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

Author

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, and Cirillo, Pietro

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. [ABSTRACT FROM AUTHOR]

Published
2021
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52. Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.

Author

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, and Mallamaci, Francesca

Published
2021
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53. Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKD

Author

Ramspek, Chava L., Evans, Marie, Wanner, Christoph, Drechsler, Christiane, Chesnaye, Nicholas C., Szymczak, Maciej, Krajewska, Magdalena, Torino, Claudia, Porto, Gaetana, Hayward, Samantha, Caskey, Fergus, Dekker, Friedo W., Jager, Kitty J., van Diepen, Merel, Cupisti, Adamasco, Sagliocca, Adelia, Ferraro, Alberto, Musiała, Aleksandra, Mele, Alessandra, Naticchia, Alessandro, Còsaro, Alex, Woodman, Alistair, Ranghino, Andrea, Stucchi, Andrea, Jonsson, Andreas, Schneider, Andreas, Pignataro, Angelo, Schrander, Anita, Torp, Anke, McKeever, Anna, Szymczak, Anna, Blom, Anna-Lena, De Blasio, Antonella, Pani, Antonello, Tsalouichos, Aris, Ullah, Asad, McLaren, Barbara, van Dam, Bastiaan, Iwig, Beate, Antonio, Bellasi, Di Iorio, Biagio Raffaele, Rogland, Björn, Perras, Boris, Alessandra, Butti, Harron, Camille, Wallquist, Carin, Siegert, Carl, Barrett, Carla, Gaillard, Carlo, Garofalo, Carlo, Abaterusso, Cataldo, Beerenhout, Charles, O’Toole, Charlotte, Somma, Chiara, Marx, Christian, Summersgill, Christina, Blaser, Christof, D’alessandro, Claudia, Emde, Claudia, Zullo, Claudia, Pozzi, Claudio, Geddes, Colin, Verburgh, Cornelis, Bergamo, Daniela, Ciurlino, Daniele, Motta, Daria, Glowski, Deborah, McGlynn, Deborah, Vargas, Denes, Krieter, Detlef, Russo, Domenico, Fuchs, Dunja, Sands, Dympna, Hoogeveen, Ellen, Irmler, Ellen, Dimény, Emöke, Favaro, Enrico, Platen, Eva, Olczyk, Ewelina, Hoorn, Ewout, Vigotti, Federica, Ansali, Ferruccio, Conte, Ferruccio, Cianciotta, Francesca, Giacchino, Francesca, Cappellaio, Francesco, Pizzarelli, Francesco, Sundelin, Fredrik, Uhlin, Fredrik, Greco, Gaetano, Roy, Geena, Porto, Gaetana, Bigatti, Giada, Marinangeli, Giancarlo, Cabiddu, Gianfranca, Hirst, Gillian, Fumagalli, Giordano, Caloro, Giorgia, Piccoli, Giorgina, Capasso, Giovanbattista, Gambaro, Giovanni, Tognarelli, Giuliana, Bonforte, Giuseppe, Conte, Giuseppe, Toscano, Giuseppe, Del Rosso, Goffredo, Welander, Gunilla, Augustyniak-Bartosik, Hanna, Boots, Hans, Schmidt-Gürtler, Hans, King, Hayley, McNally, Helen, Schlee, Hendrik, Boom, Henk, Naujoks, Holger, Masri-Senghor, Houda, Murtagh, Hugh, Rayner, Hugh, Miśkowiec-Wiśniewska, Ilona, Schlee, Ines, Capizzi, Irene, Bascaran Hernandez, Isabel, Baragetti, Ivano, Manitius, Jacek, Turner, Jane, Eijgenraam, Jan-Willem, Kooman, Jeroen, Beige, Joachim, Pondel, Joanna, Wilcox, Joanne, Berdeprado, Jocelyn, Röthele, Jochen, Wong, Jonathan, Rotmans, Joris, Banda, Joyce, Mazur, Justyna, Hahn, Kai, Jędrzejak, Kamila, Nowańska, Katarzyna, Blouin, Katja, Neumeier, Katrin, Jones, Kirsteen, Anding-Rost, Kirsten, Gröntoft, Knut-Christian, Oldrizzi, Lamberto, Haydock, Lesley, Vogt, Liffert, Wilkinson, Lily, Gesualdo, Loreto, Schramm, Lothar, Biancone, Luigi, Nowak, Łukasz, Raasveld, Maarten, Durlik, Magdalena, Magnano, Manuela, Vervloet, Marc, Ricardi, Marco, Carmody, Margaret, Di Bari, Maria, Laudato, Maria, Luisa Sirico, Maria, Stendahl, Maria, Svensson, Maria, Weetman, Maria, van Buren, Marjolijn, Joinson, Martin, Ferraresi, Martina, Dutton, Mary, van Diepen, Merel, Matthews, Michael, Provenzano, Michele, Hopf, Monika, Malaguti, Moreno, Wuttke, Nadja, Morgan, Neal, Palmieri, Nicola, Frischmuth, Nikolaus, Bleakley, Nina, Murrone, Paola, Cockwell, Paul, Leurs, Paul, Roderick, Paul, Voskamp, Pauline, Kashioulis, Pavlos, Ichtiaris, Pawlos, Blankestijn, Peter, Kirste, Petra, Schulz, Petra, Mason, Phil, Kalra, Philip, Cirillo, Pietro, Dattolo, Pietro, Acampora, Pina, Sajith, Rincy, Nigro, Rita, Boero, Roberto, Scarpioni, Roberto, Sicoli, Rosa, Malandra, Rosella, Aign, Sabine, Cäsar, Sabine, van Esch, Sadie, Chapman, Sally, Biribauer, Sandra, Navjee, Santee, Crosbie, Sarah, Brown, Sharon, Tickle, Sheila, Manan, Sherin, Röser, Silke, Savoldi, Silvana, Bertoli, Silvio, Borrelli, Silvio, Boorsma, Siska, Heidenreich, Stefan, Melander, Stefan, Maxia, Stefania, Maffei, Stefano, Mangano, Stefano, Palm, Stephanie, Konings, Stijn, Mathavakkannan, Suresh, Schwedler, Susanne, Delrieux, Sylke, Renker, Sylvia, Schättel, Sylvia, Dorota, Szyszkowska, Cicchetti, Teresa, Nieszporek, Teresa, Stephan, Theresa, Schmiedeke, Thomas, Weinreich, Thomas, Leimbach, Til, Rappa, Tiziana, Almquist, Tora, Stövesand, Torsten, Bahner, Udo, Jensen, Ulrika, Palazzo, Valentina, De Simone, Walter, Seeger, Wolfgang, Kuan, Ying, Heleniak, Zbigniew, and Aydin, Zeynep

