Correction of hyperuricemia across stages of gout A rheumatologist‘s perspective – the debate continues
Authors:
K. Pavelka; B. Stibůrková
Authors‘ workplace:
Revmatologický ústav Praha, Revmatologická klinika 1. LF UK, Praha
Published in:
Čes. Revmatol., 33, 2025, No. 3, p. 107-118.
Category:
Rewiev
Overview
Hyperuricemia (HU) affects up to 15% of the general population; however, the prevalence of gout is estimated at 1–10%, depending on geographic region, socioeconomic status, and ethnic background. According to a comprehensive predictive model based on data from 35 countries collected between 1990 and 2020, the global burden of gout is expected to increase by more than 70% between 2020 and 2050, mainly due to population growth and aging. This article provides an overview of available evidence regarding treatment strategies across the different stages of gout. Particular attention is paid to the controversial issue of whether asymptomatic hyperuricemia should be treated. Published data indicate that approximately 24 patients with asymptomatic HU need to be treated to prevent a single gout flare (number needed to treat, NNT = 24). For this reason, most rheumatology guidelines do not recommend pharmacological treatment of asymptomatic hyperuricemia. A different perspective is emerging from the cardiology literature, where multiple epidemiological studies have suggested that hyperuricemia may represent an independent risk factor for increased cardiovascular risk.
The serum urate (s-UA)/serum creatinine (s-Cr) ratio has been proposed as an index of xanthine oxidase/xanthine dehydrogenase (XO) activity, with values > 3.6 indicating increased enzyme activity; such patients may particularly benefit from urate-lowering therapy. Initiation of urate-lowering treatment during an acute gout flare is generally not recommended and should be postponed until inflammatory symptoms have resolved.
Target serum urate levels are < 360 µmol/L for all patients and < 300 µmol/L for those with tophaceous gout.
As prophylaxis against recurrent gout flares, low-dose colchicine is recommended for approximately three months.
Keywords:
gout – hyperuricemia – xanthine oxidase inhibitors
Sources
1. Mikuls TR. Gout. N Engl J Med. 2022; 387(20): 1877–1887.
2. Yokose C, McCormick N, Lu N, et al. Trends in prevalence of gout among US Asian adults, 2011–2018. JAMA Netw Open 2023; 6(4): e239501.
3. Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol. 2015; 11(11): 649–662.
4. Ferguson LD, Molenberghs G, Verbeke G, et al. Gout and inci-dence of 12 cardiovascular diseases: a case-control study including 152 663 individuals with gout and 709 981 matched controls. Lancet Rheumatol. 2024; 6(3): e156–e167.
5. Kvasnička A, Friedecký D, Piskláková B, et al. Ceramide-based risk score: A novel laboratory tool for cardiovascular risk stratification in hyperuricemia and gout. Vascul Pharmacol. 2025; 159 : 107495.
6. Vrablík M, Borghi C, Rosolova8 H, et al. Diagnostika a léčba hyperurikemie v kardiovaskulární prevenci na základě patofyziologického mechanismu jejího vzniku: expertní konsensus českých a slovenských odborníků 2024. AtheroRev. 2024; 9(2): 61–71.
7. Pascart T, Norberciak L, Ea H-K, et al. Patients with earlyonset gout and development of earlier severe joint involvement and metabolic comorbid conditions: Results from a cross-sectional epidemiologic survey. Arthritis Care Res. 2019; 71 : 986–992.
8. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res. (Hoboken) 2020; 72(6): 744–760.
9. Cipolletta E, Tata LJ, Abhishek A. Colchicine and cardiovascular protection in gout: unresolved questions – Authors’ reply. Lancet Rheumatol. 2025; 7(3): e161.
10. Sun M, Lyu Z, Wang C, et al. 2024 Update of Chinese Guidelines for Diagnosis and Treatment of Hyperuricemia and Gout Part I: Recommendations for General Patients. Int J Rheum Dis. 2025; 28(7): e70375.
11. Richette P, Doherty M, Pascual E, et al. 2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout. Ann Rheum Dis. 2020; 79(1): 31–38.
12. Hill EM, Sky K, Sit M, wt al. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol. 2015; 21(3): 120–125.
13. Mikuls TR, Cheetham TC, Levy GD, et al. Adherence and outcomes with urate-lowering therapy: A site-randomized trial. Am J Med. 2019; 132(3): 354–361.
14. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005; 353(23): 2450–2461. 15. White WB, Saag KG, Becker MA, et al.; CARES Investigators. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018; 378(13): 1200–1210.
16. Mackenzie IS, Ford I, Nuki G, et al.; FAST Study Group. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet 2020; 396(10264): 1745–1757.
17. Shin A, Choi SR, Han M, et al. Cardiovascular safety asso-ciated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat. Semin Arthritis Rheum. 2022; 56 : 152080.
18. Yang S, Hu Q, Liu K, et al. Serum uric acid reduction through SGLT2 inhibitors: evidence from a systematic review and meta-analysis. Front Pharmacol. 2025; 16 : 1551390.
19. Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007–2008. Am J Med. 2012; 125(7): 679–687.
20. Gaffo AL, Jacobs DR Jr, Sijtsma F, et al. Serum urate association with hypertension in young adults: analysis from the Coronary Artery Risk Development in Young Adults cohort. Ann Rheum Dis. 2013; 72(8): 1321–1327.
21. Zoccali C, Maio R, Mallamaci F, et al. Uric acid and endothelial dysfunction in essential hypertension. J Am Soc Nephrol. 2006; 17(5): 1466–1471.
22. Kuo CF, Yu KH, Luo SF, et al. Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study. Rheumatology (Oxford) 2010; 49(6): 1189–1896.
23. Kang DH, Park SK, Lee IK, et al. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol. 2005; 16(12): 3553–3562.
24. Moshkovits Y, Tiosano S, Kaplan A, et al. Serum uric acid sig-nificantly improves the accuracy of cardiovascular risk score models. Eur J Prev Cardiol. 2023; 30(7): 524–532.
25. Bredemeier M, Lopes LM, Eisenreich MA, et al. Xanthine oxida-se inhibitors for prevention of cardiovascular events: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2018; 18(1): 24.
26. Gill D, Cameron AC, Burgess S, et al. Urate, blood pressure, and cardiovascular disease: Evidence from mendelian randomization and meta-analysis of clinical trials. Hypertension 2021; 77(2): 383–392.
27. Mackenzie IS, Hawkey CJ, Ford I, et al.; ALL-HEART Study Group. Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. Lancet 2022; 400(10359): 1195–1205.
28. Long X, Wang Z, Yuan W. Effects of febuxostat on heart failure patients with asymptomatic hyperuricaemia: a retrospective cohort study. BMJ Open 2025; 15(7): e099442.
29. Kotozaki Y, Satoh M, Tanno K, et al. Plasma xanthine oxidore-ductase activity is associated with a high risk of cardiovascular disease in a general Japanese population. Int J Environ Res Public Health 2021; 18(4): 1894.
30. Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med. 2012; 125(7): 679–87.e1.
31. Hansildaar R, Vedder D, Baniaamam M, et al. Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout. Lancet Rheumatol. 2021; 3(1): e58–e70.
32. Ridker PM, Everett BM, Thuren T, et al.; CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017; 377(12): 1119–1131.
33. Cipolletta E, Tata LJ, Nakafero G, et al. Association between gout flare and subsequent cardiovascular events among patients with gout. JAMA 2022; 328(5): 440–450.
34. Lopez D, Dwivedi G, Nossent J, et al. Risk of major adverse cardiovascular event following incident hospitalization for acute gout: A western Australian population-level linked data study. ACR Open Rheumatol. 2023; 5(6): 298–304.
35. Hill EM, Sky K, Sit M, et al. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol. 2015; 21(3): 120–125.
36. Pavelka K. Doporučení České revmatologické společnosti pro léčbu dny. Čes. Revmatol. 2019; 27(4): 166–176.
37. Coburn BW, Mikuls TR. The problem with gout is that it’s still such a problem. J Rheumatol. 2016; 43(8): 1453–1455.
Labels
Dermatology & STDs Paediatric rheumatology RheumatologyArticle was published in
Czech Rheumatology
2025 Issue 3
Most read in this issue
- MUDr. Olga Kryštůfková, Ph.D
- Correction of hyperuricemia across stages of gout A rheumatologist‘s perspective – the debate continues
- Rheumatology care in the Czech Republic: A cross-sectional analysis of care providers in 2024
- EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer