Maria L Muiesan1, Massimo Salvetti1, Agostino Virdis2, Stefano Masi2, Edoardo Casiglia3,4, Valérie Tikhonoff3,4, Carlo M Barbagallo5, Michele Bombelli6, Arrigo F G Cicero7, Massimo Cirillo8, Pietro Cirillo9, Giovambattista Desideri10, Lanfranco D'Eliak11, Claudio Ferri10, Ferruccio Galletti11, Loreto Gesualdo9, Cristina Giannattasio12,13, Guido Iaccarino14, Francesca Mallamaci15, Alessandro Maloberti12,13, Alberto Mazza16, Pietro Nazzaro17, Paolo Palatini3,4, Gianfranco Parati18, Roberto Pontremoli19, Marcello Rattazzi3,4,20, Giulia Rivasi21, Giuliano Tocci22,23, Andrea Ungar21, Paolo Verdecchia24, Francesca Viazzi19, Massimo Volpe22, Guido Grassi6, Claudio Borghi7. 1. Department of Clinical and Experimental Sciences, University of Brescia, Brescia. 2. Department of Clinical and Experimental Medicine, University of Pisa, Pisa. 3. Department of Medicine, University of Padua. 4. Department of Medicine, Studium Patavinum, University of Padua, Padua. 5. Biomedical Department of Internal Medicine and Specialistics, University of Palermo, Palermo. 6. Department of Medicine and Surgery, Clinica Medica, University of Milano-Bicocca, Monza. 7. Department of Medical and Surgical Science, Alma Mater Studiorum University of Bologna, Bologna. 8. Department 'Scuola Medica Salernitana', University of Salerno, Salerno. 9. Department of Emergency and Organ Transplantation-Nephrology, Dialysis and Transplantation Unit, Aldo Moro University of Bari, Bari. 10. Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila. 11. Department of Clinical Medicine and Surgery, 'Federico II' University of Naples Medical School, Naples. 12. Cardiology IV, 'A.De Gasperis' Department, Niguarda Ca' Granda Hospital. 13. Health Science Department, Milano-Bicocca University, Milan. 14. Department of Advanced Biomedical Sciences, 'Federico II' University of Naples, Naples. 15. Reggio Cal Unit, CNR-IFC, Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Calabria. 16. Department of Internal Medicine, Santa Maria della Misericordia General Hospital, AULSS 5 Polesana, Rovigo. 17. Department of Medical Basic Sciences, Neurosciences and Sense Organs, University of Bari Medical School, Bari. 18. Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital, Istituto Auxologico Italiano & University of Milan-Bicocca, Milan. 19. Department of Internal Medicine, University of Genoa and Policlinico San Martino, Genoa. 20. Medicina Interna I, Ca' Foncello University Hospital, Treviso. 21. Department of Geriatric and Intensive Care Medicine, Careggi Hospital and University of Florence, Florence. 22. Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome. 23. IRCCS Neuromed, Pozzilli. 24. Hospital S. Maria della Misericordia, Perugia, Italy.
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).
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).
Authors: Nerea Becerra-Tomás; Miguel Ruiz-Canela; Pablo Hernández-Alonso; Mònica Bulló; Jun Li; Marta Guasch-Ferré; Estefanía Toledo; Clary B Clish; Ramon Estruch; Emilio Ros; Montserrat Fitó; Chih-Hao Lee; Kerry Pierce; Fernando Arós; Lluís Serra-Majem; Liming Liang; Cristina Razquin; Enrique Gómez-Gracia; Miguel A Martínez-González; Frank B Hu; Dolores Corella; Jordi Salas-Salvadó Journal: Metabolites Date: 2021-05-11