Published
2021
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54. Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years.

Author

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, and Gesualdo, Loreto

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]; P<0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3-5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99-6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (P<0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM. [ABSTRACT FROM AUTHOR]

Published
2020
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55. Different Abnormalities of Cortical Neural Synchronization Mechanisms in Patients with Mild Cognitive Impairment due to Alzheimer’s and Chronic Kidney Diseases: An EEG Study

Author

Lizio, Roberta, primary, Babiloni, Claudio, additional, Del Percio, Claudio, additional, Losurdo, Antonia, additional, Vernò, Lucia, additional, De Tommaso, Marina, additional, Montemurno, Anna, additional, Dalfino, Giuseppe, additional, Cirillo, Pietro, additional, Soricelli, Andrea, additional, Ferri, Raffaele, additional, Noce, Giuseppe, additional, Pascarelli, Maria Teresa, additional, Catania, Valentina, additional, Nobili, Flavio, additional, Famá, Francesco, additional, Orzi, Francesco, additional, Giubilei, Franco, additional, Buttinelli, Carla, additional, Triggiani, A. Ivano, additional, Frisoni, Giovanni B., additional, Scisci, Anna Maria, additional, Mastrofilippo, Nicola, additional, Procaccini, Deni Aldo, additional, and Gesualdo, Loreto, additional

Published
2018
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56. Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study

Author

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, and 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.

Published
2021
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57. Reply

Author

Cirillo, Pietro, primary, Sautin, Yuri Y., additional, and Johnson, Richard J., additional

Published
2009
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62. Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project

Author

Elisa Russo, Francesca Viazzi, Roberto Pontremoli, Carlo M. Barbagallo, Michele Bombelli, Edoardo Casiglia, Arrigo F. G. Cicero, Massimo Cirillo, Pietro Cirillo, Giovambattista Desideri, Lanfranco D'Elia, Raffaella Dell'Oro, Claudio Ferri, Ferruccio Galletti, Loreto Gesualdo, Cristina Giannattasio, Guido Iaccarino, Giovanna Leoncini, Francesca Mallamaci, Alessandro Maloberti, Stefano Masi, Alessandro Mengozzi, Alberto Mazza, Maria L. Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Marcello Rattazzi, Giulia Rivasi, Massimo Salvetti, Valérie Tikhonoff, Giuliano Tocci, Fosca A. L. Quarti Trevano, Andrea Ungar, Paolo Verdecchia, Agostino Virdis, Massimo Volpe, Guido Grassi, Claudio Borghi, 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, Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Dell'Oro R, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Quarti Trevano FAL, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C., Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Quarti Trevano, F, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, and Elisa Russo, Francesca Viazzi, Roberto Pontremoli, Carlo M Barbagallo, Michele Bombelli, Edoardo Casiglia, Arrigo F G Cicero, Massimo Cirillo, Pietro Cirillo, Giovambattista Desideri, Lanfranco D'Elia, Raffaella Dell'Oro, Claudio Ferri, Ferruccio Galletti, Loreto Gesualdo, Cristina Giannattasio, Guido Iaccarino, Giovanna Leoncini, Francesca Mallamaci, Alessandro Maloberti , Stefano Masi, Alessandro Mengozzi, Alberto Mazza, Maria L Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Marcello Rattazzi, Giulia Rivasi, Massimo Salvetti, Valérie Tikhonoff, Giuliano Tocci, Fosca A L Quarti Trevano, Andrea Ungar, Paolo Verdecchia, Agostino Virdis, Massimo Volpe, Guido Grassi, Claudio Borghi

Subjects
medicine.medical_specialty, hyperuricemia, Cardiovascular Medicine, urologic and male genital diseases, Gastroenterology, albuminuria, chemistry.chemical_compound, cardiovascular mortality, Internal medicine, medicine, eGFR, Diseases of the circulatory (Cardiovascular) system, Hyperuricemia, Risk factor, Original Research, business.industry, Incidence (epidemiology), Confounding, all-cause mortality, hyperuricemia, eGFR, albuminuria, cardiovascular mortality, all-cause mortality, medicine.disease, chemistry, Quartile, RC666-701, Albuminuria, Uric acid, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Kidney disease
Abstract

Background: 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.Methods: 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.Results: 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 Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk.

Published
2021

63. Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project

Author

Maria Masulli, Lanfranco D'Elia, Fabio Angeli, Carlo M. Barbagallo, Giancarlo Bilancio, Michele Bombelli, Berardino Bruno, Edoardo Casiglia, Rosario Cianci, Arrigo F.G. Cicero, Massimo Cirillo, Pietro Cirillo, Raffaella Dell’Oro, Giovambattista Desideri, Claudio Ferri, Loreto Gesualdo, Cristina Giannattasio, Guido Grassi, Guido Iaccarino, Luciano Lippa, Francesca Mallamaci, Alessandro Maloberti, Stefano Masi, Alberto Mazza, Alessandro Mengozzi, Maria Lorenza Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Roberto Pontremoli, Fosca Quarti-Trevano, Marcello Rattazzi, Gianpaolo Reboldi, Giulia Rivasi, Massimo Salvetti, Valerie Tikhonoff, Giuliano Tocci, Andrea Ungar, Paolo Verdecchia, Francesca Viazzi, Agostino Virdis, Massimo Volpe, Claudio Borghi, Ferruccio Galletti, Masulli, M, D'Elia, L, Angeli, F, Barbagallo, C, Bilancio, G, Bombelli, M, Bruno, B, Casiglia, E, Cianci, R, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, Desideri, G, Ferri, C, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Borghi, C, Galletti, F, 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, and Masulli M, D'Elia L, Angeli F, Barbagallo CM, Bilancio G, Bombelli M, Bruno B, Casiglia E, Cianci R, Cicero AFG, Cirillo M, Cirillo P, Dell'Oro R, Desideri G, Ferri C, Gesualdo L, Giannattasio C, Grassi G, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Masi S, Mazza A, Mengozzi A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Reboldi G, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Viazzi F, Virdis A, Volpe M, Borghi C, Galletti F

Subjects
Diabetes mellitu, Nutrition and Dietetics, Settore MED/09 - Medicina Interna, Cardiovascular mortality, Serum uric acid Cardiovascular mortality All-cause mortality Diabetes mellitus Hyperuricemia Diagnostic thresholds, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Hyperuricemia, All-cause mortality, Uric Acid, Diagnostic thresholds, all-cause mortality, cardiovascular mortality, diabetes mellitus, diagnostic thresholds, hyperuricemia, serum uric acid, humans, risk factors, uric acid, Diagnostic threshold, Diabetes mellitus, Serum uric acid, Risk Factors, Humans, Cardiology and Cardiovascular Medicine
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

Published
2022

64. 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

Author

Claudio Ferri, Agostino Virdis, Marcello Rattazzi, Alessandro Maloberti, Arrigo F G Cicero, Massimo Cirillo, Andrea Ungar, Maria Lorenza Muiesan, Pietro Nazzaro, Francesca Viazzi, Giuliano Tocci, Guido Grassi, Ferruccio Galletti, Valérie Tikhonoff, Michele Bombelli, Paolo Verdecchia, Francesca Mallamaci, Giovambattista Desideri, Cristina Giannattasio, Gianfranco Parati, Paolo Palatini, Massimo Salvetti, Carlo M. Barbagallo, Alberto Mazza, Claudio Borghi, Massimo Volpe, Pietro Cirillo, Roberto Pontremoli, Guido Iaccarino, Edoardo Casiglia, Loreto Gesualdo, Giulia Rivasi, Lanfranco D'Eliak, Stefano Masi, Muiesan ML, Salvetti M, Virdis A, Masi S, Casiglia E, Tikhonoff V, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Eliak L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Mallamaci F, Maloberti A, Mazza A, Nazzaro P, Palatini P, Parati G, Pontremoli R, Rattazzi M, Rivasi G, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Muiesan, M, Salvetti, M, Virdis, A, Masi, S, Casiglia, E, Tikhonoff, V, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D’Eliak, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Rattazzi, M, Rivasi, G, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, 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, and Borghi, Claudio

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, Physiology, Epidemiology, Cut-off value, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, 030212 general & internal medicine, Mortality, Risk factor, Cut-off value, heart failure, mortality, uric acid, Heart Failure, business.industry, Proportional hazards model, Hazard ratio, Confounding, cut-off value, heart failure, mortality, uric acid, medicine.disease, Uric Acid, Italy, Heart failure, Cohort, Hypertension, Cardiology, Cardiology and Cardiovascular Medicine, business, Cohort study
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).

Published
2021

65. Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study

Author

Guido Grassi, Francesca Viazzi, Andrea Ungar, Lanfranco D'Elia, Massimo Salvetti, Paolo Spinella, Massimo Volpe, Agostino Virdis, Gianfranco Parati, Roberto Pontremoli, Stefano Masi, Giulia Rivasi, Loreto Gesualdo, Giuliano Tocci, Claudio Ferri, Ferruccio Galletti, Francesca Mallamaci, Alessandro Maloberti, Maria Lorenza Muiesan, Pietro Nazzaro, Valérie Tikhonoff, Michele Bombelli, Massimo Cirillo, Cristina Giannattasio, Paolo Palatini, Carlo M. Barbagallo, Paolo Verdecchia, Marcello Rattazzi, Alberto Mazza, Claudio Borghi, Edoardo Casiglia, Guido Iaccarino, Fosca Quarti-Trevano, Pietro Cirillo, Giovambattista Desideri, Arrigo F G Cicero, 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, Tikhonoff, V, Casiglia, E, Spinella, P, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Grassi, G, Borghi, C, and Tikhonoff V, Casiglia E, Spinella P, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Mallamaci F, Maloberti A, Masi S, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Virdis A, Volpe M, Grassi G, Borghi C

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, uric acid, cardiovascular risk, serum uric acid, stroke, hypertension, cardiovascular prevention, cardiovascular disease, chemistry.chemical_compound, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Stroke, uric acid, hypertension, business.industry, Confounding, Prognosis, medicine.disease, Confidence interval, Uric Acid, chemistry, Hypertension, Uric acid, business, Body mass index, Cohort study, Kidney disease
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.

Published
2021

66. The association of uric acid with mortality modifies at old age: data from the uric acid right for heart health (URRAH) study

Author

Andrea Ungar, Giulia Rivasi, Mauro Di Bari, Agostino Virdis, Edoardo Casiglia, Stefano Masi, Alessandro Mengozzi, Carlo M. Barbagallo, Michele Bombelli, Bernardino Bruno, Arrigo F.G. Cicero, Massimo Cirillo, Pietro Cirillo, Giovambattista Desideri, Lanfranco D’elia, Claudio Ferri, Ferruccio Galletti, Loreto Gesualdo, Cristina Giannattasio, Guido Iaccarino, Michele Ciccarelli, Luciano Lippa, Francesca Mallamaci, Alessandro Maloberti, Alberto Mazza, Maria Lorenza Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Roberto Pontremoli, Fosca Quarti-Trevano, Marcello Rattazzi, Massimo Salvetti, Valérie Tikhonoff, Giuliano Tocci, Rosario Cianci, Paolo Verdecchia, Francesca Viazzi, Massimo Volpe, Guido Grassi, Claudio Borghi, 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, Ungar, A, Rivasi, G, Di Bari, M, Virdis, A, Casiglia, E, Masi, S, Mengozzi, A, Barbagallo, C, Bombelli, M, Bruno, B, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Ciccarelli, M, Lippa, L, Mallamaci, F, Maloberti, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Salvetti, M, Tikhonoff, V, Tocci, G, Cianci, R, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, and Ungar A, Rivasi G, Di Bari M, Virdis A, Casiglia E, Masi S, Mengozzi A, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Ciccarelli M, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Salvetti M, Tikhonoff V, Tocci G, Cianci R, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C

Subjects
Settore MED/09 - Medicina Interna, hypertension, Physiology, Aged, Humans, Prognosis, Proportional Hazards Models, Risk Factors, Uric Acid, uric acid, elderly, cardiovascular prevention, stroke, myocardial infarction, Acid Urc, mortality, old age, Cardiovascular risk, older adult, Cardiovascular prevention, Older adults, Mortality, Uric acid, Internal Medicine, Cardiology and Cardiovascular Medicine
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.

Published
2021

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

Author

Pugliese NR, Mengozzi A, Virdis A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Parati G, Palatini P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Masi S, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Pugliese NR, Mengozzi A, Virdis A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Parati G, Palatini P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Masi S, Borghi C, 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, Georgio, 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, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Cicero AFG, Pugliese, N, Mengozzi, A, Virdis, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Masi, S, and Borghi, C

Subjects
Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Cardiovascular mortality, Prognosi, Sudden cardiac death, chemistry.chemical_compound, Serum uric acid, Risk Factors, Internal medicine, Cause of Death, medicine, Humans, Myocardial infarction, Metabolic syndrome, Prognosis, Stroke, Retrospective Studies, Original Paper, business.industry, Proportional hazards model, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Uric Acid, Survival Rate, chemistry, Italy, Cardiovascular Diseases, Heart failure, Cardiology, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Follow-Up Studies
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 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 p 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. Graphic abstract

Published
2021

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

Author

Massimo Volpe, Luciano Lippa, Andrea Ungar, Francesca Viazzi, Agostino Virdis, Maria Lorenza Muiesan, Georgios Georgiopoulos, Berardino Bruno, Cristina Giannattasio, Loreto Gesualdo, Pietro Nazzaro, Paolo Palatini, Alberto Mazza, Guido Grassi, Massimo Salvetti, Carlo M. Barbagallo, Claudio Borghi, Lanfranco D'Elia, Marcello Rattazzi, Francesca Mallamaci, Arrigo F G Cicero, Ferruccio Galletti, Gianfranco Parati, Alessandro Maloberti, Raffaella Dell'Oro, Alessandro Mengozzi, Giuliano Tocci, Stefano Masi, Giovambattista Desideri, Pietro Cirillo, Valérie Tikhonoff, Michele Bombelli, Gianpaolo Reboldi, Massimo Cirillo, Roberto Pontremoli, Claudio Ferri, Paolo Verdecchia, Edoardo Casiglia, Guido Iaccarino, Fabio Angeli, Giulia Rivasi, Palatini, P, Parati, G, Virdis, A, Reboldi, G, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Angeli, F, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Palatini P, Parati G, Virdis A, Reboldi G, Masi S, Mengozzi A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Angeli F, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Borghi C, 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, Georgio, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, and Borghi, Claudio

Subjects
medicine.medical_specialty, Sympathetic nervous system, Longitudinal study, Epidemiology, Heart rate, 030204 cardiovascular system & hematology, Cardiovascular, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Sympathetic activity, Medicine, 030212 general & internal medicine, Risk factor, Mortality, Proportional hazards model, business.industry, Hazard ratio, Confidence interval, medicine.anatomical_structure, chemistry, Cardiology, Uric acid, Cardiology and Cardiovascular Medicine, business
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 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
2020

69. Serum uric acid and fatal myocardial infarction: Detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study

Author

Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Casiglia, E, Tikhonoff, V, Virdis, A, Masi, S, Barbagallo, C, Bombelli, M, Bruno, B, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., 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, and Borghi, Claudio

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Physiology, cut-off value, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, uric acid, Internal medicine, Internal Medicine, medicine, ORIGINAL PAPERS: Epidemiology, Humans, sex, 030212 general & internal medicine, Hyperuricemia, Myocardial infarction, Risk factor, Aged, Aged, 80 and over, uric acid, cardiovascular, arterial hypertension, cut-off value, mortality, myocardial infarction,sex, uric acid, Proportional hazards model, business.industry, cut-off value, mortality, myocardial infarction, sex, uric acid, Hazard ratio, Middle Aged, medicine.disease, Prognosis, mortality, Confidence interval, Uric acid, myocardial infarction, epidemiology, myocardial infarction, chemistry, Italy, Hypertension, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract

Supplemental Digital Content is available in the text, 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

Published
2020

70. Risk of Cardiovascular Events in Metabolically Healthy Overweight or Obese Adults: Role of LDL-Cholesterol in the Stratification of Risk.

Author

Palatini P, Virdis A, Masi S, Mengozzi A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Parati G, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Masulli M, Verdecchia P, Reboldi G, Angeli F, Cianci R, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Russo E, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Iaccarino G, Nazzaro P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, and Borghi C

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 <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

Published
2024
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71. Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

Author

D'Elia L, Masulli M, Virdis A, Casiglia E, Tikhonoff V, Angeli F, Barbagallo CM, Bombelli M, Cappelli F, Cianci R, Ciccarelli M, Cicero AFG, Cirillo M, Cirillo P, Dell'Oro R, Desideri G, Ferri C, Gesualdo L, Giannattasio C, Grassi G, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Masi S, Mazza A, Mengozzi A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Reboldi G, Rivasi G, Russo E, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Borghi C, and Galletti F

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.)

Published
2024
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72. High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid.

Author

Palatini P, Parati G, Virdis A, Reboldi G, Masi S, Mengozzi A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Angeli F, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, and Borghi C

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

Published
2021
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73. [Gout and chronic kidney disease: specific diagnostic and therapeutic features].

Author

Cirillo P and Gesualdo L

Subjects
Gout complications, Humans, Practice Guidelines as Topic, Gout diagnosis, Gout therapy, Renal Insufficiency, Chronic complications
Abstract

In the last decades, the increase in life expectancy, changes in diet and lifestyle have resulted in raising of incidence and prevalence of gout in all countries. The phenotype of patients with gout has changed a lot over the years: more and more frequently they have several co-morbidities such as hypertension, cardiovascular disease, diabetes, obesity, chronic kidney disease (CKD) and metabolic syndrome that influence the progression and challenge the therapeutic management. The management of gout in CKD patients demands more attention and specific features in diagnosis and therapeutic approach. This article summarizes the most recent published evidences on how to best diagnose and treat the gouty patients with CKD, how to better manage medications for the treatment of acute gouty flares and for the chronic hyperuricemia management.

Published
2015

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