Display options
Cite
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. 2021;doi: 10.1038/s41371-021-00613-5.
Tikhonoff, V., Casiglia, E., Spinella, P., Barbagallo, C. M., Bombelli, M., Cicero, A. F. G., 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. L., 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. (2021). 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, . https://doi.org/10.1038/s41371-021-00613-5
Tikhonoff, Valérie, 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." Journal of human hypertension vol. (2021). doi: https://doi.org/10.1038/s41371-021-00613-5
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. 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. 2021 Sep 29; doi: 10.1038/s41371-021-00613-5. Epub 2021 Sep 29. PMID: 34588603.
Copy Download .nbib Format: NLM
Share it on

J Hum Hypertens. 2021 Sep 29; doi: 10.1038/s41371-021-00613-5. Epub 2021 Sep 29.

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

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,

Affiliations

  1. Department of Medicine, University of Padua, Padua, Italy. [email protected].
  2. Studium Patavinum, Department of Medicine, University of Padua, Padua, Italy.
  3. Department of Medicine, University of Padua, Padua, Italy.
  4. Biomedical Department of Internal Medicine and Specialistics, University of Palermo, Palermo, Italy.
  5. Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
  6. Department of Medical and Surgical Science, Alma Mater Studiorum University of Bologna, Bologna, Italy.
  7. Department of Public Health, "Federico II" University of Naples, Naples, Italy.
  8. Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, "Aldo Moro" University of Bari, Bari, Italy.
  9. Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
  10. Department of Clinical Medicine and Surgery, "Federico II" University of Naples Medical School, Naples, Italy.
  11. Cardiology IV, "A.De Gasperi's" Department, Niguarda Ca' Granda Hospital, Milan, Italy.
  12. School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy.
  13. Department of Advanced Biomedical Sciences, "Federico II" University of Naples, Naples, Italy.
  14. CNR-IFC, Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Cal Unit, Reggio Calabria, Italy.
  15. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
  16. Department of Internal Medicine, Hypertension Unit, General Hospital, Rovigo, Italy.
  17. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  18. Department of Medical Basic Sciences, Neurosciences and Sense Organs, University of Bari Medical School, Bari, Italy.
  19. Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy.
  20. Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
  21. Department of Internal Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  22. Medicina Interna I, Ca' Foncello University Hospital, Treviso, Italy.
  23. Department of Geriatric and Intensive Care Medicine, Careggi Hospital and University of Florence, Florence, Italy.
  24. 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.
  25. IRCCS Neuromed, Pozzilli, Italy.
  26. Hospital S. Maria della Misericordia, Perugia, Italy.

PMID: 34588603 DOI: 10.1038/s41371-021-00613-5

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.

