it is associated with an augmented cardiovascular mortality risk. This suggests that it might be important to consider periodical LVM assessment, even when LVM is within the normal range, to timely detect its increase and cope with the need of cardiovascular risk restratification.
  
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• The Key Role of a Psychoactive Substance Use History in Comprehensive Cardiovascular Risk Assessment, Diagnosis, Treatment, and Prevention.
  Cardiology

  2023 ;148(3):257-268. doi: 10.1159/000530246.
  
  Ciccirillo Francesco, Abrignani Maurizio G, Temporelli Pier Luigi, Binaghi Giulio, Cappelletto Chiara, Lopriore Vincenzo, Cesaro Arturo, Maloberti Alessandro, Cozzoli Danilo, Riccio Carmine, Caldarola Pasquale, Oliva Fabrizio, Gabrielli Domenico, Colivicchi Furio
  
  Abstract
  
  BACKGROUND:
  Psychoactive substances have toxic effects resulting different cardiovascular and non-cardiovascular organ damage. Through a variety of mechanisms, they can trigger the onset of various forms of cardiovascular disease: acute or chronic, transient or permanent, subclinical or symptomatic. Hence, a thorough knowledge of the patient's drug habits is essential for a more complete clinical-etiopathogenetic diagnosis and consequent therapeutic, preventive, and rehabilitative management.
  
  SUMMARY:
  The prime reason for taking a psychoactive substance use history in the cardiovascular context is to identify those people who use substances (whether habitual or occasional users, symptomatic or not) and adequately assess their overall cardiovascular risk profile in terms of "user status" and type of substance(s) used. A psychoactive substance history could also alert the physician to suspect, and eventually diagnose, cardiovascular disease related to the intake of psychoactive substances, so optimizing the medical management of users. This anamnesis could finally assess the likelihood of patients persisting in the habit as a user or relapse, while maintaining high their cardiovascular risk profile. Taking such a history should be mandatory when a causal connection is suspected between intake of psychoactive substances and the observed symptoms or pathology, regardless of whether the individual is a declared user or not.
  
  KEY MESSAGES:
  The purpose of this article was to provide practical information on when, how, and why to perform a psychoactive substance use history.
  
  © 2023 S. Karger AG, Basel.
  
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• Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study.
  Metabolites

  2023 Feb;13(2):. doi: 244.
  
  Mengozzi Alessandro, Pugliese Nicola Riccardo, Desideri Giovambattista, Masi Stefano, Angeli Fabio, Barbagallo Carlo Maria, Bombelli Michele, Cappelli Federica, Casiglia Edoardo, Cianci Rosario, Ciccarelli Michele, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Dell'Oro Raffaella, D'Elia Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Grassi Guido, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Maloberti Alessandro, Masulli Maria, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Russo Elisa, Salvetti Massimo, Tikhonoff Valerie, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Borghi Claudio, Virdis Agostino,
  
  Abstract
  
  High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (?4.7 mg/dL) and CVM (?5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40],
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• Hypertensive emergencies and urgencies: a preliminary report of the ongoing Italian multicentric study ERIDANO.
  Hypertens Res

  2023 Jun;46(6):1570-1581. doi: 10.1038/s41440-023-01232-y.
  
  Vallelonga Fabrizio, Cesareo Marco, Menon Leonardo, Leone Dario, Lupia Enrico, Morello Fulvio, Totaro Silvia, Aggiusti Carlo, Salvetti Massimo, Ioverno Antonella, Maloberti Alessandro, Fucile Ilaria, Cipollini Franco, Nesti Nicola, Mancusi Costantino, Pende Aldo, Giannattasio Cristina, Muiesan Maria Lorenza, Milan Alberto
  
  Abstract
  
  Hypertensive urgencies (HU) and hypertensive emergencies (HE) are challenges for the Emergency Department (ED). A prospective multicentre study is ongoing to characterize patients with acute hypertensive disorders, prevalence of subclinical hypertension-mediated organ damage (HMOD), short- and long-term prognosis; this is a preliminary report. Patients admitted to the ED with symptomatic blood pressure (BP) ?180/110?mmHg were enrolled. They were managed by ED personnel according to their clinical presentations. Subsequently they underwent clinical evaluation and subclinical HMOD assessment at a Hypertension Centre within 72?h from enrolment. 122 patients were included in this report. Mean age was 60.7±13.9 years, 52.5% were females. 18 (14.8%) patients were diagnosed with HE, 108 (88.5%) with HU. There were no differences in gender, BMI, and cardiovascular comorbidities between groups. At ED discharge, 66.7% and 93.6% (p?=?0.003) of HE and HU patients, respectively, had BP?180/110?mmHg. After 72?h, 34.4% of patients resulted normotensive; 35.2%, 22.1%, and 8.2% had hypertension grade 1, 2, and 3, respectively. Patients with uncontrolled BP at office evaluation had higher vascular HMOD (49.1 vs. 25.9%, p?=?0.045). Cardiac (60 vs. 34%, p?=?0.049), renal (27.8 vs. 9.6%, p?=?0.010) and cerebral (100 vs. 21%, p?0.001) HMOD was more frequent in HE compared to HU group. HE showed greater cardiac, renal, and cerebral subclinical HMOD, compared to HU. 72-hours BP control is not associated with different HMOD, except for vascular HMOD; therefore, proper comprehensive examination after discharge from the ED could provide added value in cardiovascular risk stratification of such patients. One third of patients with acute blood pressure rise evaluated to the ED resulted normotensive at office evaluation (
  © 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.
  
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• Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: A single country, multicenter, observational study (AT-TARGET-IT).
  Atherosclerosis

  2023 Feb;366():32-39. doi: 10.1016/j.atherosclerosis.2023.01.001.
  
  Gargiulo Paola, Basile Christian, Cesaro Arturo, Marzano Federica, Buonocore Davide, Asile Gaetano, Abbate Vincenza, Vicidomini Francesca, Paolillo Stefania, Spaccarotella Carmen Anna Maria, Catalano Angelo, Spirito Giulio, Merlini Piera Angelica, Maloberti Alessandro, Iannuzzo Gabriella, Ciccone Marco Matteo, Zito Anna Paola, Paloscia Leonardo, D'Alleva Alberto, Varbella Ferdinando, Corleto Antonella, Brunetti Natale Daniele, Corbo Maria Delia, Calabrò Paolo, Indolfi Ciro, Perrone-Filardi Pasquale
  
  Abstract
  
  BACKGROUND AND AIMS:
  Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice.
  
  METHODS:
  All data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study.
  
  RESULTS:
  798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab.
  
  CONCLUSIONS:
  PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.
  
  Copyright © 2023 Elsevier B.V. All rights reserved.
  
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• Hyperuricemia increases the risk of cardiovascular mortality associated with very high HdL-cholesterol level.
  Nutr Metab Cardiovasc Dis

  2023 Feb;33(2):323-330. doi: 10.1016/j.numecd.2022.11.024.
  
  Palatini Paolo, Virdis Agostino, Masi Stefano, Mengozzi Alessandro, Casiglia Edoardo, Tikhonoff Valerie, Cicero Arrigo F G, Ungar Andrea, Parati Gianfranco, Rivasi Giulia, Salvetti Massimo, Barbagallo Carlo M, Bombelli Michele, Dell'Oro Raffaella, Bruno Berardino, Lippa Luciano, D'Elia Lanfranco, Masulli Maria, Verdecchia Paolo, Reboldi Gianpaolo, Angeli Fabio, Mallamaci Francesca, Cirillo Massimo, Rattazzi Marcello, Cirillo Pietro, Gesualdo Loreto, Mazza Alberto, Giannattasio Cristina, Maloberti Alessandro, Volpe Massimo, Tocci Giuliano, Iaccarino Guido, Nazzaro Pietro, Galletti Ferruccio, Ferri Claudio, Desideri Giovambattista, Viazzi Francesca, Pontremoli Roberto, Muiesan Maria Lorenza, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  BACKGROUND AND AIMS:
  Whether the association between very high HDL-cholesterol levels and cardiovascular mortality (CVM) is modulated by some facilitating factors is unclear. Aim of the study was to investigate whether the risk of CVM associated with very high HDL-cholesterol is increased in subjects with hyperuricemia.
  
  METHODS AND RESULTS:
  Multivariable Cox analyses were made in 18,072 participants from the multicentre URRAH study stratified by sex and HDL-cholesterol category. During a median follow-up of 11.4 years there were 1307 cases of CVM. In multivariable Cox models a J-shaped association was found in the whole population, with the highest risk being present in the high HDL-cholesterol group [>80 mg/dL, adjusted hazard ratio (HR), 1.28; 95%CI, 1.02-1.61; p = 0.031)]. However, a sex-specific analysis revealed that this association was present only in women (HR, 1.34; 95%CI, 1.02-1.77; p = 0.034) but not in men. The risk of CVM related to high HDL-cholesterol was much greater in the women with high uric acid (>0.30 mmol/L, HR 1.61; 95%CI, 1.08-2.39) than in those with low uric acid (HR, 1.17; 95%CI, 0.80-1.72, p for interaction = 0.016). In women older than 70 years with hyperuricemia the risk related to high HDL-cholesterol was 1.83 (95%CI, 1.19-2.80, p 
  CONCLUSION:
  Our data indicate that very high HDL-cholesterol levels in women are associated with CVM in a J-shaped fashion. The risk of CVM is increased by concomitant hyperuricemia suggesting that a proinflammatory/oxidative state can enhance the detrimental cardiovascular effects associated with high HDL-cholesterol.
  
  Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• Lipoprotein(a): Cardiovascular Disease, Aortic Stenosis and New Therapeutic Option.
  Int J Mol Sci

  2022 Dec;24(1):. doi: 170.
  
  Maloberti Alessandro, Fabbri Saverio, Colombo Valentina, Gualini Elena, Monticelli Massimiliano, Daus Francesca, Busti Andrea, Galasso Michele, De Censi Lorenzo, Algeri Michela, Merlini Piera Angelica, Giannattasio Cristina
  
  Abstract
  
  Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)-Lp(a)-lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years.
  
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• Uric acid relationships with lipid profile and adiposity indices: Impact of different hyperuricemic thresholds.
  J Clin Hypertens (Greenwich)

  2023 Jan;25(1):78-85. doi: 10.1111/jch.14613.
  
  Maloberti Alessandro, Vanoli Jennifer, Finotto Alessandra, Bombelli Michele, Facchetti Rita, Redon Pau, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  Previous studies focused on the relationships between Serum Uric Acid (SUA) and lipids have found an association mainly with triglycerides. Furthermore, previous studies on adiposity indices have been focused on the evaluation of the Visceral Adiposity Index (VAI). The present study was aimed at providing within the same population a systematic evaluation of lipids and adiposity indices with SUA, employing both the classic cutoff for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study. We analyzed data collected in 1892 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA, lipid profile and variables necessary to calculate VAI, Cardio-Metabolic Index (CMI) and Lipid Accumulation Product (LAP). At linear regression model (corrected for confounders) SUA correlated with all the lipids values (with the strongest ? for triglycerides) and adiposity indices. When the two different cutoffs were compared, the URRAH one was significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non-HDL, P 
  © 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.
  
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• Serum uric acid / serum creatinine ratio as a predictor of cardiovascular events. Detection of prognostic cardiovascular cut-off values.
  J Hypertens

  2023 Jan;41(1):180-186. doi: 10.1097/HJH.0000000000003319.
  
  Casiglia Edoardo, Tikhonoff Valérie, Virdis Agostino, Grassi Guido, Angeli Fabio, Barbagallo Carlo M, Bombelli Michele, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Dell'Oro Raffaella, D'elia Lanfranco, Desideri Giovambattista, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Masi Stefano, Maloberti Alessandro, Masulli Maria, Mazza Alberto, Mengozzi Alessandro, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Salvetti Massimo, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Borghi Claudio,
  
  Abstract
  
  OBJECTIVE:
  In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the cut-off values of the ratio between serum uric acid (SUA) and serum creatinine (sCr) able to predict cardiovascular (CV) events.
  
  METHODS:
  Among 20 724 participants followed-up for 126 ± 64?months, after detecting cut-off by the receiver operating characteristic curves, we calculated by Cox models adjusted for confounders having CV events as dependent variable the hazard ratio (HR) of SUA/sCr > cut-off. We also verified if the role of cut-off varied with increasing SUA/sCr.
  
  RESULTS:
  A plausible prognostic cut-off of SUA/sCr was found and was the same in the whole database, in men and in women (>5.35). The HR of SUA/sCr > cut-off was 1.159 (95% confidence interval [CI] 1.092-1.131, P?0.03) in all, 1.161 (95% CI 1.021-1.335, P?0.02) in men, and 1.444 (95% CI 1.012-1.113, P?0.03) in women. In increasing quintiles of SUA/sCr the cut-offs were >3.08, >4.87, >5.35, >6.22 and >7.58, respectively. The HRs significantly increased from the 3rd to the 5th quintile (1.21, 95% CI 1.032-1.467, P?=?0.018; 1.294, 95% CI 1.101-1.521, P?=?0.002; and 1.642, 95% CI 1.405-1.919, P?0.0001; respectively), that is, over 5.35, whereas the 2nd quintile was not significantly different from the 1st (reference).
  
  CONCLUSION:
  Having SUA/sCr >5.35 is an independent CV risk indicator both in men and women. The cut-off is dynamic and significantly increases with increasing SUA/sCr.
  
  Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
  
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• Accuracy of home blood pressure measurement: the ACCURAPRESS study - a proposal of Young Investigator Group of the Italian Hypertension Society (Società Italiana dell'Ipertensione Arteriosa).
  Blood Press

  2022 Dec;31(1):297-304. doi: 10.1080/08037051.2022.2137461.
  
  Mancusi Costantino, Bisogni Valeria, Maloberti Alessandro, Manzi Maria Virginia, Visco Valeria, Biolcati Marco, Giani Valentina, Spannella Francesco, Monticone Silvia, Saladini Francesca, Rivasi Giulia, Turrin Giada, Pucci Giacomo, Pengo Martino, Bertacchini Fabio, Ferri Claudio, Grassi Guido, Muiesan Maria Lorenza, ,
  
  Abstract
  
  PURPOSE:
  Home blood pressure monitoring (HBPM) might be considered a valid alternative to ambulatory blood pressure monitoring (ABPM) for both the diagnosis and management of hypertension. Correct information on how to perform HBPM are crucial for its reliability. The aim of the present survey was to assess if hypertensive patients followed current recommendation on how to correctly perform HBPM measurements.
  
  MATERIALS AND METHODS:
  The survey included 30 different items on how to perform the HBPM. It was developed by the 'Young Investigators' group of the Italian Society of Arterial Hypertension (SIIA) and it was administered during the office visit between May 2019 and December 2021.
  
  RESULTS:
  A total of 643 hypertensive patients participated in the study. Main results show that, despite the rate of informed patients was relatively high (71% of the whole population), unacceptable number of patients did not follow indications on how to perform a correct HBPM. Patients who were informed on how to measure home BP had a significantly higher rate of correct position during measurement (78 vs. 22%, ?0.01), avoidance of talking and moving during measurement (68 vs. 32%, ?0.0001), and correct number and time interval between two measurements (85 vs. 15%, ?0.001). More accurate measurements of home BP were associated with less prevalence of carotid plaque.
  
  CONCLUSIONS:
  Correct performance for HBPM is low among patients treated in Italian hypertension centers. These findings shed light on the importance of correct HBPM measurements for the detection of accurate BP values for the proper management of hypertensive patients.
  
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• CMV seroprevalence and coronary CMV-DNA detection in immunocompetent patients with heart diseases.
  Minerva Med

  2023 Jun;114(3):289-299. doi: 10.23736/S0026-4806.22.07778-3.
  
  Cento Valeria, Colagrossi Luna, Bossi Irene, Armenia Daniele, Nava Alice, Piccinelli Enrico, Maloberti Alessandro, Inglese Elvira, Matarazzo Elisa, DI Ruscio Federica, Paba Pierpaolo, Marcuccilli Fabbio, Perrone Marco, Chiricolo Gaetano, Alteri Claudia, Scaglione Francesco, Vismara Chiara, Campisi Daniela A, Fanti Diana, Romeo Francesco, Andreoni Massimo, Oliva Fabrizio, Ceccherini-Silberstein Francesca, Giannattasio Cristina, Perno Carlo F
  
  Abstract
  
  BACKGROUND:
  Acute coronary syndromes (ACS) are a major cause of morbidity and mortality. As cytomegalovirus (CMV) may contribute to cardio-vascular (CV) manifestations, we sought to provide a proof-of-concept for the involvement of coronary and/or systemic CMV-reactivation as a possible ACS trigger.
  
