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Erschienen in:

19.01.2021 | original article

Higher serum uric acid is associated with higher risks of thrombosis and death in patients with primary myelofibrosis

verfasst von: Marko Lucijanic, MD PhD, Ivan Krecak, Davor Galusic, Martina Sedinic, Hrvoje Holik, Vlatka Perisa, Martina Moric Peric, Ivan Zekanovic, Tajana Stoos-Veic, Vlatko Pejsa, Rajko Kusec

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 3-4/2022

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Summary

Background

Serum uric acid (SUA) can promote inflammation and is associated with increased cardiovascular morbidity. Primary (PMF) and secondary myelofibrosis (SMF) are myeloproliferative neoplasms characterized by high cellular turnover and substantial risk of thrombosis and death.

Methods

We have retrospectively investigated SUA in 173 patients with myelofibrosis (125 PMF; 48 SMF) and 30 controls.

Results

The PMF patients had significantly higher SUA in comparison to SMF and controls. In both PMF and SMF higher SUA was significantly associated with arterial hypertension and decreased renal function. Among PMF patients, higher SUA was significantly associated with older age, larger spleen, higher white blood cell counts, higher lactate dehydrogenase, lower immunoglobulin G levels, allopurinol use and non-smoking. Among SMF patients, higher SUA was associated with male sex (P < 0.05 for all analyses).
In PMF higher SUA was univariately associated with inferior survival (> 427 μmol/L hazard ratio (HR) = 2.22; P = 0.006) and shorter time to thrombosis (> 444 μmol/L HR = 5.05; P = 0.006), which could be shown separately for arterial (> 380 μmol/L; HR = 4.9; P = 0.013) and venous thromboses (> 530 μmol/L; HR = 17.9; P < 0.001). In multivariate analyses, SUA remained significantly associated with inferior survival independent of the Dynamic International Prognostic Staging System and with shorter time to thrombosis independent of age in PMF patients; however, the prognostic significance of SUA was diminished after including serum creatinine in the models. SUA was not prognostic in SMF patients.

