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

Author:

Palatini Paolo1ORCID,Parati Gianfranco2ORCID,Virdis Agostino3ORCID,Reboldi Gianpaolo4,Masi Stefano3,Mengozzi Alessandro3,Casiglia Edoardo5,Tikhonoff Valerie5,Cicero Arrigo F G6,Ungar Andrea7,Rivasi Giulia7,Salvetti Massimo8,Barbagallo Carlo M9,Bombelli Michele1011,Dell’Oro Raffaella1011,Bruno Berardino12,Lippa Luciano13,D’Elia Lanfranco14,Verdecchia Paolo15,Angeli Fabio1617,Mallamaci Francesca18,Cirillo Massimo19,Rattazzi Marcello20ORCID,Cirillo Pietro21,Gesualdo Loreto21,Mazza Alberto22,Giannattasio Cristina2324,Maloberti Alessandro2324,Volpe Massimo2526ORCID,Tocci Giuliano2526ORCID,Georgiopoulos Georgios27,Iaccarino Guido28,Nazzaro Pietro29,Galletti Ferruccio14,Ferri Claudio12,Desideri Giovambattista12,Viazzi Francesca30ORCID,Pontremoli Roberto30,Muiesan Maria Lorenza8,Grassi Guido1011ORCID,Borghi Claudio6ORCID,

Affiliation:

1. Department of Medicine, Studium Patavinum, University of Padova, Via S. Fris 121, 31029 Vittorio Veneto, Italy

2. S. Luca Hospital, Istituto Auxologico Italiano & University of Milan-Bicocca, Milan, Italy

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

4. Department of Medical and Surgical Science, University of Perugia, Perugia, Italy

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

6. Alma Mater Studiorum University of Bologna, Bologna, Italy

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

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

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

10. Department of Cardiovascular, Neural and Metabolic Sciences, Clinica Medica, Monza, Italy

11. Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

12. Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy

13. Italian Society of General, Medicine (SIMG), Avezzano, L’Aquila, Italy

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

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

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

17. Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institutes, IRCCS Tradate, Varese, Italy

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

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

20. Department of Medicine—DIMED, University of Padova, Medicina, Interna 1°, Ca’ Foncello University Hospital, Treviso, Italy

21. Department of Emergency and Organ Transplantation—Nephrology, Dialysis and Transplantation Unit, Aldo Moro University of Bari, Bari, Italy

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

23. Cardiology IV, ‘A. De Gasperis’ Department, Niguarda Ca’ Granda Hospital, Milano, Italy

24. Health Science Department, Milano-Bicocca University, Milano, Italy

25. 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

26. IRCCS Neuromed, Pozzilli (IS), Italy

27. First Department of Cardiology, ‘Hippokration’ Hospital, University of Athens, Medical School, Athens, Greece

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

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

30. Department of Internal Medicine, University of Genoa and Policlinico San Martino, Genova, Italy

Abstract

AbstractAims 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 <median [71.3 b.p.m., adjusted hazard ratio 1.38, 95% confidence interval (CI) 1.20–1.59] than in those with HR ≥median [2.09 (95% CI 1.75–2.51)]. In the participants stratified by HR tertile, the risk related to hyperuricaemia was 2.38 (95% CI 1.82–3.10) in people with HR ≥76 b.p.m. and was 1.24 (95% CI 0.92–1.67) in those with HR <66 b.p.m. Similar results were obtained in the hypertensive patients, in the participants ≥65 years, and in the subjects not taking beta-blockers.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.

Funder

Fondazione of the Italian Society of Hypertension

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Epidemiology

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