  METHODS:
  We prospectively enrolled consecutive patients undergoing a coronary angiography for ACS (acute-cases, N.=136), or non-ACS reasons (chronic-cases, N.=57). Matched coronary and peripheral blood-samples were processed for quantification of CMV-DNAemia (RT-PCR), CMV-IgG/IgM, and CMV-IgG avidity (ELISA). Peripheral-blood samples from 17 healthy subjects were included as controls.
  
  RESULTS:
  Out of the 193 cases included, 18.1% were aged ?55 years, 92.5% were Central-European, and 100% immunocompetent. CMV-IgG seroprevalence was 91.7% (95%CI: 87.8-95.6), significantly higher than in healthy-controls (52.9% [95%CI: 29.2-76.5]; P
  CONCLUSIONS:
  CMV-IgG seroprevalence was high in patients with heart diseases. CMV-DNAemia can be found, although uncommonly, in coronary circulation during an ACS, with increased prevalence in older subjects and in absence of CV risk-factors, identifying possible areas for novel interventions.
  
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• Endothelial Dysfunction in Patients with Advanced Heart Failure Treated with Levosimendan Periodic Infusion Compared with Optimal Medical Therapy: A Pilot Study.
  Life (Basel)

  2022 Aug;12(9):. doi: 1322.
  
  Maloberti Alessandro, Sun Jinwei, Zannoni Jessica, Occhi Lucia, Bassi Ilaria, Fabbri Saverio, Colombo Valentina, Gualini Elena, Algeri Michela, Varrenti Marisa, Masciocco Gabriella, Perna Enrico, Oliva Fabrizio, Cipriani Manlio, Frigerio Maria, Giannattasio Cristina
  
  Abstract
  
  Endothelial dysfunction (ED) is frequently found in patients with heart failure (HF). Among several pharmacological agents reported to improve endothelial function, levosimendan seems to be a promising one, even though, to date, only two previously published studies have evaluated its effects on ED in these patients. The aim of our pilot study was to further investigate the role of periodic levosimendan infusion on endothelial function in patients affected by advanced HF. In this cross-sectional study, three different groups were enrolled: 20 patients with advanced HF treated with periodic levosimendan (LEVO), 20 patients with HF on optimal medical therapy (OMT), and 20 healthy subjects (control group). ED was evaluated through flow-mediated dilation (FMD) at the level of the brachial artery. The three groups presented similar ages with significant differences in gender distribution, systolic blood pressure, and chronic kidney disease (eGFR
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• [Long COVID: nosographic aspects and clinical epidemiology].
  G Ital Cardiol (Rome)

  2022 Sep;23(9):651-662. doi: 10.1714/3860.38447.
  
  Abrignani Maurizio G, Maloberti Alessandro, Temporelli Pier Luigi, Binaghi Giulio, Cesaro Arturo, Ciccirillo Francesco, Oliva Fabrizio, Gabrielli Domenico, Riccio Carmine, Gulizia Michele Massimo, Colivicchi Furio
  
  Abstract
  
  Recent evidence shows that a range of persistent or new symptoms can manifest after 4-12 weeks in a subset of patients who have recovered from acute SARS-CoV-2 infection, and this condition has been coined long COVID by COVID-19 survivors among social support groups. Long COVID can affect the whole spectrum of people with COVID-19, from those with very mild acute disease to the most severe forms. Like the acute form, long COVID has multisystemic aspects. Patients can manifest with a very heterogeneous multitude of symptoms, including fatigue, post-exertional malaise, dyspnea, cognitive impairment, sleep disturbances, anxiety and depression, muscle pain, brain fog, anosmia/dysgeusia, headache, and limitation of functional capacity, which impact their quality of life. Because of the extreme clinical heterogeneity, and also due to the lack of a shared, specific definition, it is very difficult to know the real prevalence and incidence of this condition. Risk factors for developing long COVID would be female sex, initial severity, and comorbidities. Globally, with the re-emergence of new waves, the population of people infected with SARS-CoV-2 continues to expand rapidly, necessitating a more thorough understanding of potential sequelae of COVID-19. This review summarizes up to date definitions and epidemiological aspects of long COVID.
  
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• Incident Atrial Fibrillation and In-Hospital Mortality in SARS-CoV-2 Patients.
  Biomedicines

  2022 Aug;10(8):. doi: 1940.
  
  Maloberti Alessandro, Giannattasio Cristina, Rebora Paola, Occhino Giuseppe, Ughi Nicola, Biolcati Marco, Gualini Elena, Rizzi Jacopo Giulio, Algeri Michela, Giani Valentina, Rossetti Claudio, Epis Oscar Massimiliano, Molon Giulio, Beltrame Anna, Bonfanti Paolo, Valsecchi Maria Grazia, Genovesi Simonetta
  
  Abstract
  
  (1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p
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• Negative prognostic impact of electrolyte disorders in patients hospitalized for Covid-19 in a large multicenter study.
  J Nephrol

  2023 Apr;36(3):621-626. doi: 10.1007/s40620-022-01429-3.
  
  Genovesi Simonetta, Regolisti Giuseppe, Rebora Paola, Occhino Giuseppe, Belli Michele, Molon Giulio, Citerio Giuseppe, Beltrame Anna, Maloberti Alessandro, Generali Elena, Giannattasio Cristina, Epis Oscar Massimiliano, Rossetti Claudio, Bellelli Giuseppe, De Nalda Ana Lleo, Capua Ilaria, Valsecchi Maria Grazia
  
  Abstract
  
  BACKGROUND:
  The prognostic impact of electrolyte disorders in hospitalized COVID-19 patients is unclear.
  
  METHODS:
  The study included all adult patients hospitalized for COVID-19 in four hospitals in Northern Italy between January 2020 and May 2021 with at least one serum potassium and sodium measurement performed within 3 days since admission. Primary outcome was in-hospital death; secondary outcome was Intensive Care Unit (ICU) admission. A cause-specific Cox proportional-hazards regression model was used for investigating the association between potassium and sodium (as either categorical or continuous variables) and mortality or admission to ICU.
  
  RESULTS:
  Analyses included 3,418 adult hospitalized COVID-19 patients. At multivariable analysis, both hyperkalemia (Hazard Ratio, [HR] 1.833, 95% Confidence Interval [CI] 1.371-2.450) and sK above the median (K 5.1 vs 4.1 mmol/L: HR 1.523, 95% CI 1.295-1.798), and hypernatremia (HR 2.313, 95%CI 1.772-3.018) and sNa above the median (Na 149 vs 139 mmol/L: HR 1.442, 95% CI 1.234-1.686), were associated with in-hospital death, whereas hypokalemia and hyponatremia were not. Hyponatremia was associated with increased hazard of ICU admission (HR 1.884, 95%CI 1.389-2.556).
  
  CONCLUSIONS:
  Electrolyte disorders detected at hospital admission may allow early identification of COVID-19 patients at increased risk of adverse outcomes.
  
  © 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.
  
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• Acupuncture in Arterial Hypertension: Evaluation of its Efficacy with Both Office and Ambulatory Blood Pressure Measurements.
  High Blood Press Cardiovasc Prev

  2022 Sep;29(5):429-434. doi: 10.1007/s40292-022-00530-9.
  
  Migliarese Cristina, Maloberti Alessandro, Gatto Roberto, Algeri Michela, Scarpellini Sara, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  A possible alternative to pharmacological antihypertensive therapies in grade 1 low risk hypertensive patients or in those experienced drugs adverse effects could be acupuncture.
  
  AIM:
  we focused on its possible effects on BP both as Office BP (OBP) and as Ambulatory BP Monitoring (ABPM) evaluating it before starting a 6 weeks twice weekly (total 12 session) acupuncture cycle and after 2 months from its completion.
  
  METHODS:
  in this prospective study we treated with acupuncture 45 patients: 24 of them presents high-normal BP values and low cardiovascular risk while 21 patients were on anti-hypertensive drug with slightly uncontrolled BP values (from 140 to 145 mmHg for Systolic BP-SBP-and/or from 90 to 95 mmHg for Diastolic BP-DBP).
  
  RESULTS:
  regarding SBP, a significant reduction have been observed for office values (from 134.2?±?15.7 to 125.1?±?12.2, p?=?0.03), and for ABPM 24 h (from 131.1?±?10.7 to 126.0?±?10.1, p?=?0.01) and day-time values (from 134.7?±?10.5 to 127.1?±?18.4, p?=?0.02). For DBP, only ABPM 24 h and day-time values showed significant changes (from 85.3?±?9.1 to 82.1?±?7.5, p?=?0.03; and from 88.5?±?9.3 to 85.7?±?7.8, p?=?0.02). Within session SBP decrease was -?5.8 mmHg (-3.75%) during the first session while it falls to - 2.1 mmHg (- 1.25%) and stands firmly under 2 mmHg for all the next session. At the last session SBP reduction was -?1.9 mmHg (- 1.6%).
  
  CONCLUSIONS:
  we found a significant reduction in office, 24 h and day-time ABPM SBP determined by a 6-weeks twice weekly acupuncture cycle that lasts at least for the first two months after its completion.
  
  © 2022. The Author(s).
  
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• Differences in Diagnosis and Management of Hypertensive Urgencies and Emergencies According to Italian Doctors from Different Departments Who Deal With Acute Increase in Blood Pressure-Data from Gear (Gestione Dell'emergenza e Urgenza in ARea Critica) Study.
  J Clin Med

  2022 May;11(11):. doi: 2986.
  
  Saladini Francesca, Mancusi Costantino, Bertacchini Fabio, Spannella Francesco, Maloberti Alessandro, Giavarini Alessandra, Rosticci Martina, Bruno Rosa Maria, Pucci Giacomo, Grassi Davide, Pengo Martino, Muiesan Maria Lorenza
  
  Abstract
  
  Background: Diagnosis and treatment of hypertension emergency (HE) and urgency (HU) may vary according to the physicians involved and the setting of the treatment. The aim of this study was to investigate differences in management of HE and HU according to the work setting of the physicians. Methods: The young investigators of the Italian Society of Hypertension developed a 23-item questionnaire spread by email invitation to the members of Italian Scientific societies involved in the field of emergency medicine and hypertension. Results: Six-hundred and sixty-five questionnaires were collected. No differences emerged for the correct definitions of HE and HU or for the investigation of possible drugs that may be responsible for an acute increase in BP. The techniques used to assess BP values (p
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• Sense of Coherence Predicts Physical Activity Maintenance and Health-Related Quality of Life: A 3-Year Longitudinal Study on Cardiovascular Patients.
  Int J Environ Res Public Health

  2022 Apr;19(8):. doi: 4700.
  
  Adorni Roberta, Greco Andrea, D'Addario Marco, Zanatta Francesco, Fattirolli Francesco, Franzelli Cristina, Maloberti Alessandro, Giannattasio Cristina, Steca Patrizia
  
  Abstract
  
  Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. A physically active lifestyle can improve the health-related quality of life (HRQoL) of people with CVD. Nevertheless, adherence to a physically active lifestyle is poor. This study examined the longitudinal (pre-event, 6-, 12-, 24-, and 36-month follow-ups) physical activity profiles in 275 patients (mean age = 57.1 years; SD = 7.87; 84% men) after the first acute coronary event. Moreover, it investigated the associations among physical activity, sense of coherence (SOC), and HRQoL. Physical activity profiles were identified through latent class growth analysis, and linear regressions were then performed to explore the association between physical activity, SOC, and HRQoL. After the cardiovascular event, 62% of patients reached adequate physical activity levels and maintained them over time (virtuous profile). The remaining 38% could not implement (23%) or maintain (15%) a healthy behavior. A strong SOC at baseline (standardized ? = 0.19, p = 0.002) predicted the probability of belonging to the virtuous profile. Moreover, a strong SOC at baseline (standardized ? = 0.27, p
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• Biochemical but not imaging parameters are predictive of outcome in septic shock: a pilot study.
  Cardiovasc Ultrasound

  2022 Mar;20(1):6. doi: 6.
  
  Belli Oriana E, Campolo Jonica, Vallerio Paola, Musca Francesco, Moreo Antonella, Maloberti Alessandro, Parolini Marina, Bonacchini Luca, Monti Gianpaola, De Gasperi Andrea, Fumagalli Roberto, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  Septic shock is a severe form of sepsis marked by hypotension with an ominous outcome despite the introduction of modern intensive care. The aim of the present study is to obtain a panel with biomarkers, echocardiographic and vascular parameters to better risk stratify patients and identify those at higher risk of ominous outcome.
  
  METHODS:
  Between May 2013 and April 2016, 35 consecutive patients admitted at the Intensive Care Unit (ICU) of ASST Great Metropolitan Hospital Niguarda with the diagnosis of severe sepsis or septic shock were enrolled. All patients underwent rest echocardiography and several circulating biomarkers of myocardial damage or oxidative stress.
  
  RESULTS:
  The multivariate Cox's proportional hazard model showed that the only independent prognostic predictor for 30-day mortality was the angiopoietin-2, (HR 1.017, 95% CI 1.000-1.034; P?=?0.049). An angiopoietin-2 concentrations ? of 33,418?pg/mL was identified as the optimal threshold for the discrimination between survivors and non survivors at the time of admission in ICU, with a sensitivity of 80% and a specificity of 68%.
  
  CONCLUSIONS:
  Septic shock has a poor in-hospital outcome even when the best of care is implemented. Among the biochemical parameters angiopoietin was able to identify patients at risk of death. The lowest the value at admission, the highest the risk of in-hospital death. No echocardiographic nor vascular parameter was able to predict outcome in this setting.
  
  © 2022. The Author(s).
  
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• Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project.
  Nutr Metab Cardiovasc Dis

  2022 May;32(5):1245-1252. doi: 10.1016/j.numecd.2022.01.028.
  
  Masulli Maria, D'Elia Lanfranco, Angeli Fabio, Barbagallo Carlo M, Bilancio Giancarlo, Bombelli Michele, Bruno Berardino, Casiglia Edoardo, Cianci Rosario, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Dell'Oro Raffaella, Desideri Giovambattista, Ferri Claudio, Gesualdo Loreto, Giannattasio Cristina, Grassi Guido, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Maloberti Alessandro, Masi Stefano, Mazza Alberto, Mengozzi Alessandro, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Reboldi Gianpaolo, Rivasi Giulia, Salvetti Massimo, Tikhonoff Valerie, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Virdis Agostino, Volpe Massimo, Borghi Claudio, Galletti Ferruccio,
  
  Abstract
  
  BACKGROUND AND AIM:
  The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes.
  
  METHODS AND RESULTS:
  The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ?5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-1.47) and CV mortality (HR:1.31, 95%CI:1.03-1.66), than those with SUA
  CONCLUSIONS:
  SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.
  
  Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• Uric acid associated with acute heart failure presentation in Acute Coronary Syndrome patients.
  Eur J Intern Med

  2022 May;99():30-37. doi: 10.1016/j.ejim.2022.01.018.
  
  Rebora Paola, Centola Marco, Morici Nuccia, Sacco Alice, Occhino Giuseppe, Viola Giovanna, Oreglia Jacopo, Castini Diego, Persampieri Simone, Sabatelli Ludovico, Ferrante Giulia, Lucreziotti Stefano, Carugo Stefano, Valsecchi Maria Grazia, Oliva Fabrizio, Giannattasio Cristina, Maloberti Alessandro
  
  Abstract
  
  We focused on the role of Uric Acid (UA) as a possible determinant of Heart Failure (HF) related issues in Acute Coronary Syndromes (ACS) patients. Main outcomes were acute HF and cardiogenic shock at admission, secondary outcomes were the use of Non Invasive Ventilation (NIV) and the admission Left Ventricular Ejection Fraction (LVEF). We consecutively enrolled 1269 ACS patients admitted to the cardiological Intensive Care Unit of the Niguarda and San Paolo hospitals (Milan, Italy) from June 2016 to June 2019. Median age was 68 (first-third quartile 59-77) years and males were 970 (76%). All the evaluated outcomes occurred more frequently in the hyperuricemic subjects (UA higher than 6 mg/dL for females and 7 mg/dL for males, n = 292): acute HF 35.8 vs 11.1% (p 
  Copyright © 2022. Published by Elsevier B.V.
  