References

  1. Culleton BF, Larson MG, Kannel WB, Levy D. Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med. 1999;131:7–13. - PubMed
  2. Fang J, Alderman MH. Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and Nutrition Examination Survey. JAMA. 2000;283:2404–10. - PubMed
  3. Rahimi-Sakak F, Maroofi M, Rahmani J, Bellissimo N, Hekmatdoost A. Serum uric acid and risk of cardiovascular mortality: a systematic review and dose-response meta-analysis of cohort studies of over a million participants. BMC Cardiovasc Disord. 2019;19:218. - PubMed
  4. Odden MC, Amadu AR, Smit E, Lo L, Peralta CA. Uric acid levels, kidney function, and cardiovascular mortality in US adults: National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 1999–2002. Am J Kidney Dis. 2014;64:550–7. - PubMed
  5. Bos MJ, Koudstaal PJ, Hofman A, Witteman JC, Breteler MM. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke. 2006;37:1503–7. - PubMed
  6. Becker BF. Towards the physiological function of uric acid. Free Radic Biol Med. 1993;14:615e31. - PubMed
  7. Nieto FJ, Iribarren C, Gross MD, Comstock GW, Cutler RG. Uric acid and serum antioxidant capacity: a reaction to atherosclerosis. Atherosclerosis. 2000;148:131e9. - PubMed
  8. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94:1172e9. - PubMed
  9. Li M, Hou W, Zhang X, Hu L, Tang Z. Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis. 2014;232:265–70. - PubMed
  10. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:885–92. - PubMed
  11. Desideri G, Virdis A, Casiglia E, Borghi C. Exploration into uric and cardiovascular disease: Uric Acid Right for heArt Health (URRAH) Project. A study protocol for a retrospective observational study. High Blood Press Cardiovasc Prev. 2018;25:197–202. - PubMed
  12. Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, et al. 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;38:412–9. - PubMed
  13. Virdis A, Masi S, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, et al. Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years. Hypertension. 2020;75:302–8. - PubMed
  14. Muiesan ML, Salvetti M, Virdis A, Masi S, Casiglia E, Tikhonoff V, et al. 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;39:62–9. - PubMed
  15. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12. - PubMed
  16. Casiglia E, Palatini P. Cardiovascular risk factors in the elderly. J Hum Hypertens. 1998;12:575–81. - PubMed
  17. Casiglia E, Spolaore P, Ginocchio G, Colangeli G, Di Menza G, Marchioro M, et al. Predictors of mortality in very old subjects aged 80 years or over. Eur J Epidemiol. 1993;9:577–86. - PubMed
  18. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45. - PubMed
  19. Kamarudin AN, Cox T, Kolamunnage-Dona R, Time-dependent ROC. curve analysis in medical research: current methods and applications. BMC Med Res Methodol. 2017;17:53. - PubMed
  20. Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3:32–5. - PubMed
  21. Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden index to discriminate individuals using pooled blood samples. Epidemiology. 2005;16:73–81. - PubMed
  22. Mazza A, Zamboni S, Tikhonoff V, Schiavon L, Pessina AC, Casiglia E. Body mass index and mortality in elderly men and women from general population. Gerontology. 2007;53:36–45. - PubMed
  23. Maloberti A, Bombelli M, Facchetti R, Desideri G, Cicero AFG, Muiesan ML, et al. Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URRAH (URic acid Right for heArt Health) study. J Hypertens. 2021;39:333–40. - PubMed
  24. Alderman MH, Cohen H, Madhavan S, Kivlighn S. Serum uric acid and cardiovascular events in successfully treated hypertensive patients. Hypertension. 1999;34:144–50. - PubMed
  25. Casiglia E, Mazza A, Tikhonoff V, Pavei A, Privato G, Schenal N, et al. Weak effect of hypertension and other classic risk factors in the elderly who have already paid their toll. J Hum Hypertens. 2002;16:21–31. - PubMed
  26. Zhong C, Zhong X, Xu T, Xu T, Zhang Y. Sex‐specific relationship between serum uric acid and risk of stroke: a dose‐response meta‐analysis of prospective studies. J Am Heart Assoc. 2017;6:pii:e005042. - PubMed
  27. Ruoff G, Edwards NL. Overview of serum uric acid treatment targets in gout: why less than 6 mg/dl? Postgrad Med. 2016;128:706–15. - PubMed
  28. Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64:1431–46. - PubMed
  29. Storhaug HM, Norvik JV, Toft I, Eriksen BO, Løchen ML, Zykova S, et al. Uric acid is a risk factor for ischemic stroke and all-cause mortality in the general population: a gender specific analysis from The Tromsø Study. BMC Cardiovasc Disord. 2013;13:115. - PubMed
  30. Xu Y, Zhu J, Gao L, Liu Y, Shen J, Shen C, et al. Hyperuricemia as an independent predictor of vascular complications and mortality in type 2 diabetes patients: a meta-analysis. PLoS One. 2013;8:e78206. - PubMed
  31. Du L, Ma J, Zhang X. Higher serum uric acid may contribute to cerebral infarction in patients with type 2 diabetes mellitus: a meta-analysis. J Mol Neurosci. 2017;61:25–31. - PubMed
  32. Burnier M, Bakris G, Williams B. Redefining diuretics use in hypertension: why select a thiazide-like diuretic? J Hypertens. 2019;37:1574–86. - PubMed
  33. Jin M, Yang F, Yang I, Yin Y, Luo JJ, Wang H, et al. Uric acid, hyperuricemia and vascular diseases. Front Biosci. 2012;17:656–69. - PubMed
  34. Suarna C, Dean RT, May J, Stocker R. Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of alpha–tocopherol and ascorbate. Arterioscler Thromb Vasc Biol. 1995;15:1616–24. - PubMed
  35. Visy JM, LeCoz P, Chadefaux B, Fressinaud C, Woimant F, Marquet J, et al. Homocystinuria due to 5,10–methylenetetrahydrofolate reductase deficiency revealed by stroke in adult siblings. Neurology. 1991;41:1313–5. - PubMed
  36. Kanbay M, Segal M, Afsar B, Kang DH, Rodriguez-Iturbe B, Johnson RJ. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart. 2013;99:759–66. - PubMed
  37. De Scheeder IK, van de Kraay AM, Lamers JM, Koster JF, deJong JW, Serruys PW. Myocardial malondialdehyde and uric acid release after short-lasting coronary occlusions during angioplasty: potential mechanisms for free radical generation. Am J Cardiol. 1991;68:392–5. - PubMed
  38. Tikhonoff V, Kuznetsova T, Stolarz K, Bianchi G, Casiglia E, Kawecka-Jaszcz K, et al. β-adducin polymorphism, blood pressure, and sodium excretion in three European populations. Am J Hypert. 2003;16:840–6. - PubMed

Publication Types