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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

Journal of Human Hypertension volume 36, pages 976–982 (2022)Cite this article

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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.

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Fig. 1: Receiver-operator-characteristic (ROC) curves of combined cerebrovascular events.
Fig. 2: Kaplan–Meier curves of survival probability for combined cerebrovascular events in the overall population.
Fig. 3: Adjusted hazard ratios with 95% confidence intervals of the combined cerebrovascular events for having serum uric acid >4.79 mg/dL by quintiles of age in models including the interaction term cut-off value of SUA × age and other covariates.

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Funding

This work has been conducted with an unrestricted grant from the Fondazione of the Italian Society of Hypertension (grant: MIOL).

Author information

Author notes

  1. These authors contributed equally: Valérie Tikhonoff, Edoardo Casiglia.

Authors and Affiliations

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

    Valérie Tikhonoff, Paolo Spinella & Marcello Rattazzi

  2. Studium Patavinum, Department of Medicine, University of Padua, Padua, Italy

    Edoardo Casiglia & Paolo Palatini

  3. Biomedical Department of Internal Medicine and Specialistics, University of Palermo, Palermo, Italy

    Carlo M. Barbagallo

  4. Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Michele Bombelli, Fosca Quarti-Trevano & Guido Grassi

  5. Department of Medical and Surgical Science, Alma Mater Studiorum University of Bologna, Bologna, Italy

    Arrigo F. G. Cicero & Claudio Borghi

  6. Department of Public Health, “Federico II” University of Naples, Naples, Italy

    Massimo Cirillo

  7. Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, “Aldo Moro” University of Bari, Bari, Italy

    Pietro Cirillo & Loreto Gesualdo

  8. Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

    Giovambattista Desideri & Claudio Ferri

  9. Department of Clinical Medicine and Surgery, “Federico II” University of Naples Medical School, Naples, Italy

    Lanfranco D’elia & Ferruccio Galletti

  10. Cardiology IV, “A.De Gasperi’s” Department, Niguarda Ca’ Granda Hospital, Milan, Italy

    Cristina Giannattasio & Alessandro Maloberti

  11. School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy

    Cristina Giannattasio & Alessandro Maloberti

  12. Department of Advanced Biomedical Sciences, “Federico II” University of Naples, Naples, Italy

    Guido Iaccarino

  13. CNR-IFC, Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Cal Unit, Reggio Calabria, Italy

    Francesca Mallamaci

  14. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Stefano Masi & Agostino Virdis

  15. Department of Internal Medicine, Hypertension Unit, General Hospital, Rovigo, Italy

    Alberto Mazza

  16. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Maria Lorenza Muiesan & Massimo Salvetti

  17. Department of Medical Basic Sciences, Neurosciences and Sense Organs, University of Bari Medical School, Bari, Italy

    Pietro Nazzaro

  18. Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy

    Gianfranco Parati

  19. Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy

    Gianfranco Parati

  20. Department of Internal Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Roberto Pontremoli & Francesca Viazzi

  21. Medicina Interna I, Ca’ Foncello University Hospital, Treviso, Italy

    Marcello Rattazzi

  22. Department of Geriatric and Intensive Care Medicine, Careggi Hospital and University of Florence, Florence, Italy

    Giulia Rivasi & Andrea Ungar

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

    Giuliano Tocci & Massimo Volpe

  24. IRCCS Neuromed, Pozzilli, Italy

    Giuliano Tocci & Massimo Volpe

  25. Hospital S. Maria della Misericordia, Perugia, Italy

    Paolo Verdecchia

Authors
  1. Valérie Tikhonoff
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  2. Edoardo Casiglia
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  3. Paolo Spinella
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Consortia

Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)

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

Contributions

Conception and design: VT, EC. Acquisition of data: VT, EC, PS, CMB, MB, AFGC, MC, PC, GD, LD, CF, FG, LG, CG, GI, FM, AM, SM, AM, MLM, PN, PP, GP, RP, FQ-T, MR, GR, MS, GT, AU, PV, FV, AV, MV, GG, CB. Analysis and interpretation of data: VT, EC. Drafting of the manuscript or revising it critically for important intellectual content: VT, EC, GB, CF, FG, CG, FM, MLM, PP, GP, RP, AU, PV, AV, MV, GG, CB. Final approval of the manuscript submitted: VT, EC, PS, CMB, MB, AFGC, MC, PC, GD, LD, CF, FG, LG, CG, GI, FM, AM, SM, AM, MLM, PN, PP, GP, RP, FQ-T, MR, GR, MS, GT, AU, PV, FV, AV, MV, GG, GB.

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Correspondence to Valérie Tikhonoff.

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Tikhonoff, V., Casiglia, E., Spinella, P. et al. 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 36, 976–982 (2022). https://doi.org/10.1038/s41371-021-00613-5

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