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• Trends in all-cause mortality of hospitalized patients due to SARS-CoV-2 infection from a monocentric cohort in Milan (Lombardy, Italy).
  Z Gesundh Wiss

  2022 ;30(8):1985-1993. doi: 10.1007/s10389-021-01675-y.
  
  Ughi Nicola, Bernasconi Davide Paolo, Del Gaudio Francesca, Dicuonzo Armanda, Maloberti Alessandro, Giannattasio Cristina, Tarsia Paolo, Puoti Massimo, Scaglione Francesco, Beltrami Laura, Colombo Fabrizio, Bertuzzi Michaela, Bellone Andrea, Adinolfi Antonella, Valsecchi Maria Grazia, Epis Oscar Massimiliano, Rossetti Claudio,
  
  Abstract
  
  BACKGROUND:
  Robust data on case fatality rate (CFR) among inpatients with COVID-19 are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. This study quantified the overall CFR and described its trend in a cohort of hospitalized patients with SARS-CoV-2 in Italy. Admission to ICU, death, or discharge were the secondary outcomes.
  
  METHODS:
  This retrospective study is based on administrative health data and electronic case records of inpatients consecutively admitted to Niguarda Hospital between 21 February and 8 November 2020.
  
  RESULTS:
  An overall CFR of 18% was observed. CFR was significantly reduced during the second wave of contagion (1 June to 30 September, 16%) compared with the first wave (21 February to 31 May, 21%  = 0.015). Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was associated with a high risk of mortality in both waves. The incidence of severe disease and the need for ICU admission were lower in the second wave.
  
  CONCLUSION:
  CFR in SARS-CoV-2 inpatients was demonstrated to decrease over time. This reduction may partly reflect the changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to plan an exit strategy in case of future outbreaks.
  
  KEY MESSAGES:
  Before the advent of anti-COVID-19 vaccines, a multi-wave pattern of contagion was observed, and this trend conditioned the inpatient case fatality rate (CFR), which varied over time accordingly to the waves of contagion.Only preliminary results on the in-hospital mortality trend are available, along with a partial analysis of its determinants. Consequently, robust data on CFR among inpatients with SARS-CoV-2 infection are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. This study shows that the in-hospital mortality in patients with SARS-CoV-2 infection decreases over time.Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was invariably associated with a high risk of mortality during the whole study period (21 February to 8 November 2020), but the incidence of severe disease and the need for ICU admission were lower in the second wave of contagions (1 October to 8 November 2020). This reduction may partly reflect the impact of changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to inform the response to future outbreaks and to plan exit strategy by prioritizing high-risk populations.
  
  SUPPLEMENTARY INFORMATION:
  The online version contains supplementary material available at 10.1007/s10389-021-01675-y.
  
  © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.
  
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• The association of uric acid with mortality modifies at old age: data from the uric acid right for heart health (URRAH) study.
  J Hypertens

  2022 Apr;40(4):704-711. doi: 10.1097/HJH.0000000000003068.
  
  Ungar Andrea, Rivasi Giulia, Di Bari Mauro, Virdis Agostino, Casiglia Edoardo, Masi Stefano, Mengozzi Alessandro, Barbagallo Carlo M, Bombelli Michele, Bruno Bernardino, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'elia Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Ciccarelli Michele, Lippa Luciano, Mallamaci Francesca, Maloberti Alessandro, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Salvetti Massimo, Tikhonoff Valérie, Tocci Giuliano, Cianci Rosario, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  OBJECTIVES:
  In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study.
  
  METHODS:
  Eight thousand URRAH participants aged 65+ were included in the analysis. The predictive role of SUA was assessed using Cox regression models stratified according to the cut-off age of 75. SUA was tested as continuous and categorical variable (age-specific quartiles). The prognostic threshold of SUA for mortality was analysed using receiver operating characteristic curves.
  
  RESULTS:
  Among participants aged 65-74, multivariate Cox regression analysis adjusted for CV risk factors and comorbidities identified an independent association of SUA with both all-cause mortality (hazard ratio [HR] 1.169, 95% confidence interval [CI] 1.107-1.235) and CV mortality (HR 1.146, 95% CI 1.064-1.235). The cut-off value of 4.8?mg/dl discriminated mortality status. In participants aged 75+, we observed a J-shaped relationship of SUA with all-cause and CV mortality, with risk increasing at extreme SUA levels.
  
  CONCLUSIONS:
  These results confirmed the predictive role of SUA for all-cause and CV mortality in older adults, while revealing considerable age-related differences. Mortality risk increased at higher SUA levels in participants aged 65-74, with a prognostic threshold of 4.8?mg/dl. The relationship between SUA and mortality was J-shaped in oldest participants. Large interventional studies are needed to clarify the benefits and possible risks of urate-lowering treatments in older adults.
  
  Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
  
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• Heart Rate in Patients with SARS-CoV-2 Infection: Prevalence of High Values at Discharge and Relationship with Disease Severity.
  J Clin Med

  2021 Nov;10(23):. doi: 5590.
  
  Maloberti Alessandro, Ughi Nicola, Bernasconi Davide Paolo, Rebora Paola, Cartella Iside, Grasso Enzo, Lenoci Deborah, Del Gaudio Francesca, Algeri Michela, Scarpellini Sara, Perna Enrico, Verde Alessandro, Santolamazza Caterina, Vicari Francesco, Frigerio Maria, Alberti Antonia, Valsecchi Maria Grazia, Rossetti Claudio, Epis Oscar Massimiliano, Giannattasio Cristina, On The Behalf Of The Niguarda Covid-Working Group
  
  Abstract
  
  The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = ? = 0.17 per bpm, 95% CI 0.11; 0.22,
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• Twenty-Four-Hour Central (Aortic) Systolic Blood Pressure: Reference Values and Dipping Patterns in Untreated Individuals.
  Hypertension

  2022 Jan;79(1):251-260. doi: 10.1161/HYPERTENSIONAHA.121.17765.
  
  Weber Thomas, Protogerou Athanase D, Agharazii Mohsen, Argyris Antonis, Aoun Bahous Sola, Banegas Jose R, Binder Ronald K, Blacher Jacques, Araujo Brandao Andréa, Cruz Juan J, Danninger Kathrin, Giannatasio Cristina, Graciani Auxiliadora, Hametner Bernhard, Jankowski Piotr, Li Yan, Maloberti Alessandro, Mayer Christopher C, McDonnell Barry J, McEniery Carmel M, Antonio Mota Gomes Marco, Machado Gomes Annelise, Lorenza Muiesan Maria, Nemcsik Janos, Paini Anna, Rodilla Enrique, Schutte Aletta E, Sfikakis Petros P, Terentes-Printzios Dimitrios, Vallée Alexandre, Vlachopoulos Charalambos, Ware Lisa, Wilkinson Ian, Zweiker Robert, Sharman James E, Wassertheurer Siegfried,
  
  Abstract
  
  Central (aortic) systolic blood pressure (cSBP) is the pressure seen by the heart, the brain, and the kidneys. If properly measured, cSBP is closer associated with hypertension-mediated organ damage and prognosis, as compared with brachial SBP (bSBP). We investigated 24-hour profiles of bSBP and cSBP, measured simultaneously using Mobilograph devices, in 2423 untreated adults (1275 women; age, 18-94 years), free from overt cardiovascular disease, aiming to develop reference values and to analyze daytime-nighttime variability. Central SBP was assessed, using brachial waveforms, calibrated with mean arterial pressure (MAP)/diastolic BP (cSBP), or bSBP/diastolic blood pressure (cSBP), and a validated transfer function, resulting in 144?509 valid brachial and 130?804 valid central measurements. Averaged 24-hour, daytime, and nighttime brachial BP across all individuals was 124/79, 126/81, and 116/72 mm?Hg, respectively. Averaged 24-hour, daytime, and nighttime values for cSBP were 128, 128, and 125 mm?Hg and 115, 117, and 107 mm?Hg for cSBP, respectively. We pragmatically propose as upper normal limit for 24-hour cSBP 135 mm?Hg and for 24-hour cSBP 120 mm?Hg. bSBP dipping (nighttime-daytime/daytime SBP) was -10.6 % in young participants and decreased with increasing age. Central SBP dipping was less pronounced (-8.7% in young participants). In contrast, cSBP dipping was completely absent in the youngest age group and less pronounced in all other participants. These data may serve for comparison in various diseases and have potential implications for refining hypertension diagnosis and management. The different dipping behavior of bSBP versus cSBP requires further investigation.
  
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• The Role of Uric Acid in Acute and Chronic Coronary Syndromes.
  J Clin Med

  2021 Oct;10(20):. doi: 4750.
  
  Maloberti Alessandro, Biolcati Marco, Ruzzenenti Giacomo, Giani Valentina, Leidi Filippo, Monticelli Massimiliano, Algeri Michela, Scarpellini Sara, Nava Stefano, Soriano Francesco, Oreglia Jacopo, Sacco Alice, Morici Nuccia, Oliva Fabrizio, Piani Federica, Borghi Claudio, Giannattasio Cristina
  
  Abstract
  
  Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA's relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.
  
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• Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project.
  Front Cardiovasc Med

  2021 ;8():713652. doi: 713652.
  
  Russo Elisa, Viazzi Francesca, Pontremoli Roberto, Barbagallo Carlo M, Bombelli Michele, Casiglia Edoardo, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'Elia Lanfranco, Dell'Oro Raffaella, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Leoncini Giovanna, Mallamaci Francesca, Maloberti Alessandro, Masi Stefano, Mengozzi Alessandro, Mazza Alberto, Muiesan Maria L, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Rattazzi Marcello, Rivasi Giulia, Salvetti Massimo, Tikhonoff Valérie, Tocci Giuliano, Quarti Trevano Fosca A L, Ungar Andrea, Verdecchia Paolo, Virdis Agostino, Volpe Massimo, Grassi Guido, Borghi Claudio
  
  Abstract
  
  Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality. We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality. After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and
  Copyright © 2021 Russo, Viazzi, Pontremoli, Barbagallo, Bombelli, Casiglia, Cicero, Cirillo, Cirillo, Desideri, D'Elia, Dell'Oro, Ferri, Galletti, Gesualdo, Giannattasio, Iaccarino, Leoncini, Mallamaci, Maloberti, Masi, Mengozzi, Mazza, Muiesan, Nazzaro, Palatini, Parati, Rattazzi, Rivasi, Salvetti, Tikhonoff, Tocci, Quarti Trevano, Ungar, Verdecchia, Virdis, Volpe, Grassi and Borghi.
  
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• Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study.
  J Hum Hypertens

  2022 Nov;36(11):976-982. doi: 10.1038/s41371-021-00613-5.
  
  Tikhonoff Valérie, Casiglia Edoardo, Spinella Paolo, Barbagallo Carlo M, Bombelli Michele, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'elia Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Mallamaci Francesca, Maloberti Alessandro, Masi Stefano, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Rivasi Giulia, Salvetti Massimo, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Virdis Agostino, Volpe Massimo, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7?±?61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79?mg/dL or >284.91?µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p?=?0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79?mg/dL is a valid prognostic cut-off value.
  
  © 2021. The Author(s), under exclusive licence to Springer Nature Limited.
  
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• Atrial Fibrillation and Clinical Outcomes in a Cohort of Hospitalized Patients with Sars-Cov-2 Infection and Chronic Kidney Disease.
  J Clin Med

  2021 Sep;10(18):. doi: 4108.
  
  Genovesi Simonetta, Rebora Paola, Occhino Giuseppe, Rossi Emanuela, Maloberti Alessandro, Belli Michele, Bonfanti Paolo, Giannattasio Cristina, Rossetti Claudio, Epis Oscar Massimiliano, Ughi Nicola, Valsecchi Maria Grazia
  
  Abstract
  
  The aim of the study was to investigate the role of chronic kidney disease (CKD) on in-hospital mortality and on incident atrial fibrillation (AF) in patients infected with SARS-CoV-2. The incidence of acute kidney injury (AKI) was also investigated. Multivariable regression models were used to assess the association between renal function groups (estimated Glomerular Filtration Rate, eGFR, >60 mL/min, 30-59 mL/min,
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• Determinants of Functional Improvement After Cardiac Rehabilitation in Acute Coronary Syndrome.
  High Blood Press Cardiovasc Prev

  2021 Nov;28(6):579-587. doi: 10.1007/s40292-021-00473-7.
  
  Bianchi Sofia, Maloberti Alessandro, Peretti Alessio, Garatti Laura, Palazzini Matteo, Occhi Lucia, Bassi Ilaria, Sioli Sabrina, Biolcati Marco, Giani Valentina, Monticelli Massimiliano, Leidi Filippo, Ruzzenenti Giacomo, Beretta Giovanna, Giannattasio Cristina, Riccobono Salvatore
  
  Abstract
  
  INTRODUCTION:
  Cardiac rehabilitation (CR) is an effective tool for secondary prevention after acute coronary syndrome (ACS).
  
  AIM:
  Aim of our study was to find the significant determinants of exercise capacity (evaluated with the six-minute walking test-6-MWT) and functional improvement in patients undergoing CR after an ACS.
  
  METHODS:
  The study group included 298 patients (mean age 61.6 ± 10.2 years; males 80.2%) who, after ACS, were enrolled in CR program at Niguarda Hospital in Milan from 2015 to 2018. For all patients, we collected anamnestic, clinical and instrumental cardiological data. All patients performed a 6-MWT at the beginning (6-MWT-1) and at the end (6-MWT-2) of CR program. ? meters were used to represent functional improvement.
  
  RESULTS:
  Multiple linear regression models were carried out for 6-MWT-1, 6-MWT-2, ? meters and % ? meters. Standardized regression coefficients showed that age (? = - 0.237; p
  CONCLUSIONS:
  Our data showed that functional improvement after CR in ACS patients is mainly related to non-cardiological variables. Instead it is related to intrinsic factors, both modifiable (BMI) and non-modifiable (age, sex).
  
  © 2021. The Author(s).
  
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• Prevalence of hypertension mediated organ damage in subjects with high-normal blood pressure without known hypertension as well as cardiovascular and kidney disease.
  J Hum Hypertens

  2022 Jul;36(7):610-616. doi: 10.1038/s41371-021-00604-6.
  
  Maloberti Alessandro, Rebora Paola, Occhino Giuseppe, Alloni Marta, Musca Francesco, Belli Oriana, Spano Francesca, Santambrogio Gloria Maria, Occhi Lucia, De Chiara Benedetta, Casadei Francesca, Moreo Antonella, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (
  © 2021. The Author(s), under exclusive licence to Springer Nature Limited.
  
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• Troponin elevation in COVID-19 patients: An important stratification biomarker with still some open questions.
  Int J Cardiol

  2021 Oct;341():107-109. doi: 10.1016/j.ijcard.2021.07.049.
  
  Maloberti Alessandro, Biolcati Marco, Giannattasio Cristina
  
  
  
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• Continuous flow left ventricular assist devices do not worsen endothelial function in subjects with chronic heart failure: a pilot study.
  ESC Heart Fail

  2021 Oct;8(5):3587-3593. doi: 10.1002/ehf2.13484.
  
  Cortese Francesca, Ciccone Marco Matteo, Gesualdo Michele, Iacoviello Massimo, Frigerio Maria, Cipriani Manlio, Giannattasio Cristina, Maloberti Alessandro, Giordano Paola
  
  Abstract
  
  AIMS:
  To evaluate endothelial function in subjects with left ventricular assist devices (LVADs), comparing them with subjects with chronic heart failure with reduced ejection fraction on the list for heart transplant (HT) and with HT patients with a normal systolic cardiac function to identify any differences.
  
  METHODS:
  We enrolled 28 subjects with LVAD, 55 subjects with HT, and 42 subjects with heart failure on the transplant list. The subjects underwent a general physical examination, assessment of laboratory blood parameters, and assessment of endothelial function through flow-mediated dilation (FMD) of brachial artery.
  
  RESULTS:
  The three groups were homogeneous as regards age, gender, smoke abuse, C-reactive protein (CRP) and FMD parameters (P = ns). In LVAD group percentage of FMD change showed an inverse correlation with CRP (rho: -0.5, P: 0.003), a well-known marker of inflammation and tissue damage.
  
  CONCLUSIONS:
  Continuous flow related to LVAD seems to not worsen endothelial function. Endothelial function was not affected by cardiovascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, and tobacco habit), by the functional status expressed by New York Heart Association class, by the left ventricular systolic function and by the presence or absence of ischaemic heart disease in all the populations analysed. CRP was the only factor able to influence percentage of FMD change in patient with LVAD, reinforcing the hypothesis that inflammation is the main determinant of endothelial function.
  
  © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
  
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• Covid and Cardiovascular Diseases: Direct and Indirect Damages and Future Perspective.
  High Blood Press Cardiovasc Prev

  2021 Sep;28(5):439-445. doi: 10.1007/s40292-021-00464-8.
  
  Ruzzenenti Giacomo, Maloberti Alessandro, Giani Valentina, Biolcati Marco, Leidi Filippo, Monticelli Massimiliano, Grasso Enzo, Cartella Iside, Palazzini Matteo, Garatti Laura, Ughi Nicola, Rossetti Claudio, Epis Oscar Massimiliano, Giannattasio Cristina,
  
  Abstract
  
  SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia.
  
  © 2021. The Author(s).
  
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• Low Awareness of Cardiovascular Risk Factor Among Patients Admitted in Cardiac Rehabilitation: New Data for Further Implementation of Cardiovascular Rehabilitation Program.
  High Blood Press Cardiovasc Prev

  2021 May;28(3):253-254. doi: 10.1007/s40292-021-00451-z.
  
  Maloberti Alessandro, Monticelli Massimiliano, Bassi Ilaria, Riccobono Salvatore, Giannattasio Cristina
  
  
  
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• Uric acid in chronic coronary syndromes: Relationship with coronary artery disease severity and left ventricular diastolic parameter.
  Nutr Metab Cardiovasc Dis

  2021 May;31(5):1501-1508. doi: 10.1016/j.numecd.2021.01.023.
  
  Maloberti Alessandro, Bossi Irene, Tassistro Elena, Rebora Paola, Racioppi Angelo, Nava Stefano, Soriano Francesco, Piccaluga Emanuela, Piccalò Giacomo, Oreglia Jacopo, Vallerio Paola, Pirola Roberto, De Chiara Benedetta, Oliva Fabrizio, Moreo Antonella, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND AIMS:
  Uric Acid (UA) has been related to the development of Cardio-Vascular (CV) events in patients affected by Chronic Coronary Syndromes (CCS). Among various hypothesis, two arise: UA may negatively act on coronary artery determining a higher degree of atherosclerotic disease, and/or on heart determining a higher prevalence of diastolic dysfunction. Both the above hypothesized effects are object of our investigation.
  
  METHODS AND RESULTS:
  231 patients who were admitted to the cardiological department of the Niguarda Hospital (Milan, Italy) for CCS from January 2017 to June 2018 were enrolled. Coronary atherosclerotic burden was evaluated from coronary angiography as the number and type of involved vessels, as well as with both Gensini and Syntax scores. All subjects underwent a complete echocardiogram. At unadjusted and adjusted/multivariable analysis, UA levels were not significantly associated with variables analysed from the coronary angiography (number and type of vessels involved, neither the Gensini and Syntax scores) as well as with echocardiographic parameters regarding systolic and diastolic function.
  
  CONCLUSIONS:
  In conclusion, the main finding of our work is the absence of a role for UA in determining coronary arteries disease as well as LV diastolic dysfunction in CCS subjects. Taking together the results of previous studies with ours, we hypothesize that UA could act on heart (both on coronary arteries and on LV function) in an early phase of the disease, whereas while in the advanced stages other factors (previous myocardial infarction, previous myocardial revascularization and so on) may overshadow its effects.
  
  Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• Ankle-Brachial Index Is a Predictor of In-Hospital Functional Status but Not of Complications in Hospitalized Elderly Patients.
  Gerontology

  2021 ;67(6):674-680. doi: 10.1159/000514450.
  
  Maloberti Alessandro, Fribbi Francesco, Motto Elena, Vallerio Paola, Occhi Lucia, Palazzini Matteo, Peretti Alessio, Ferraro Giovanni, Agrati Antonio, Colombo Fabrizio, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Atherosclerosis causes a chronic reduction of vascularization with consequent impairment of the performance of organs, like the brain or muscles, which determines the functional and cognitive decline of the elderly and their ability to respond to acute stressful condition. Therefore, our aim was to evaluate if ankle brachial index (ABI) could effectively be a determinant of in-hospital functional status and complications in elderly hospitalized patients.
  
  METHODS:
  This is a monocentric cross-sectional study of 189 patients aged 65 years or older. The study was undertaken at the Internal Medicine ward of Niguarda Hospital in Milan. ABI (BOSO ABY-System 100) and in-hospital status (activities of daily living, ADL and instrumental activities of daily living, IADL) were collected on the second day of hospitalization. Complications (falls and delirium episodes) were also recorded during the whole hospitalization period.
  
  RESULTS:
  The average age of patients was 79.3 ± 6.9 years. Among outcomes, only ADL (r = 0.192, p = 0.007) and IADL score (r = 0.200, p = 0.005) showed significant correlation with ABI. Moreover, during the subsequent logistic regression, ABI remained among the statistically significant determinants of both scores (? = 0.231, p = 0.013 and ? = 0.314, p = 0.001, respectively).
  
  CONCLUSIONS:
  The main result of our study is the finding of ABI as a significant determinant of acute in-hospital functional impairment (evaluated as ADL and IADL scores). The continuous exposure of the brain and muscles to the reduced perfusions induced by vascular atherosclerosis, probably determined the reduced ability to respond to stressful conditions.
  
  © 2021 S. Karger AG, Basel.
  
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• Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project.
  J Nephrol

  2022 Jan;35(1):211-221. doi: 10.1007/s40620-021-00985-4.
  
  Russo Elisa, Viazzi Francesca, Pontremoli Roberto, Barbagallo Carlo Maria, Bombelli Michele, Casiglia Edoardo, Cicero Arrigo Francesco Giuseppe, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'Elia Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Leoncini Giovanna, Mallamaci Francesca, Maloberti Alessandro, Masi Stefano, Mengozzi Alessandro, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Rattazzi Marcello, Rivasi Giulia, Salvetti Massimo, Tikhonoff Valérie, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Virdis Agostino, Volpe Massimo, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  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.
  
  © 2021. The Author(s).
  
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• Protein Intake and Physical Activity in Newly Diagnosed Patients with Acute Coronary Syndrome: A 5-Year Longitudinal Study.
  Nutrients

  2021 Feb;13(2):. doi: 634.
  
  Greco Andrea, Brugnera Agostino, Adorni Roberta, D'Addario Marco, Fattirolli Francesco, Franzelli Cristina, Giannattasio Cristina, Maloberti Alessandro, Zanatta Francesco, Steca Patrizia
  
  Abstract
  
  Cardiovascular disease is one of the most common causes of hospitalization and is associated with high morbidity and mortality rates. Among the most important modifiable and well-known risk factors are an unhealthy diet and sedentary lifestyle. Nevertheless, adherence to healthy lifestyle regimes is poor. The present study examined longitudinal trajectories (pre-event, 6-, 12-, 24-, 36-, and 60-month follow-ups) of protein intake (fish, legumes, red/processed meat) and physical activity in 275 newly-diagnosed patients with acute coronary syndrome. Hierarchical Generalized Linear Models were performed, controlling for demographic and clinical variables, the season in which each assessment was made, and the presence of anxiety and depressive symptoms. Significant changes in protein intake and physical activity were found from pre-event to the six-month follow-up, suggesting the adoption of healthier behaviors. However, soon after the six-month follow-up, patients experienced significant declines in their healthy behaviors. Both physical activity and red/processed meat intake were modulated by the season in which the assessments took place and by anxiety symptoms over time. The negative long-term trajectory of healthy behaviors suggests that tailored interventions are needed that sustain patients' capabilities to self-regulate their behaviors over time and consider patient preference in function of season.
  
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• The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk.
  Clin Res Cardiol

  2021 Jul;110(7):1073-1082. doi: 10.1007/s00392-021-01815-0.
  
  Pugliese Nicola Riccardo, Mengozzi Alessandro, Virdis Agostino, Casiglia Edoardo, Tikhonoff Valerie, Cicero Arrigo F G, Ungar Andrea, Rivasi Giulia, Salvetti Massimo, Barbagallo Carlo M, Bombelli Michele, Dell'Oro Raffaella, Bruno Berardino, Lippa Luciano, D'Elia Lanfranco, Verdecchia Paolo, Mallamaci Francesca, Cirillo Massimo, Rattazzi Marcello, Cirillo Pietro, Gesualdo Loreto, Mazza Alberto, Giannattasio Cristina, Maloberti Alessandro, Volpe Massimo, Tocci Giuliano, Georgiopoulos Georgios, Iaccarino Guido, Nazzaro Pietro, Parati Gianfranco, Palatini Paolo, Galletti Ferruccio, Ferri Claudio, Desideri Giovambattista, Viazzi Francesca, Pontremoli Roberto, Muiesan Maria Lorenza, Grassi Guido, Masi Stefano, Borghi Claudio,
  
  Abstract
  
  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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• High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid.
  Eur J Prev Cardiol

  2021 Feb;():. doi: zwab023.
  
  Palatini Paolo, Parati Gianfranco, Virdis Agostino, Reboldi Gianpaolo, Masi Stefano, Mengozzi Alessandro, Casiglia Edoardo, Tikhonoff Valerie, Cicero Arrigo F G, Ungar Andrea, Rivasi Giulia, Salvetti Massimo, Barbagallo Carlo M, Bombelli Michele, Dell'Oro Raffaella, Bruno Berardino, Lippa Luciano, D'Elia Lanfranco, Verdecchia Paolo, Angeli Fabio, Mallamaci Francesca, Cirillo Massimo, Rattazzi Marcello, Cirillo Pietro, Gesualdo Loreto, Mazza Alberto, Giannattasio Cristina, Maloberti Alessandro, Volpe Massimo, Tocci Giuliano, Georgiopoulos Georgios, Iaccarino Guido, Nazzaro Pietro, Galletti Ferruccio, Ferri Claudio, Desideri Giovambattista, Viazzi Francesca, Pontremoli Roberto, Muiesan Maria Lorenza, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  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.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
  
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• Effects of Environmental Factors on Severity and Mortality of COVID-19.
  Front Med (Lausanne)

  2020 ;7():607786. doi: 607786.
  
  Kifer Domagoj, Bugada Dario, Villar-Garcia Judit, Gudelj Ivan, Menni Cristina, Sudre Carole, Vu?kovi? Frano, Ugrina Ivo, Lorini Luca F, Posso Margarita, Bettinelli Silvia, Ughi Nicola, Maloberti Alessandro, Epis Oscar, Giannattasio Cristina, Rossetti Claudio, Kalogjera Livije, Per?ec Jasminka, Ollivere Luke, Ollivere Benjamin J, Yan Huadong, Cai Ting, Aithal Guruprasad P, Steves Claire J, Kantele Anu, Kajova Mikael, Vapalahti Olli, Sajantila Antti, Wojtowicz Rafal, Wierzba Waldemar, Krol Zbigniew, Zaczynski Artur, Zycinska Katarina, Postula Marek, Luk?i? Ivica, ?ivljak Rok, Markoti? Alemka, Brachmann Johannes, Markl Andreas, Mahnkopf Christian, Murray Benjamin, Ourselin Sebastien, Valdes Ana M, Horcajada Juan P, Castells Xavier, Pascual Julio, Allegri Massimo, Primorac Dragan, Spector Tim D, Barrios Clara, Lauc Gordan
  
  Abstract
  
  Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988,
  Copyright © 2021 Kifer, Bugada, Villar-Garcia, Gudelj, Menni, Sudre, Vu?kovi?, Ugrina, Lorini, Posso, Bettinelli, Ughi, Maloberti, Epis, Giannattasio, Rossetti, Kalogjera, Per?ec, Ollivere, Ollivere, Yan, Cai, Aithal, Steves, Kantele, Kajova, Vapalahti, Sajantila, Wojtowicz, Wierzba, Krol, Zaczynski, Zycinska, Postula, Luk?i?, ?ivljak, Markoti?, Brachmann, Markl, Mahnkopf, Murray, Ourselin, Valdes, Horcajada, Castells, Pascual, Allegri, Primorac, Spector, Barrios and Lauc.
  
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• Metabolic syndrome is related to vascular structural alterations but not to functional ones both in hypertensives and healthy subjects.
  Nutr Metab Cardiovasc Dis

  2021 Apr;31(4):1044-1052. doi: 10.1016/j.numecd.2020.11.011.
  
  Maloberti Alessandro, Bombelli Michele, Vallerio Paola, Milani Martina, Cartella Iside, Tavecchia Giovanni, Tognola Chiara, Grasso Enzo, Sun Jinwei, De Chiara Benedetta, Riccobono Salvatore, Grassi Guido, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND AIMS:
  Metabolic Syndrome (MS) has been related to an impairment in arterial structural and functional properties with heterogeneous results. In this paper we focused on the effects of MS on arterial carotid-femoral PWV and common carotid IMT in two different populations, one of hypertensive patients and one of healthy controls.
  
  METHODS AND RESULTS:
  We enrolled 816 consecutive HT and 536 healthy controls. Vascular structural (IMT) and functional (PWV) properties were evaluated. NCEP-ATP-III criteria were used for diagnosis of MS. MS was diagnosed in 26.9% and 6.9% in hypertensive and control subjects, respectively. PWV was similar in controls with and without MS (7.7 ± 1.9 vs 7.6 ± 1.1 m/s, p = 0.69), while IMT was higher in controls with than those without MS (0.64 ± 0.18 vs 0.57 ± 0.13 mm, p = 0.02). Hypertensives with MS were older (57.9 ± 12.2 vs 52.7 ± 14.1 years, p 
  CONCLUSIONS:
  the main finding of our work is that MS is a significant determinant of IMT while this is not the case for PWV. This result have been confirmed both in hypertensive subjects and in healthy controls.
  
  Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• 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. doi: 10.1097/HJH.0000000000002600.
  
  Maloberti Alessandro, Bombelli Michele, Facchetti Rita, Barbagallo Carlo Maria, Bernardino Bruno, Rosei Enrico Agabiti, Casiglia Edoardo, Cicero Arrigo Francesco Giuseppe, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'elia Lanfranco, Dell'Oro Raffaella, Ferri Claudio, Galletti Ferruccio, Giannattasio Cristina, Loreto Gesualdo, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Masi Stefano, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Parati Gianfranco, Palatini Paolo, Pauletto Paolo, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Rivasi Giulia, Salvetti Massimo, Tikhonoff Valerie, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Virdis Agostino, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  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.
  
  Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
  
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• Costs and effects of cardiovascular risk reclassification using the ankle-brachial index (ABI) in addition to the Framingham risk scoring in women.
  Atherosclerosis

  2021 Jan;317():59-66. doi: 10.1016/j.atherosclerosis.2020.11.004.
  
  Cortesi Paolo Angelo, Maloberti Alessandro, Micale Mariangela, Pagliarin Federica, Antonazzo Ippazio Cosimo, Mazzaglia Giampiero, Giannattasio Cristina, Mantovani Lorenzo Giovanni
  
  Abstract
  
  BACKGROUND AND AIMS:
  Ankle brachial index (ABI) is a simple and cheap parameter to assess the presence of atherosclerosis. It could also help correctly reclassify the cardiovascular risk when added to the Framingham risk score (FRS). Recent evidence has demonstrated improvement in prediction performance of ABI when added to FRS, particularly in women. However, no studies have been published yet evaluating the cost-effectiveness of this approach. This study attempts to fill in this gap by assessing the cost-effectiveness of ABI measurements in primary prevention in women.
  
  METHODS:
  We developed a Markov model to compare two different strategies for assessing the cardiovascular risk (low, intermediate and high) among women in the general population: 1) FRS strategy, and 2) FRS + ABI strategy; and the relative impact associated with interventions for preventing CV events in intermediate and high-risk categories.
  
  RESULTS:
  In the base-case analysis, FRS + ABI reported an additional cost of ? 110 and a gain of 0.0039 QALYs per patient, resulting in an ICER of ? 27.986/QALY, when compared to FRS alone. The ICER improved to ?1.641/QALY when using a lifetime horizon. The effectiveness of preventive CV disease interventions reported also a significant impact. A 32% reduction of CV events was the minimum value estimated to maintain FRS + ABI as a cost-effective strategy.
  