Conclusion

The PMF patients present with higher SUA levels, which are associated with features of more advanced disease and higher risks of arterial and venous thrombosis and death.
Literatur
1.
Zurück zum Zitat Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRef Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRef
2.
Zurück zum Zitat Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment. Leukemia. 2008;22(2):437–8.CrossRef Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment. Leukemia. 2008;22(2):437–8.CrossRef
4.
Zurück zum Zitat Passamonti F, Giorgino T, Mora B, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31(12):2726–31.CrossRef Passamonti F, Giorgino T, Mora B, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31(12):2726–31.CrossRef
6.
Zurück zum Zitat Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (international working group for myeloproliferative neoplasms research and treatment). Blood. 2010;115(9):1703–8.CrossRef Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (international working group for myeloproliferative neoplasms research and treatment). Blood. 2010;115(9):1703–8.CrossRef
7.
Zurück zum Zitat Barbui T, Thiele J, Gisslinger H, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018;8(2):15.CrossRef Barbui T, Thiele J, Gisslinger H, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018;8(2):15.CrossRef
8.
Zurück zum Zitat Kc D, Falchi L, Verstovsek S. The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: a review. Ann Hematol. 2017;96(10):1595–604.CrossRef Kc D, Falchi L, Verstovsek S. The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: a review. Ann Hematol. 2017;96(10):1595–604.CrossRef
9.
Zurück zum Zitat Lu W, Xu Y, Shao X, et al. Uric acid produces an inflammatory response through activation of NF-kappaB in the hypothalamus: implications for the pathogenesis of metabolic disorders. Sci Rep. 2015;5:12144.CrossRef Lu W, Xu Y, Shao X, et al. Uric acid produces an inflammatory response through activation of NF-kappaB in the hypothalamus: implications for the pathogenesis of metabolic disorders. Sci Rep. 2015;5:12144.CrossRef
10.
Zurück zum Zitat Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359(17):1811–21.CrossRef Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359(17):1811–21.CrossRef
11.
Zurück zum Zitat Krishnan E, Sokolove J. Uric acid in heart disease: a new C‑reactive protein? Curr Opin Rheumatol. 2011;23(2):174–7.CrossRef Krishnan E, Sokolove J. Uric acid in heart disease: a new C‑reactive protein? Curr Opin Rheumatol. 2011;23(2):174–7.CrossRef
13.
Zurück zum Zitat Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128–32.PubMed Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128–32.PubMed
14.
Zurück zum Zitat Lucijanic M, Petrovecki M. Analysis of censored data. Biochem Med. 2012;22(2):151–5.CrossRef Lucijanic M, Petrovecki M. Analysis of censored data. Biochem Med. 2012;22(2):151–5.CrossRef
15.
Zurück zum Zitat Lucijanic M, Skelin M, Lucijanic T. Survival analysis, more than meets the eye. Biochem Med. 2017;27(1):14–8.CrossRef Lucijanic M, Skelin M, Lucijanic T. Survival analysis, more than meets the eye. Biochem Med. 2017;27(1):14–8.CrossRef
16.
Zurück zum Zitat Lucijanic M. Survival analysis in clinical practice: analyze your own data using an Excel workbook. Croat Med J. 2016;57(1):77–9.CrossRef Lucijanic M. Survival analysis in clinical practice: analyze your own data using an Excel workbook. Croat Med J. 2016;57(1):77–9.CrossRef
17.
Zurück zum Zitat Cervantes F, Alvarez-Larran A, Arellano-Rodrigo E, Granell M, Domingo A, Montserrat E. Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a series of 155 patients from a single institution. Leukemia. 2006;20(1):55–60.CrossRef Cervantes F, Alvarez-Larran A, Arellano-Rodrigo E, Granell M, Domingo A, Montserrat E. Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a series of 155 patients from a single institution. Leukemia. 2006;20(1):55–60.CrossRef
18.
Zurück zum Zitat Elliott MA, Pardanani A, Lasho TL, Schwager SM, Tefferi A. Thrombosis in myelofibrosis: prior thrombosis is the only predictive factor and most venous events are provoked. Haematologica. 2010;95(10):1788–91.CrossRef Elliott MA, Pardanani A, Lasho TL, Schwager SM, Tefferi A. Thrombosis in myelofibrosis: prior thrombosis is the only predictive factor and most venous events are provoked. Haematologica. 2010;95(10):1788–91.CrossRef
19.
Zurück zum Zitat Barbui T, Carobbio A, Cervantes F, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–82.CrossRef Barbui T, Carobbio A, Cervantes F, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–82.CrossRef
20.
Zurück zum Zitat Pei YQ, Wu Y, Wang F, Cui W. Prognostic value of CALR vs. JAK2V617F mutations on splenomegaly, leukemic transformation, thrombosis, and overall survival in patients with primary fibrosis: a meta-analysis. Ann Hematol. 2016;95(9):1391–8.CrossRef Pei YQ, Wu Y, Wang F, Cui W. Prognostic value of CALR vs. JAK2V617F mutations on splenomegaly, leukemic transformation, thrombosis, and overall survival in patients with primary fibrosis: a meta-analysis. Ann Hematol. 2016;95(9):1391–8.CrossRef
21.
Zurück zum Zitat Lucijanic M, Galusic D, Krecak I, et al. Reduced renal function strongly affects survival and thrombosis in patients with myelofibrosis. Ann Hematol. 2020;99(12):2779–85.CrossRef Lucijanic M, Galusic D, Krecak I, et al. Reduced renal function strongly affects survival and thrombosis in patients with myelofibrosis. Ann Hematol. 2020;99(12):2779–85.CrossRef
23.
Zurück zum Zitat De Becker B, Borghi C, Burnier M, van de Borne P. Uric acid and hypertension: a focused review and practical recommendations. J Hypertens. 2019;37(5):878–83.CrossRef De Becker B, Borghi C, Burnier M, van de Borne P. Uric acid and hypertension: a focused review and practical recommendations. J Hypertens. 2019;37(5):878–83.CrossRef
24.
Zurück zum Zitat Mazzali M, Kanbay M, Segal MS, et al. Uric acid and hypertension: cause or effect? Curr Rheumatol Rep. 2010;12(2):108–17.CrossRef Mazzali M, Kanbay M, Segal MS, et al. Uric acid and hypertension: cause or effect? Curr Rheumatol Rep. 2010;12(2):108–17.CrossRef
25.
Zurück zum Zitat Khosla UM, Zharikov S, Finch JL, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005;67(5):1739–42.CrossRef Khosla UM, Zharikov S, Finch JL, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005;67(5):1739–42.CrossRef
26.
Zurück zum Zitat George J, Carr E, Davies J, Belch JJ, Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation. 2006;114(23):2508–16.CrossRef George J, Carr E, Davies J, Belch JJ, Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation. 2006;114(23):2508–16.CrossRef
27.
Zurück zum Zitat Guthikonda S, Sinkey C, Barenz T, Haynes WG. Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers. Circulation. 2003;107(3):416–21.CrossRef Guthikonda S, Sinkey C, Barenz T, Haynes WG. Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers. Circulation. 2003;107(3):416–21.CrossRef
28.
Zurück zum Zitat Butler R, Morris AD, Belch JJ, Hill A, Struthers AD. Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension. 2000;35(3):746–51.CrossRef Butler R, Morris AD, Belch JJ, Hill A, Struthers AD. Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension. 2000;35(3):746–51.CrossRef
29.
Zurück zum Zitat Spiga R, Marini MA, Mancuso E, et al. Uric acid is associated with inflammatory biomarkers and induces inflammation via activating the NF-kappaB signaling pathway in hepG2 cells. Arterioscler Thromb Vasc Biol. 2017;37(6):1241–9.CrossRef Spiga R, Marini MA, Mancuso E, et al. Uric acid is associated with inflammatory biomarkers and induces inflammation via activating the NF-kappaB signaling pathway in hepG2 cells. Arterioscler Thromb Vasc Biol. 2017;37(6):1241–9.CrossRef
Metadaten
Titel
Higher serum uric acid is associated with higher risks of thrombosis and death in patients with primary myelofibrosis
verfasst von
Marko Lucijanic, MD PhD
Ivan Krecak
Davor Galusic
Martina Sedinic
Hrvoje Holik
Vlatka Perisa
Martina Moric Peric
Ivan Zekanovic
Tajana Stoos-Veic
Vlatko Pejsa
Rajko Kusec
Publikationsdatum
19.01.2021
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 3-4/2022
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-020-01802-x

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