  CONCLUSIONS:
  The addition of ABI to FRS is a cost-effective approach in women classified at low and intermediate risk with FRS only. This new approach gives the possibility to reclassify and allocate them into the appropriate risk group and treatment.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Hyperuricemia prevalence in healthy subjects and its relationship with cardiovascular target organ damage.
  Nutr Metab Cardiovasc Dis

  2021 Jan;31(1):178-185. doi: 10.1016/j.numecd.2020.08.015.
  
  Maloberti Alessandro, Qualliu Esmerilda, Occhi Lucia, Sun Jinwei, Grasso Enzo, Tognola Chiara, Tavecchia Giovanni, Cartella Iside, Milani Martina, Vallerio Paola, Signorini Stefano, Brambilla Paolo, Casati Marco, Bombelli Michele, Grassi Guido, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND AIM:
  Heterogeneous results have been obtained in the relationship between Uric Acid (UA) and Target Organ Damage (TOD). In the present study we sought to assess the prevalence of hyperuricemia in healthy subjects as well as the role of UA in determining TOD. We evaluated vascular, cardiac and renal TODs in the whole population as well as sub-grouped by gender.
  
  METHODS AND RESULTS:
  As many as 379 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Mass Index (LVMI) and carotid Intima-Media Thickness (IMT). Hyperuricemia was defined with the classic cut-off (>7.0 in men and >6.0 mg/dL in women) but also with a most recently defined one (5.6 mg/dL for both sex). Hyperuricemia was present in 6.3% of the whole population (7.3% males, 2.8% females) considering the classic cut-off, while, with the recently identified one, it was present in 28.2% of the whole population (37.3% males, 4.7% females). Despite all the evaluated TODs significantly correlated with UA, linear multivariate regression analysis showed that none of them, except for GFR, displayed UA as a significant covariate. Similar figures were found also when both correlation and linear regression analyses were repeated in the two genders separately.
  
  CONCLUSIONS:
  Hyperuricemia is an important problem also in healthy subjects and its prevalence could further increase if lower cut-off will be used. In this specific population UA is significantly associated with renal impairment while this was not the case for cardiac and vascular damage.
  
  Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• Impact of admission serum acid uric levels on in-hospital outcomes in patients with acute coronary syndrome.
  Eur J Intern Med

  2020 Dec;82():62-67. doi: 10.1016/j.ejim.2020.07.013.
  
  Centola Marco, Maloberti Alessandro, Castini Diego, Persampieri Simone, Sabatelli Ludovico, Ferrante Giulia, Lucreziotti Stefano, Morici Nuccia, Sacco Alice, Oliva Fabrizio, Rebora Paola, Giannattasio Cristina, Mafrici Antonio, Carugo Stefano
  
  Abstract
  
  BACKGROUND:
  To assess the association between admission serum uric acid (SUA) levels and in-hospital outcomes in a real-world patients population with acute coronary syndrome (ACS) and to investigate the potential incremental prognostic value of SUA added to GRACE score (GRACE-SUA score).
  
  METHODS:
  The data of consecutive ACS patients admitted to Coronary Care Unit of San Paolo and Niguarda hospitals in Milan (Italy) were retrospectively analyzed.
  
  RESULTS:
  1088 patients (24% female) were enrolled. Mean age was 68 years (IQR 60-78). STEMI and NSTE-ACS patients were 504 (46%) and 584 (54%) respectively. SUA (OR 1.72 95%CI 1.33-2.22, p 
  CONCLUSIONS:
  High admission levels of SUA are independently associated with in-hospital adverse outcomes and mortality in a contemporary population of ACS patients. The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality in this study population.
  
  Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• 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. doi: 10.1097/HJH.0000000000002589.
  
  Muiesan Maria L, Salvetti Massimo, Virdis Agostino, Masi Stefano, Casiglia Edoardo, Tikhonoff Valérie, Barbagallo Carlo M, Bombelli Michele, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'Eliak Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Mallamaci Francesca, Maloberti Alessandro, Mazza Alberto, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Rattazzi Marcello, Rivasi Giulia, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  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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• Thoracic radiotherapy as a risk factor for heart ischemia in subjects treated with chest irradiation and chemotherapy and without classic cardiovascular RISK factors.
  Radiother Oncol

  2020 Nov;152():146-150. doi: 10.1016/j.radonc.2020.07.004.
  
  Vallerio Paola, Maloberti Alessandro, Palazzini Matteo, Occhi Lucia, Peretti Alessio, Nava Stefano, Soriano Francesco, Musca Francesco, De Chiara Benedetta, Belli Oriana, Moreo Antonella, Bisceglia Irma, Lestuzzi Chiara, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in increasing mortality rate in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of Coronary Artery Disease (CAD), a cardiological screening involving exercise stress electrocardiography after 5-10 years from radiotherapy is advised. We sought to determine the rate of ischemia at exercise stress electrocardiography in a population of patients without cardiovascular risk factors who sustained radiotherapy, using a cohort of patients presenting with at least one cardiovascular risk factor as control group.
  
  DESIGN AND METHODS:
  A population of 115 patients who sustained chest irradiation (and associated chemotherapy), presenting without classic cardiovascular risk factors or typical symptoms suggesting CAD, was evaluated with exercise stress electrocardiography. 135 patients with at least one risk factor for cardiovascular disease candidate to stress testing for primary prevention or for atypical symptoms served as control group.
  
  RESULTS:
  The cohort of irradiated patients without classical cardiovascular risk factors is younger (48.7 ± 10.1 vs 60.5 ± 10.8 years, p 
  CONCLUSIONS:
  Chest irradiation represents a strong cardiovascular risk factor. In fact, prevalence of positive ECG-stress test is not different (nor higher and nor lower) in irradiated subjects without cardiovascular risk and not irradiated patients with classic cardiovascular risk.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Functional Improvement After Outpatient Cardiac Rehabilitation in Acute Coronary Syndrome Patients is Not Related to Improvement in Left Ventricular Ejection Fraction.
  High Blood Press Cardiovasc Prev

  2020 Jun;27(3):225-230. doi: 10.1007/s40292-020-00374-1.
  
  Peretti A, Maloberti Alessandro, Garatti L, Palazzini M, Triglione N, Occhi L, Sioli S, Sun J W, Moreo A, Beretta G, Giannattasio C, Riccobono S
  
  Abstract
  
  INTRODUCTION:
  Cardiac rehabilitation (CR) improves the functional capacity and the prognosis of patients with coronary artery disease.
  
  AIM:
  Our study was aimed at assessing the relationship between functional improvement (evaluated with 6-min Walk Test-6MWT) and the improvement in left ventricular ejection fraction (LVEF) after CR.
  
  METHODS:
  We collected data from 249 patients (age 66.79?±?11.06 years; males 81.52%) with a recent history of Acute Coronary Syndrome that performed CR. The functional improvement after CR was expressed as the ? between distance covered at the final versus the initial 6-min Walking Test (6-MWT), while LVEF was calculated with transthoracic echocardiogram at the beginning and at the end of the CR.
  
  RESULTS:
  Patients were divided accordingly to their pre-rehab LVEF (??55% vs?55%). With superimposable age and baseline 6MWT distance covered (434.58 vs 405.12 m, p?=?0.08), the latter group presented higher ? meter values at 6MWT (167.93 vs 193.97 m, p?=?0.018). However, no statistically significant positive correlation between ? meters and ? LVEF was found. Moreover, linear regression analyses found that nor baseline LVEF nor ? LVEF were significant determinants of ? meters when considering the whole group, with age, basal 6MWT and peak CK-MB as additional covariates in the model.
  
  CONCLUSION:
  Although it could be expected that an increase in LVEF is related to the functional improvement after CR, no significant correlation was found in our population.
  
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• What hypertensive patients want to know [and from whom] about their disease: a two-year longitudinal study.
  BMC Public Health

  2020 Mar;20(1):308. doi: 308.
  
  Cappelletti Erika R, Greco Andrea, Maloberti Alessandro, Giannattasio Cristina, Steca Patrizia, D'Addario Marco
  
  Abstract
  
  BACKGROUND:
  This study explored both the evolution of the information needs and the perceived relevance of different health information sources in patients with essential hypertension. It also investigated the relationships between information needs and the perceived relevance of information sources with socio-demographic and clinical variables.
  
  METHODS:
  Two hundred and two patients with essential arterial hypertension were enrolled in the study and evaluated at baseline and during three follow-ups at 6, 12 and 24?months after baseline. Patients had a mean age of 54.3?years [range 21-78; SD?=?10.4], and 43% were women. Repeated measures ANOVA, Bonferroni post hoc tests, and Cochran's Q Test were performed to test differences in variables of interest over time.
  
  RESULTS:
  It was observed a significant reduction in all the domains of information needs related to disease management except for pharmacological treatment and risks and complications. At baseline, patients reported receiving health information primarily from specialists, general practitioners, relatives, and television, but the use of these sources decreased over time, even if the decrease was significant only for relatives. Multiple patterns of relationships were found between information needs and the perceived relevance of sources of information and socio-demographics and clinical variables, both at baseline and over time.
  
  CONCLUSIONS:
  The findings showed a general decrease in both the desire for information and the perceived relevance of different information sources. Hypertensive patients appeared to show little interest in health communication topics as their disease progressed. Understanding patients' information needs and the perceived relevance of different information sources is the first step in implementing tailored communication strategies that can promote patients' self-management skills and optimal clinical outcomes.
  
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• Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.
  High Blood Press Cardiovasc Prev

  2020 Apr;27(2):121-128. doi: 10.1007/s40292-020-00368-z.
  
  Maloberti Alessandro, Giannattasio C, Bombelli M, Desideri G, Cicero A F G, Muiesan M L, Rosei E A, Salvetti M, Ungar A, Rivasi G, Pontremoli R, Viazzi F, Facchetti R, Ferri C, Bernardino B, Galletti F, D'Elia L, Palatini P, Casiglia E, Tikhonoff V, Barbagallo C M, Verdecchia P, Masi S, Mallamaci F, Cirillo M, Rattazzi M, Pauletto P, Cirillo P, Gesualdo L, Mazza A, Volpe M, Tocci G, Iaccarino G, Nazzaro P, Lippa L, Parati G, Dell'Oro R, Quarti-Trevano F, Grassi G, Virdis A, Borghi C,
  
  Abstract
  
  The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (>?6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.
  
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• Association between uric acid and pulse wave velocity in hypertensive patients and in the general population: a systematic review and meta-analysis.
  Blood Press

  2020 Aug;29(4):220-231. doi: 10.1080/08037051.2020.1735929.
  
  Rebora Paola, Andreano Anita, Triglione Nicola, Piccinelli Enrico, Palazzini Matteo, Occhi Lucia, Grassi Guido, Valsecchi Maria Grazia, Giannattasio Cristina, Maloberti Alessandro
  
  Abstract
  
  The association between serum uric acid (SUA) and pulse wave velocity (PWV), has been extensively evaluated but with some discrepancies in results. A further limitation refers to the fact that only few data were analyzed taking into account the possible effects of gender. The purpose of this study was to estimate the association between SUA and arterial stiffness in general population and hypertensive patients, as a whole population and as divided by gender, by pooling results from existing studies. Carotid-femoral and brachial-ankle PWV (cf- and ba-PWV) have been analyzed separately and subgroup analyses by gender are reported. Among 692 potentially relevant works, 24 articles were analyzed. Seven studies referred to cf-PWV in the general population with an overall positive association at adjusted analysis for both males and females (beta regression coefficient (ß): 0.07; 95%CI: 0.03; 0.11 and ß: 0.06; 95%CI: 0.03; 0.09, respectively). Twelve studies referred to ba-PWV in the general population with the finding of a positive association at adjusted analysis for females (ß: 0.04; 95% confidence interval (CI): 0.01;0.07), but not for males (ß: 0.13; 95%CI: -0.09; 0.34). In hypertensive patients only four studies evaluated cf-PWV and one ba-PWV with only one study (with cf-PWV) finding positive association. The association between SUA and cf-PWV resulted significant in general population in both males and females while it was only significant for female regarding ba-PWV. Furthermore, the few available studies found no significant relationship between SUA and both cf- and ba-PWV in hypertensive subjects.
  
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• Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years.
  Hypertension

  2020 Feb;75(2):302-308. doi: 10.1161/HYPERTENSIONAHA.119.13643.
  
  Virdis Agostino, Masi Stefano, Casiglia Edoardo, Tikhonoff Valerie, Cicero Arrigo F G, Ungar Andrea, Rivasi Giulia, Salvetti Massimo, Barbagallo Carlo M, Bombelli Michele, Dell'Oro Raffaella, Bruno Berardino, Lippa Luciano, D'Elia Lanfranco, Verdecchia Paolo, Mallamaci Francesca, Cirillo Massimo, Rattazzi Marcello, Cirillo Pietro, Gesualdo Loreto, Mazza Alberto, Giannattasio Cristina, Maloberti Alessandro, Volpe Massimo, Tocci Giuliano, Georgiopoulos Georgios, Iaccarino Guido, Nazzaro Pietro, Parati Gianfranco, Palatini Paolo, Galletti Ferruccio, Ferri Claudio, Desideri Giovambattista, Viazzi Francesca, Pontremoli Roberto, Muiesan Maria Lorenza, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21-1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146-2.97];
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• Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.
  J Hypertens

  2020 Mar;38(3):412-419. doi: 10.1097/HJH.0000000000002287.
  
  Casiglia Edoardo, Tikhonoff Valérie, Virdis Agostino, Masi Stefano, Barbagallo Carlo M, Bombelli Michele, Bruno Bernardino, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'Elia Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Maloberti Alessandro, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Rivasi Giulia, Salvetti Massimo, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  OBJECTIVE:
  The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.
  
  METHODS:
  The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3?±?66.9 months.
  
  RESULTS:
  A total of 23?467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70?mg/dl), in women (>5.26?mg/dl) and in men (>5.49?mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P?=?0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P?0.01), but not in men.
  
  CONCLUSION:
  The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
  
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• Evaluation of Unattended Automated Office, Conventional Office and Ambulatory Blood Pressure Measurements and Their Correlation with Target Organ Damage in an Outpatient Population of Hypertensives: Study Design and Methodological Aspects.
  High Blood Press Cardiovasc Prev

  2019 Dec;26(6):493-499. doi: 10.1007/s40292-019-00344-2.
  
  Mancusi Costantino, Saladini Francesca, Pucci Giacomo, Bertacchini Fabio, Bisogni Valeria, Bruno Rosa Maria, Rivasi Giulia, Maloberti Alessandro, Manzi Maria Virginia, Rosticci Martina, Monticone Silvia, de Feo Martina, Del Pinto Rita, Geraci Giulio, Canciello Grazia, Pengo Martino, Parati Gianfranco,
  
  Abstract
  
  Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study "Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives". This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.
  
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• Cardiovascular Remodeling after Endovascular Treatment for Thoracic Aortic Injury.
  Ann Vasc Surg

  2019 Nov;61():134-141. doi: 10.1016/j.avsg.2019.04.015.
  
  Vallerio Paola, Maloberti Alessandro, D'Alessio Ilenia, Lista Alfredo, Varrenti Marisa, Castelnuovo Samuela, Marone Matteo, Piccinelli Enrico, Grassi Guido, Palmieri Bruno, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  Thoracic endovascular aortic repair (TEVAR) currently represents the gold standard of treatment for thoracic aortic injury (TAI). Nevertheless, there is an ongoing debate surrounding its safety and subsequent cardiovascular effects. Our aim is to assess heart and vascular structure and function remodeling after TEVAR in TAI young patients.
  
  METHODS:
  We evaluated 20 patients (18 men, age 41 ± 14 years, 11 treated with Gore CTAG, 9 with Medtronic Valiant) with office and 24-hr blood pressure (BP) with specific vascular stiffness analysis (Mobil-O-Graph), aortic diameters (computed tomography scan) and left ventricular mass index (LVMI echocardiogram). Evaluation was done after a median time of 5.0 ± 3.5 years from the trauma.
  
  RESULTS:
  After TAI 12 patients (55%) developed hypertension. When patients were divided according to treating time, those treated for more than 3 years show higher LVMI, PWV, and ascending aorta dilatation.
  
  CONCLUSIONS:
  Our study shows that TEVAR for TAI is associated with heart and vascular remodeling. The presence of TEVAR modifies aortic functional properties and could induce an increase in BP that can promote aortic and cardiac damage, even in young patients.
  
  Copyright © 2019 Elsevier Inc. All rights reserved.
  
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• Could two-dimensional radial strain be considered as a novel tool to identify pre-clinical hypertrophic cardiomyopathy mutation carriers?
  Int J Cardiovasc Imaging

  2019 Dec;35(12):2167-2175. doi: 10.1007/s10554-019-01668-9.
  
  Santambrogio Gloria Maria, Maloberti Alessandro, Vallerio Paola, Peritore Angelica, Spanò Francesca, Occhi Lucia, Musca Francesco, Belli Oriana, De Chiara Benedetta, Casadei Francesca, Facchetti Rita, Turazza Fabio, Manfredini Emanuela, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph-); Group C (9 patients), healthy subjects (G-/Ph-). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18%?±?9.6 vs. 44.59%?±?12.67 respectively; p-value?0.0001). In basal posterior and basal inferior segments this difference was particularly evident. ROC curves showed for both the involved segments good AUCs (0.931 and 0.861 for basal posterior and inferior GRS respectively) with the best predictive cut-off for basal posterior GRS at 43.65%, while it was 38.4% for basal inferior GRS. Conversely, GLS values were similar in the three group. 2D longitudinal strain is a valid technique to study HCM. Radial strain and particularly basal posterior and inferior segmental reduction could be able to identify mutation carriers in a pre-clinical phase of disease.
  
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• Pulse wave velocity progression over a medium-term follow-up in hypertensives: Focus on uric acid.
  J Clin Hypertens (Greenwich)

  2019 Jul;21(7):975-983. doi: 10.1111/jch.13603.
  
  Maloberti Alessandro, Rebora Paola, Andreano Anita, Vallerio Paola, De Chiara Benedetta, Signorini Stefano, Casati Marco, Besana Silvia, Bombelli Michele, Grassi Guido, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow-up period in hypertensive patients. Specific sex analysis was done due to the well-known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow-up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow-up, despite better BP values (-8.5 ± 24.6 for SBP and -7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P 
  ©2019 Wiley Periodicals, Inc.
  
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• Vascular Aging and Disease of the Large Vessels: Role of Inflammation.
  High Blood Press Cardiovasc Prev

  2019 Jun;26(3):175-182. doi: 10.1007/s40292-019-00318-4.
  
  Maloberti Alessandro, Vallerio Paola, Triglione Nicola, Occhi Lucia, Panzeri Francesco, Bassi Ilaria, Pansera Francesco, Piccinelli Enrico, Peretti Alessio, Garatti Laura, Palazzini Matteo, Sun Jinwei, Grasso Enzo, Giannattasio Cristina
  
  Abstract
  
  Structural and functional arterial properties commonly impair with aging process. These effects on vasculature could act at many levels from microcirculation to large vessels. Above normal aging process classic cardio-vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, etc.) accelerate the physiological process leading to premature structural and functional alterations that has also been termed early vascular aging. Target organ damage evaluation could be clinically important since these alterations precede by many years' cardiovascular events and so their assessment can predict the onset of more serious and costly events giving the opportunity to prevent CV events by earlier therapeutic intervention. This review will focus on large artery functional properties and particularly on the role of inflammation on the aortic stiffening process.
  
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• Kounis Syndrome: Report of Two Cases with Peculiar Presentation and Diagnostic Issues.
  High Blood Press Cardiovasc Prev

  2019 Apr;26(2):145-149. doi: 10.1007/s40292-019-00312-w.
  
  Maloberti Alessandro, Pansera Francesco, Sala Oscar, Fusco Rossana, Pierri Alessandra, Bossi Irene, Giannattasio Cristina
  
  
  
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• Relationship between vascular damage and left ventricular concentric geometry in patients undergoing coronary angiography: a multicenter prospective study.
  J Hypertens

  2019 Jun;37(6):1183-1190. doi: 10.1097/HJH.0000000000002052.
  
  Salvetti Massimo, Paini Anna, Facchetti Rita, Moreo Antonella, Carerj Scipione, Maloberti Alessandro, Gaibazzi Nicola, Faggiano Pompilio, Mureddu Gianfranco, Rigo Fausto, Giannattasio Cristina, Muiesan Maria Lorenza,
  
  Abstract
  
  BACKGROUND:
  Vascular structural (intima-media thickness) and functional (carotid pulse wave velocity, cPWV) alterations are related to different patterns of left ventricular (LV) geometry in general population samples and in hypertensive patients. The relationship between vascular damage, evaluated by both echotracking ultrasound and coronary angiography, and LV geometry has not been prospectively analyzed.
  
  METHODS:
  In eight Italian centers, 399 consecutive patients, without history of prior coronary artery disease and with clinical indication to coronary angiography, prospectively underwent cardiac standard ultrasound examination for the evaluation of LV mass, indexed by height to 2.7 power (LVMi?g/m) and relative wall thickness (RWT), the measurement of Doppler flow in the left anterior descending artery (LAD) and the echocardiographic calcium score (eCS). In all patients measurement of common carotid intima-media thickness (cIMT) and cPWV by carotid ultrasound, with the realtime echotracking system was performed. The noninvasive evaluations were performed blindly to clinical information, before coronary angiography.
  
  RESULTS:
  cIMT and cPWV were higher in patients with concentric LV hypertrophy (LVH) (LVMi???49?g/m in men and ?47?g/m in women and RWT???0.42) as compared with those with normal LVMi and geometry (N: LVMi?49?g/m in men and 50%) was greater in patients with concentric LVH and concentric remodeling, as compared with N. Patients with both concentric LVH and concentric remodeling showed higher values of cIMT and cPWV and distal LAD velocity and a greater prevalence of coronary stenosis (>50%) than patients with RWT less than 0.42.
  
  CONCLUSION:
  Our results further reinforced the observation that in patients undergoing elective coronary angiography, concentric geometry is associated with structural and functional carotid alterations, with higher distal LAD flow velocity and eCS. In this large group of patients, concentric geometry is associated with a greater prevalence of coronary stenosis, as assessed by coronary angiography. These results might contribute to explain the greater cardiovascular risk associated with concentric remodeling and LVH.
  
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• Mycotic coronary aneurysms.
  J Cardiovasc Med (Hagerstown)

  2019 Jan;20(1):10-15. doi: 10.2459/JCM.0000000000000734.
  
  Buono Andrea, Maloberti Alessandro, Bossi Irene M, Piccaluga Emanuela, Piccalò Giacomo, Oreglia Jacopo A, Moreo Antonella, Russo Claudio F, Oliva Fabrizio, Giannattasio Cristina
  
  Abstract
  
  : Mycotic coronary aneurysm is a rare infective disease of arterial vessel walls. Their development could be linked to the presence of an infective endocarditis or could represent a primary infection at the site of an implanted intracoronary stent. Bacterial agents, particularly Staphylococcus aureus, are the most common etiological agents. Due to an aspecific clinical presentation and examination, diagnosis could be challenging. Multiple imaging techniques (both invasive and noninvasive) are often required to reach the final diagnosis. Prognosis is characterized by high morbidity and mortality rates and, in fact, a tempestive treatment is required, although, to date, scanty data concerning the optimal treatment choice are present in literature.
  
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• Gender-related differences in serum uric acid in treated hypertensive patients from central and east European countries: findings from the Blood Pressure control rate and CArdiovascular Risk profilE study.
  J Hypertens

  2019 Feb;37(2):380-388. doi: 10.1097/HJH.0000000000001908.
  
  Redon Pau, Maloberti Alessandro, Facchetti Rita, Redon Josep, Lurbe Empar, Bombelli Michele, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  OBJECTIVE:
  Hyperuricemia has been associated with high blood pressure (BP) values, diabetes mellitus, metabolic syndrome and chronic kidney disease (CKD). In the present study, we assessed the gender-related relationships between serum uric acid (SUA) and cardionephrometabolic variables in central and east European hypertensive patients.
  
  METHODS:
  A total of 3206 treated hypertensive patients with available SUA levels from the BP-CARE study was analyzed. Correlations among SUA, BP values, BP control, diabetes mellitus, metabolic syndrome and CKD were performed according to gender.
  
  RESULTS:
  Twenty-five percent of the whole population showed hyperuricemia (28% in women and 23% in men). These patients were older and showed a greater burden of cardiovascular risk factors (high BP, BMI, glucose, total cholesterol and triglyceridemia). They also showed a greater prevalence of metabolic syndrome, diabetes mellitus, rate of uncontrolled BP, more than high cardiovascular risk and CKD. Prevalence of metabolic syndrome and uncontrolled BP was similar in normouricemic and hyperuricemic women, the latter displaying a higher prevalence of diabetes mellitus, high cardiovascular risk and CKD. Hyperuricemic men were characterized by a greater prevalence of metabolic syndrome, diabetes mellitus, high cardiovascular risk, rate of uncontrolled BP and CKD but not polytherapy. Logistic regression analysis showed that none of the evaluated variables, except CKD, displayed SUA as significant covariate.
  
  CONCLUSION:
  Our findings provide evidence that a high prevalence of hyperuricemia occurs in hypertensive patients from central and east Europe. The data also show that gender-related differences in the association between SUA and cardionephrometabolic variables exist. This is also the case for the relationships between SUA and CKD.
  
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• Evaluation of adhesion molecules and immune parameters in HIV-infected patients treated with an atazanavir/ritonavir- compared with a lopinavir/ritonavir-based regimen.
  J Antimicrob Chemother

  2018 Aug;73(8):2162-2170. doi: 10.1093/jac/dky178.
  
  Squillace Nicola, Trabattoni Daria, Muscatello Antonio, Sabbatini Francesca, Maloberti Alessandro, Giannattasio Cristina, Masetti Michela, Fenizia Claudio, Soria Alessandro, Clerici Mario, Gori Andrea, Bandera Alessandra
  
  Abstract
  
  OBJECTIVES:
  To evaluate changes in pro-atherosclerotic biomarkers and endothelial function in patients initiating two different PI-based regimens as part of ART.
  
  DESIGN:
  Prospective randomized 24?week study. Treatment-naive HIV-infected patients with CD4+ T cell count >250?cells/mm3 started PI-based regimens including atazanavir/ritonavir (Group A) or lopinavir/ritonavir (Group B) and were followed up in an observational follow-up study until week 96.
  
  METHODS:
  The expression of immune activation and adhesion molecules on CD4+ and CD8+ cells and plasma cytokine levels were assessed at weeks 0, 4, 12, 24, 48, 72 and 96. Flow-mediated dilation (FMD), pulse-wave velocity (PWV) and intima-media thickness (IMT) were measured at weeks 0 and 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated.
  
  RESULTS:
  Twenty-seven patients were enrolled, of whom 15 were treated with atazanavir/ritonavir and 12 with lopinavir/ritonavir. After 96?weeks of ART, CD25+/CD8+ T cells and plasma concentration of MCP-1/CCL-2 rose whereas CD44+/CD8+ T cells decreased significantly in both groups. Differences between treatments were noted for HLA-DRII+/CD8+, CD44+/CD4+ and CD11a+/CD4+, with significant increases in Group B versus Group A. No differences between groups regarding IMT, PWV and FMD were found at baseline and week 24.
  
  CONCLUSIONS:
  ART initiation with PI-based regimens led to a decrease in pro-atherosclerotic biomarkers at week 24, which then rebounded at week 96. Lopinavir/ritonavir treatment resulted in an unfavourable modulation of such markers compared with atazanavir/ritonavir treatment.
  
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• Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room.
  High Blood Press Cardiovasc Prev

  2018 Jun;25(2):177-189. doi: 10.1007/s40292-018-0261-4.
  
  Maloberti Alessandro, Cassano Giulio, Capsoni Nicolò, Gheda Silvia, Magni Gloria, Azin Giulia Maria, Zacchino Massimo, Rossi Adriano, Campanella Carlo, Beretta Andrea Luigi Roberto, Bellone Andrea, Giannattasio Cristina
  
  Abstract
  
  Hypertensive urgencies-emergencies are important and common events. They are defined as a severe elevation in BP, higher than 180/120 mmHg, associated or not with the evidence of new or worsening organ damage for emergencies and urgencies respectively. Anamnestic information, physical examination and instrumental evaluation determine the following management that could need oral (for urgencies) or intravenous (for emergencies) anti-hypertensives drugs. The choice of the specific drugs depend on the underlying causes of the crisis, patient's demographics, cardiovascular risk and comorbidities. For emergencies a maximum BP reduction of 20-25% within the first hour and then to 160/110-100 over next 2-6 h, is considered appropriate with a further gradual decrease over the next 24-48 h to reach normal BP levels. In the case of hypertensive urgencies, a gradual lowering of BP over 24-48 h with an oral medication is the best approach and an aggressive BP lowering should be avoided. Subsequent management with particular attention on chronic BP values control is important as the right treatment of the acute phase.
  
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• In healthy normotensive subjects age and blood pressure better predict subclinical vascular and cardiac organ damage than atherosclerosis biomarkers.
  Blood Press

  2018 Oct;27(5):262-270. doi: 10.1080/08037051.2018.1461010.
  
  Maloberti Alessandro, Farina Francesca, Carbonaro Marco, Piccinelli Enrico, Bassi Ilaria, Pansera Francesco, Grassi Guido, Mancia Giuseppe, Palestini Paola, Giannattasio Cristina
  
  Abstract
  
  PURPOSE:
  Only few studies evaluated biomarkers useful for defining the cardiovascular risk of a subject in a pre-clinical condition (i.e. healthy subjects). In this context we sought to determine the relationships of Plasminogen activator inhibitor type 1 (PAI-1), P-Selectin, Tissue Inhibitors Metalloproteinases type 1 (TIMP-1) and Cystatin-C with subclinical Target Organ Damage (TOD) in normotensive and normoglycemic subjects without known cardiovascular and kidney diseases.
  
  MATERIALS AND METHODS:
  480 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Hypertrophy (LVH) and Intima Media Thickness (IMT) and carotid plaque presence) grouped together under carotid TOD.
  
  RESULTS:
  3.1% of the subjects showed a PWV higher than 10?m/sec with those subjects exerting significantly lower values of P-Selectine (0.068?±?0.015 vs 0.08?±?0.036?mg/L, p?=?.014). 8.8% of the subjects showed carotid TOD that was associated with higher Cystatin-C values (0.67?±?0.17 vs 0.63?±?0.14?mg/L, p?=?.045). Finally 23.8% of the subjects showed LVH with no significant differences regarding biomarkers. Despite some significant correlations between biomarkers and TOD, at the multivariate analysis none came out to be as significant predictor of the assessed TOD.
  
  CONCLUSIONS:
  in normotensive and normoglycemic healthy subjects, the evaluated biomarkers of atherosclerotic process didn't show any significant association with cardiac, carotid and vascular TOD while age and BP are its principal predictors.
  
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• Association Between Atrial, Ventricular and Vascular Morphofunctional Alterations in Rheumatoid Arthritis.
  High Blood Press Cardiovasc Prev

  2018 Mar;25(1):97-104. doi: 10.1007/s40292-017-0246-8.
  
  Maloberti Alessandro, Riva Marta, Tadic Marijana, Valena Carlo, Villa Paolo, Boggioni Ilenia, Pozzi Maria Rosa, Grassi Guido
  
  Abstract
  
  INTRODUCTION:
  Rheumatoid arthritis (RA) represents a risk of non-fatal and cardiovascular events. The aim of the present study was to evaluate simultaneously left and right atrial and ventricular function, as well as arterial stiffness, in RA patients.
  
  METHODS:
  This cross-sectional study included 55 consecutive RA patients and 55 healthy age and gender-matched controls. Blood pressure and arterial stiffness were assessed in all participants, who also underwent a complete echocardiographic examination.
  
  RESULTS:
  RA patients were treated with steroid therapy (52.7%), methotrexate (66.6%) and biological therapy (54.5%). Disease activity score revealed low average RA activity. Augmentation index was significantly higher in RA patients (32.2 ± 8.6 vs. 28.4 ± 8.9%, P = 0.02). Left atrial volume was also higher among RA patients (23.1 ± 8.2 vs. 20.1 ± 7.1 ml/m, P = 0.04), whereas mitral and tricuspid E/A ratios were significantly lower in RA individuals (0.90 ± 0.24 vs. 1.03 ± 0.35, P = 0.02; 1.07 ± 0.31 vs. 1.27 ± 0.35, P = 0.003, respectively). Tissue Doppler systolic and diastolic velocities were similar between the observed groups. Arterial stiffness index showed significant correlation with disease duration (r = 0.29; P = 0.03). Tissue Doppler-derived transmitral late diastolic velocity (A') showed significant correlation with index of disease activity in the RA patients.
  
  CONCLUSIONS:
  Our results showed that left and right ventricular diastolic function and arterial stiffness were significantly deteriorated in the RA patients comparing with controls. The assessment of left and right ventricular diastolic function, as well as vascular function, should be an essential part of clinical evaluation in the RA patients.
  
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• Sex-related relationships between uric acid and target organ damage in hypertension.
  J Clin Hypertens (Greenwich)

  2018 Jan;20(1):193-200. doi: 10.1111/jch.13136.
  
  Maloberti Alessandro, Maggioni Simone, Occhi Lucia, Triglione Nicola, Panzeri Francesco, Nava Stefano, Signorini Stefano, Falbo Rosanna, Casati Marco, Grassi Guido, Giannattasio Cristina
  
  Abstract
  
  Heterogeneous results have been obtained in the relationship between serum uric acid (SUA) and target organ damage (TOD) in patients with hypertension. Clinic blood pressure, SUA, and cardiac, arterial (carotid and aortic), and renal TOD were assessed in 762 consecutive patients with hypertension. Hyperuricemia was defined as an SUA >7.0 in men and >6.0 mg/dL in women. Men with hyperuricemia compared with those with normal SUA showed lower estimated glomerular filtration rates and E/A ratios and a higher prevalence of carotid plaques. Women with hyperuricemia showed lower estimated glomerular filtration rates and E/A ratios and a higher intima-media thickness. Except for pulse wave velocity, all TODs significantly correlated with SUA. However, at multivariate analysis, only estimated glomerular filtration rate was significantly determined by SUA. Our data provide evidence on the role of SUA in the development of TOD only in the case of renal alteration. It is likely that SUA may indirectly act on the other TODs through the increase in blood pressure and the decrease in glomerular filtration rate.
  
  ©2017 Wiley Periodicals, Inc.
  
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• Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular Mass: A Prospective Multicenter Study.
  Hypertension

  2017 Dec;70(6):1157-1164. doi: 10.1161/HYPERTENSIONAHA.117.09917.
  
  Weber Thomas, Wassertheurer Siegfried, Schmidt-Trucksäss Arno, Rodilla Enrique, Ablasser Cornelia, Jankowski Piotr, Lorenza Muiesan Maria, Giannattasio Cristina, Mang Claudia, Wilkinson Ian, Kellermair Jörg, Hametner Bernhard, Pascual Jose Maria, Zweiker Robert, Czarnecka Danuta, Paini Anna, Salvetti Massimo, Maloberti Alessandro, McEniery Carmel
  
  Abstract
  
  UNLABELLED:
  We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm?Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm?Hg, respectively. Mean left ventricular mass was 93.3 kg/m, and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively (=0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively (=0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure.
  
  CLINICAL TRIAL REGISTRATION:
  URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732.
  
  © 2017 American Heart Association, Inc.
  
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• Determinants of carotid-femoral pulse wave velocity progression in hypertensive patients over a 3.7 years follow-up.
  Blood Press

  2018 Feb;27(1):32-40. doi: 10.1080/08037051.2017.1378069.
  
  Meani Paolo, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Giupponi Luca, Stucchi Miriam, Varrenti Marisa, Vallerio Paola, Facchetti Rita, Grassi Guido, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVE:
  The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects.
  
  MATERIALS AND METHODS:
  We enrolled 333 consecutive hypertensive outpatients 18-80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75?±?0.53 years.
  
  RESULTS:
  At baseline the mean age was 54.5?±?12.6 years, SBP and DBP were 141.3?±?18.6 and 86.4?±?10.4?mmHg and PWV was 8.56?±?1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (?PWV 0.87?±?3.05 m/s). PWV and ?PWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ?PWV showed a greater increase as compared to patients with controlled BP (1.46?±?3.67 vs 0.62?±?2.61 m/s, p?.05). The independent predictors of ?PWV were age, baseline PWV, baseline SBP/MBP and ?SBP/MBP.
  
  CONCLUSIONS:
  the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.
  
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• Long-term Saxagliptin Treatment Improves Endothelial Function but not Pulse Wave Velocity and Intima-Media Thickness in Type 2 Diabetic Patients.
  High Blood Press Cardiovasc Prev

  2017 Dec;24(4):393-400. doi: 10.1007/s40292-017-0215-2.
  
  Dell'Oro Raffaella, Maloberti Alessandro, Nicoli Francesco, Villa Paolo, Gamba Pierluigi, Bombelli Michele, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  INTRODUCTION:
  Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes.
  
  AIM:
  We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables.
  
  METHODS:
  In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls.
  
  RESULTS:
  The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P 
  CONCLUSIONS:
  Thus treatment with S added-on to metformin results in beneficial effects on endothelial function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process.
  
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• Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
  High Blood Press Cardiovasc Prev

  2017 Mar;24(1):19-27. doi: 10.1007/s40292-016-0176-x.
  
  Bruschi Giuseppe, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Nava Stefano, Vallerio Paola, Casadei Francesca, Bruno Jolie, Moreo Antonella, Merlanti Bruno, Russo Claudio, Oliva Fabrizio, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS.
  
  AIM:
  We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI).
  
  METHODS:
  30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated.
  
  RESULTS:
  On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: -42.9 ± 17.2 vs -27.9 ± 10.1, peak: -68.7 ± 29.2 vs -42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup.
  
  CONCLUSIONS:
  In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.
  
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• Annexin A5 in treated hypertensive patients and its association with target organ damage.
  J Hypertens

  2017 Jan;35(1):154-161.
  
  Maloberti Alessandro, Meani Paolo, Vallerio Paola, Varrenti Marisa, Casadei Francesca, Musca Francesco, Facchetti Rita, Di Blasio Anna M, Ravassa Susanna, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVE:
  Annexin A5 (AnxA5) has been previously linked to the presence of carotid and cardiac target organ damage (TOD) in the context of heart failure and rheumatologic patients. However, information is scant in the context of hypertension. Aim of our study was to evaluate AnxA5 in treated hypertension patients compared with normotensive controls and to determine whether it is associated with vascular and heart TOD evaluated as arterial stiffness, carotid plaque and left ventricular hypertrophy.
  
  METHODS:
  We enrolled 123 consecutive treated hypertension and 124 normotensive controls. TOD was evaluated as pulse wave velocity (PWV, complior), left ventricular hypertrophy (echocardiography) and intima-media thickness and carotid plaque presence (ecographic methods). AnxA5 levels was dosed and compared in patients with and without hypertension and with and without TOD.
  
  RESULTS:
  With similar age hypertension patients showed higher SBP, DBP and AnxA5 levels (13.9?±?11.1 vs 10.1?±?8.4?ng/ml, P?0.001) compared with controls. Regarding TOD hypertension showed higher PWV (8.5?±?1.8 vs 7.6?±?1.5?m/s, P?0.001) and LVMI (121.7?±?29.3 vs 113.5?±?21.1?g/m, P?0.05), whereas carotid intima-media thickness was superimposable. AnxA5 correlates with PWV (r?=?0.13, P?0.05) and DBP (r?=?0.15, P?0.01), whereas it has never been found as a significant independent predictor of TOD in linear regression analysis.
  
  CONCLUSION:
  Our data have shown that AnxA5 levels are increased in treated hypertension patients. In this condition, it is probably released in the plasma as a defensive mechanism through its anti-inflammatory and anticoagulants effects. We found a significant association with arterial stiffness, but AnxA5 was not found to be a significant predictor of TOD.
  
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• Long-Term Effects of Radiotherapy on Arterial Stiffness in Breast Cancer Women.
  Am J Cardiol

  2016 Sep;118(5):771-6. doi: 10.1016/j.amjcard.2016.06.001.
  
  Vallerio Paola, Sarno Laura, Stucchi Miriam, Musca Francesco, Casadei Francesca, Maloberti Alessandro, Lestuzzi Chiara, Mancia Giuseppe, Moreo Antonella, Palazzi Mauro, Giannattasio Cristina
  
  Abstract
  
  Radiotherapy for breast cancer may expose heart and vessels to late radiation-induced complications. Although recent technical progress in radiation therapy (RT) has been associated with drastic reduction in cardiovascular (CV) mortality, the prolonged life expectancy of patients with cancer requires CV evaluation for many years. The aim of our study was to evaluate local changes in vascular and cardiac function because of previous breast RT. We enrolled 43 patients treated with RT 15 years ago for breast cancer. CV risk factors and atherosclerotic carotid damage were investigated in all women. We divided patients into 2 groups: R (n = 25) treated to right breast and L (n = 18) to left breast. All subjects were submitted to standard echocardiography and functional arteries evaluation by carotid-radial pulse-wave velocity (crPWV; Complior) and AIx (Sphygmocor; Atcor Medical). Global mean age was 69.5 ± 8 years old. CV risk factors were equally allocated in 2 groups. No patients had history of cardiac or artery disease. R had a significantly increased crPWV (9.9 ± 1.4 vs 8.9 ± 1.1, p = 0.001) on right arm compared with left arm, and in L group, crPWV was similarly higher on the left arm than on right arm (9.6 ± 1.5 vs 8.9 ± 1.4, p = 0.011). AIx was significantly increased in the ipsilateral arm only in L (32.1 ± 7.6 vs 28.3 ± 6.8, p = 0.05). Central blood pressure estimation was not different in the right and left arms. No correlations were found with hormone therapy or chemotherapy. Our data show a local arterial stiffening because of radiation that can be involved in increased CV risk in breast cancer-treated patients.
  
  Copyright © 2016 Elsevier Inc. All rights reserved.
  
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• Prognostic relevance of electrocardiographic Tpeak-Tend interval in the general and in the hypertensive population: data from the Pressioni Arteriose Monitorate E Loro Associazioni study.
  J Hypertens

  2016 Sep;34(9):1823-30. doi: 10.1097/HJH.0000000000001005.
  
  Bombelli Michele, Maloberti Alessandro, Raina Lara, Facchetti Rita, Boggioni Ilenia, Pizzala Daniela Prata, Cuspidi Cesare, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  BACKGROUND:
  EKG Tpeak-Tend (Tp-Te) interval, an index of transmural dispersion of myocardial repolarization, is gaining interest as possible cardiovascular prognostic variable. Evidence that this is the case in the general population is scanty, however. This was tested in the Pressioni Arteriose Monitorate E Loro Associazioni population.
  
  METHODS AND RESULTS:
  EKG, echocardiographic, office, home and ambulatory (24-h) blood pressure (BP), metabolic and laboratory data were assessed. Cardiovascular and all-cause mortality were evaluated over a mean follow-up of 16 years. Repetition of all measurements after 10 years allowed to evaluate also the risk of developing office and out-of-office hypertension and echocardiographic left ventricular hypertrophy. At baseline, Tp-Te adjusted for confounders (c) showed a significant correlation with office, home and 24-h blood pressure but not with left ventricular mass. The cTp-Te value predicted the risk of cardiovascular and all-cause mortality before and after adjustment for demographic and clinical variables, the increase being 31 and 13% for 1-SD cTp-Te increase, respectively (P?0.0001 and P?0.002). This was the case also in hypertensive patients in which the corresponding increase in risk with 1-SD increase of Tp-Te was 47 and 25% (P?0.05). cTp-Te did not predict the 10-year risk of developing office, home, ambulatory hypertension and left ventricular hypertrophy.
  
  CONCLUSION:
  Tp-Te interval retains an independent prognostic value both in the general population and in its hypertensive fraction. This easily and cheaply obtainable variable may be employed for improving cardiovascular-risk stratification, representing a useful measure to add to the recommended screening in hypertension.
  
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• Effects of chronic carotid baroreceptor activation on arterial stiffness in severe heart failure.
  Clin Res Cardiol

  2016 Oct;105(10):838-46. doi: 10.1007/s00392-016-0992-y.
  
  Gronda Edoardo, Brambilla GianMaria, Seravalle Gino, Maloberti Alessandro, Cairo Matteo, Costantino Giuseppe, Lovett Eric, Vanoli Emilio, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  BACKGROUND:
  Heart failure with reduced ejection fraction (HFrEF) is characterized by activation of the sympathetic nervous system and increased arterial stiffness, leading to an impaired ventricular-vascular coupling. Baroreflex activation therapy (BAT) has been shown to reduce muscle sympathetic nerve activity (MSNA) and improve clinical status of patients with HFrEF. The purpose of this investigation was to determine the effects of BAT on arterial stiffness in HFrEF.
  
  METHODS AND RESULTS:
  MSNA, clinical variables, and parameters of central blood pressure (BP) and arterial stiffness were collected in 18 NYHA Class III HFrEF patients, nine receiving BAT and nine continuing with optimal medical management alone. Patients were followed for 3 months, with measurements at that time compared to baseline evaluation. Baseline characteristics of the groups were well matched. At 3 months, BAT did not improve central BP and arterial stiffness despite a significant amelioration of MSNA, NYHA class, Minnesota living with heart failure questionnaire score, number of heart failure medications and six-minute walking distance. The control group exhibited no significant changes in all the measured variables.
  
  CONCLUSIONS:
  Despite significant reductions in MSNA and clinical improvement, BAT does not appear to chronically modify arterial stiffness within this HFrEF cohort. Additional study is required to determine if this result applies to the HFrEF population as a whole.
  
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• Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel.
  Interact Cardiovasc Thorac Surg

  2016 Mar;22(3):371-3. doi: 10.1093/icvts/ivv349.
  
  Maloberti Alessandro, Oliva Fabrizio, De Chiara Benedetta, Giannattasio Cristina
  
  Abstract
  
  Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40-year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 × 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, ?-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control.
  
  © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• Erratum to: Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):451. doi: 10.1007/s40292-015-0124-1.
  
  Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
  
  
  
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• A case of Pseudomonas Aeruginosa commercial tattoo infection.
  G Ital Dermatol Venereol

  2018 Apr;153(2):301-302. doi: 10.23736/S0392-0488.17.04937-9.
  
  Maloberti Alessandro, Betelli Mauro, Perego Maria R, Foresti Sergio, Scarabelli Gabriele, Grassi Guido
  
  
  
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• Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):411-6. doi: 10.1007/s40292-015-0121-4.
  
  Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  Renal denervation (RD) is an intriguing treatment strategy for resistant hypertension. However, limited data are available about its long time efficacy as well as its effects on intermediate phenotypes like arterial stiffness and carotid IMT. 12 patients (9 males, mean 69 years) with resistant hypertension underwent bilateral RDN (Medtronic System) since April 2012 in Niguarda Ca' Granda Hospital (Milan). Patients were studied before intervention, and at 1, 3, 6 and 12 months after RD. Carotid intima media thickness (Esaote Mylab) and carotid-femoral pulse wave velocity (Complior, Alam medical) were assessed at each step. Compared to baseline, patients showed a marked reduction of office systolic blood pressure at each follow-up step (p
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• Within-visit BP variability, cardiovascular risk factors, and BP control in central and eastern Europe: findings from the BP-CARE study.
  J Hypertens

  2015 Nov;33(11):2250-6. doi: 10.1097/HJH.0000000000000700.
  
  Grassi Guido, Seravalle Gino, Maloberti Alessandro, Facchetti Rita, Cuspidi Cesare, Bombelli Michele, Laurent Stephane, Redon Josep, Mancia Giuseppe
  
  Abstract
  
  INTRODUCTION AND OBJECTIVE:
  Blood pressure variability (BPV) within 24?h or between visits has been found to represent an independent risk factor for cardiovascular disease. The present study was aimed at determining whether a clinical significance can be given also to the BP variations occurring within a single clinical visit.
  
  METHODS:
  BPV was quantified as coefficient of variation and as standard deviation (SD) of the mean of three systolic SBP values within a visit in the context of a large-cross subclinical survey (BP-CARE) of treated hypertensive patients living in Eastern European countries. The study population was divided into coefficient of variation and SD quartiles and for each quartile a relationship was sought with a large number of cardiovascular risk factors based on patients' history, physical and laboratory examinations.
  
  RESULTS:
  The 6425 hypertensive patients had an age of 59.2?±?11 years (mean?±?SD); they were equally distributed by sex and displayed an average SD and coefficient of variation amounting to 5.1?±?6.2?mmHg and 3.5?±?4.0%, respectively. Compared with the lowest coefficient of variation quartile (Q1), patients in the highest quartile (Q4) showed a significantly greater prevalence of several cardiovascular risk factors, such as age (Q1: 58.5?±?11 vs. Q4: 60.3?±?11 years, P?0.001), serum total cholesterol (Q1: 213.0?±?46 vs. Q4: 216.4?±?51?mg/dl, P?0.05), blood glucose (Q1: 106.2?±?35 vs. Q4: 109.8?±?39?mg/dl, P?0.005), previous cardiovascular events (Q1: 57.4 vs. Q4: 63.9%, P?0.001), and resistant hypertension (Q1: 26.3 vs. Q4: 34.1%, P?0.001). They also showed higher office (Q1: 143.2?±?18 vs. Q4: 154.3?±?19?mmHg, P?0.001) and 24-h ambulatory SBP values (Q1: 134.8?±?17 vs. Q4: 141.2?±?18?mmHg, P?0.001). Similar results were obtained when BPV was expressed as SD.
  
  CONCLUSION:
  Our study provides evidence that greater within-visit BP variabilities are associated with a worse cardiovascular risk profile. This suggests that even this type of BPV may have clinical significance.
  
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• Iron Stores, Hepcidin, and Aortic Stiffness in Individuals with Hypertension.
  PLoS One

  2015 ;10(8):e0134635. doi: e0134635.
  
  Valenti Luca, Maloberti Alessandro, Signorini Stefano, Milano Marta, Cesana Francesca, Cappellini Fabrizio, Dongiovanni Paola, Porzio Marianna, Soriano Francesco, Brambilla Maura, Cesana Giancarlo, Brambilla Paolo, Giannattasio Cristina, Fargion Silvia
  
  Abstract
  
  BACKGROUND & AIMS:
  Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension.
  
  METHODS:
  Circulating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension.
  
  RESULTS:
  At univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p
  CONCLUSIONS:
  In conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness.
  
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• Effects of Cancer Therapy Targeting Vascular Endothelial Growth Factor Receptor on Central Blood Pressure and Cardiovascular System.
  Am J Hypertens

  2016 Feb;29(2):158-62. doi: 10.1093/ajh/hpv077.
  
  Moreo Antonella, Vallerio Paola, Ricotta Riccardo, Stucchi Miriam, Pozzi Mattia, Musca Francesco, Meani Paolo, Maloberti Alessandro, Facchetti Rita, Di Bella Sara, Giganti Maria Olga, Sartore-Bianchi Andrea, Siena Salvatore, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  In the last 2 decades, new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. The aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs.
  
  METHODS:
  Twenty-nine patients (27 affected by renal and 2 by thyroid cancer), received treatment with anti-VEGFR drugs. Brachial blood pressure (BP), central BP, carotid-femoral pulse wave velocity (cfPWV), augmentation index (Aix), and several echocardiographic markers of systolic and diastolic left ventricular functions including global longitudinal strain were measured before starting treatment (T0), after 2 (T1), and 6 weeks (T2) of treatment.
  
  RESULTS:
  Anti-VEGFR treatment was accompanied by a significant increase of both peripheral (systolic BP +13±15.5mm Hg, diastolic BP +7.1±9.3mm Hg, P
  CONCLUSIONS:
  All the changes regarding BP and cfPWV appear early after treatment initiation and seem to be reversible if treatment is stopped, instead diastolic and systolic left ventricular function are persistently altered by anti-VEGFR drugs.
  
  © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
  
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• Clinical value of NT-proBNP assay in the emergency department for the diagnosis of heart failure (HF) in very elderly people.
  Arch Gerontol Geriatr

  2015 ;61(2):296-300. doi: 10.1016/j.archger.2015.05.001.
  
  Bombelli Michele, Maloberti Alessandro, Rossi Stefano, Rea Federico, Corrao Giovanni, Bonicelli Della Vite Carlo, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  OBJECTIVE:
  Scanty data are available on the accuracy of NT-proBNP in the diagnosis of HF and effects of comorbidities in very elderly patients.
  
  METHODS:
  Symptoms, signs, NT-proBNP, eGFR, Ht, CRP and the presence of cardiomegaly and pleuric effusion were assessed in 895 consecutive patients aged 86±4.3 years admitted to Emergency Department and used to define the diagnosis of HF according to Framingham criteria. Receiver operating characteristic curves (ROC) were used to calculate diagnostic performance and cutoff of NT-proBNP. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were computed for all NT-proBNP cutoffs.
  
  RESULTS:
  Satisfactory diagnostic performance was obtained with a lower threshold of 980pg/mL (Sn 0.95; NPV 0.90) and a higher threshold of 5340 (Sp 0.85; PPV 0.76) but with 42.4% of patients in the uncertainty area. We determined a second couple of cutoffs (1470-4200) that reduced the gray-area to 27.4%, maintaining an acceptable diagnostic performance compared to commonly used cutoffs (300-1800). Ht, CRP and eGFR all correlated with NT-proBNP in groups with and without HF but none affected diagnostic performance.
  
  CONCLUSION:
  NT-proBNP performs satisfactorily for the diagnosis of HF in very elderly patients. Proposed threshold couple, compared with the most used cutoffs, showed a gain in Sp and PPV with a slightly lower performance in Sn and NPV and with a decrease in the gray-area with the second one. Our data do not support the use of different NT-proBNP cutoffs depending on eGFR, Ht and CRP.
  
  Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
  
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• Structural and Functional Abnormalities of Carotid Artery and Their Relation with EVA Phenomenon.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):373-9. doi: 10.1007/s40292-015-0100-9.
  
  Maloberti Alessandro, Meani Paolo, Varrenti Marisa, Giupponi Luca, Stucchi Miriam, Vallerio Paola, Giannattasio Cristina
  
  Abstract
  
  Early vascular aging is a process characterized by a reduction in arterial elastin with an increase in collagen that has been related to cardiovascular risk factor and can determine an increased arterial stiffness and central blood pressure. It can be measured by several non invasive methods and in different arterial segment. The present paper will focus on functional (local stiffness parameter) and structural (intima media thickness) carotid arteries alterations typically evaluated by ultrasound methods. Methodological, research and clinical issue has been reviewed.
  
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• Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams-Beuren syndrome children.
  J Hypertens

  2015 Apr;33(4):804-9; discussion 809. doi: 10.1097/HJH.0000000000000454.
  
  Maloberti Alessandro, Cesana Francesca, Hametner Bernhard, Dozio Dario, Villa Paolo, Hulpke-Wette Martin, Schwarz Achim, Selicorni Angelo, Wassertheurer Siegfried, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVE:
  Williams-Beuren syndrome (WBS) is a genetic disorder that involves elastin gene causing cardiovascular abnormalities and increased risk. However, data on arterial function in these patients are only few and conflicting. Aim of this study was to evaluate dynamic behaviour of central and peripheral blood pressure (BP) and arterial stiffness parameters early in the course of WBS.
  
  METHODS:
  We enrolled 19 WBS paediatric patients (age 13?±?4 years) and 23 age, height and BP-matched controls (10?±?4 years). We evaluated 24-h ambulatory BP values via an ambulatory blood pressure monitoring (ABPM) system (Mobil-O-Graph) also capable to calculate 24-h central BP and 24-h arterial stiffness parameters. Carotid-femoral PWV (cf-PWV) was assessed in all WBS individuals (Complior).
  
  RESULTS:
  BP values were similar in WBS and control, during the daytime and the night-time. The same behaviour applies to 24-h central BP. However, during the night, WBS showed heart rate values (HR; 78?±?10 vs. 71?±?9?bpm; P?0.03), augmentation index (Aix; 24.6?±?13.5% vs. 16.5?±?8.9%; P?=?0.03) and reflection magnitude (68 5.8 vs. 63.5 8.1; P?=?0.02) higher than controls. The HR, Aix and reflection magnitude reduction in the day-night shift was lower in WBS than in controls. Cf-PWV in WBS children did not differ when compared with their normalized expected value.
  
  CONCLUSION:
  In WBS children, the higher night-time HR, Aix and reflection magnitude and their impaired physiological reduction in the day-night shift suggests an abnormal sympathetic cardiovascular control, an augmented wave reflection and an increase in small arteries resistance. These alterations possibly due to a sympathetic overactivity can be regarded as earlier hallmarks of cardiovascular dysfunction in these patients.
  
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• Brachial and central blood pressure in HIV-infected subjects.
  Hypertens Res

  2015 Jun;38(6):405-12. doi: 10.1038/hr.2015.25.
  
  Maloberti Alessandro, Dozio Dario, Betelli Mauro, Bandera Alessandra, Squillace Nicola, Gori Andrea, Castoldi Giovanna, Stella Andrea, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  HIV infected subjects present an unfavorable cardiovascular (CV) risk profile that is determined by the infection itself, highly active anti-retroviral therapy (HAART) and other factors, such as chronic kidney disease (CKD). Information is scant and contradictory on whether these factors are associated with arterial stiffness and blood pressure (BP) alteration. Our study aimed to evaluate those parameters in HIV-positive subjects both with and without HAART and with and without CKD, which was defined as the presence of microalbuminuria with a normal glomerular filtration rate. We enrolled 94 HIV-infected subjects without known CV risk factors and compared them with 37 control subjects. We recorded brachial and central BP (pulse wave analysis) and pulse wave velocity ( SphygmoCor). HIV-positive subjects of similar ages and with similar BP values showed central pulse pressure values that were significantly greater than those of controls; this was also the case for the Aix value. Central systolic and pulse pressure values and Aix were significantly greater in HIV-positive subjects with HAART and CKD than in the other HIV-positive subgroups and control subjects. PWV was also superimposable between groups when the data were analyzed relative to the presence of HAART and CKD. Our study shows that the unfavorable CV risk profile associated with HIV infection includes an increase in both central BP and Aix. The central BP increase seems to be favored by renal damage, which apparently has a role in the early stages of the disease.
  
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• Metabolic syndrome in human immunodeficiency virus-positive subjects: prevalence, phenotype, and related alterations in arterial structure and function.
  Metab Syndr Relat Disord

  2013 Dec;11(6):403-11. doi: 10.1089/met.2013.0008.
  
  Maloberti Alessandro, Giannattasio Christina, Dozio Dario, Betelli Mauro, Villa Paulo, Nava Stefano, Cesana Francesca, Facchetti Rita, Giupponi Luca, Castagna Francesco, Sabbatini Francesca, Bandera Alessandra, Gori Andre, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  Human immunodeficiency virus (HIV) infection itself and highly active antiretroviral treatment (HAART) have been proposed to be associated with a higher prevalence of metabolic syndrome, but, to date, prevalence and phenotype of metabolic syndrome among HIV subjects and the related structural and functional vascular alterations are not conclusively defined.
  
  METHODS:
  We analyzed the data of 108 HIV-infected subjects without known cardiovascular risk factors: 72 were on HAART (group A, age 46.5±7.5 years, clinical blood pressure 125.7/74.9±11.6/7.8?mmHg) and there 36 in a naïve group (group B, age 40.7±7.9 years, blood pressure 126/75.8±9.8/7.7?mmHg). A total of 224 healthy subjects served as controls (group C, age 44.9±6.9 years, blood pressure 123.7/75.7±9.8/7.1?mmHg). Arterial stiffness was measured by aorto-femoral pulse wave velocity (PWV, sfigmocor), and carotid intima media thickness (IMT) was measured by a semiautomatic echotracking system (Esaote-WTS).
  
  RESULTS:
  Metabolic syndrome was more frequent in HIV-positive subjects than in controls (19.4%, 13.8%, 4.5% for groups A, B, and C; P
  CONCLUSIONS:
  HIV subjects showed a higher prevalence and a different pattern of metabolic syndrome components. HAART, more than HIV infection per se, appeared to be responsible for the increased prevalence of metabolic syndrome and arterial function derangement.
  
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• Does the 9p region affect arterial stiffness? Results from a cohort of hypertensive individuals.
  Blood Press

  2013 Oct;22(5):302-6. doi: 10.3109/08037051.2013.765627.
  
  Cesana Francesca, Nava Stefano, Menni Cristina, Boffi Lucia, Varrenti Marisa, Meani Paolo, Maloberti Alessandro, Grassi Guido, Giannattasio Cristina, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVE:
  Evidence exists that arterial stiffness, i.e. an independent predictor of cardiovascular and all-causes mortality, has a genetic component. The 9p21 region is associated with a greater susceptibility to coronary disease. Whether this can be ascribed to the fact that genes located on chromosome 9p may also regulate arterial stiffness is largely unknown, however. We evaluate the influence of single nucleotide polymorphisms (SNPs) from 9p on carotid-femoral pulse wave velocity (C-F PWV), measured via the Complior method, in a cohort of 821 hypertensive subjects.
  
  DESIGN:
  The selected tagSNPs were screened with a custom-designed 384-plex VeraCode GoldenGate Genotyping assay on Illumina BeadXpress Reader platform. Association analysis was done using PLINK considering C-F PWV as a quantitative trait (linear regression assuming an additive model) adjusting for sex, age, systolic blood pressure and body mass index (BMI). We used false discovery rate (FDR) to account for multiple testing.
  
  RESULTS:
  Although none of the 384 SNPs was significant after adjusting for multiple testing, probably due to the small sample size of the study population, a trend of association with C-F PWV was observed for rs300622 and rs2381640.
  
  CONCLUSIONS:
  These data suggest that SNPs located on chromosome 9p may affect arterial stiffness. Further studies are needed to confirm our finding on a larger sample and define the physiopathological link of the present results.
  
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• Comparison of echotracking and magnetic resonance assessment of abdominal aorta distensibility and relationships with pulse wave velocity.
  Ultrasound Med Biol

  2011 Dec;37(12):1970-6. doi: 10.1016/j.ultrasmedbio.2011.09.009.
  
  Giannattasio Cristina, Cesana Francesca, Maestroni Silvia, Salvioni Alessandra, Maloberti Alessandro, Nava Stefano, Cairo Matteo, Madotto Fabiana, Zerboni Filippo, Sironi Sandro, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  Arterial distensibility can be measured either by echotracking or by nuclear magnetic resonance (MRI). Little information, however, is available on the comparison between the two methods and on the relationships between the results obtained with the two approaches and the arterial stiffness gold standard measurement, i.e., pulse wave velocity (PWV). In 28 normotensive subjects (age 33.0 ± 10.4 years, mean ± SD) we measured aortic diameter 1 cm above iliac bifurcation, aortic pulse pressure by tonometry and calculated arterial distensibility via the Reneman formulae for both methods. Aortic diameter and aortic distensibility were not superimposable and higher values were systematically detected with the MRI approach than with the ultrasound one. However, PWV showed a significant correlation with aortic distensibility values obtained by both methods (r = 0.50 and r = 0.49, p 
  Copyright © 2011. Published by Elsevier Inc.
  
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• Persistence of arterial functional abnormalities after successful coronary revascularization.
  J Hypertens

  2011 Jul;29(7):1374-9. doi: 10.1097/HJH.0b013e328347a0e3.
  
  Giannattasio Cristina, Capra Anna C M, Calchera Ivan, Colombo Virgilio, Cesana Francesca, Nava Stefano, Maloberti Alessandro, Alloni Marta, Facchetti Rita, Trocino Giuseppe, Grassi Guido, Paolini Giovanni, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  In patients with myocardial ischemia and coronary atherosclerosis, arterial stiffness and endothelial function are impaired. Whether these alterations can be favorably affected by successful coronary revascularization is debated.
  
  METHODS:
  We studied 39 hospitalized patients 59.3 ± 3.2 years old (mean ± SEM). In 21 patients with angiographic evidence of significant coronary artery stenosis, revascularization procedures were performed (stenting n = 11 and bypass surgery n = 10). The remaining patients had no significant stenosis and thus served as controls. Prerevascularization measurements included carotido-femoral pulse wave velocity (PWV), radial artery flow-mediated vasodilatation and a complete echocardiographic examination. The same measurements were performed 6 months later. Pharmacological treatment consisted of different cardiovascular drugs and remained substantially unchanged over the 6-month follow-up period.
  
  RESULTS:
  With the exception of an increased left ventricular mass index (LVMI; 130 ± 5.3 versus 105.8 ± 7.2 g/m(2), P
  CONCLUSION:
  Cardiac revascularization has no effect on arterial function, assessed either as arterial stiffness or as flow-mediated vasodilatation. On the contrary, the improvement in coronary blood flow triggers local cardiac changes, namely, a reduction in LVMI and an improvement in diastolic function.
  
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