Hyperuricemia and Cardiovascular Disease: Mechanisms, Associations, and Therapeutic Implications – A Literature Review
DOI:
https://doi.org/10.12775/QS.2025.45.66515Keywords
uric acid, hyperuricemia, cardiovascular diseaseAbstract
Uric acid has emerged as a potential biomarker for cardiovascular risk. Hyperuricemia, described as an abnormally elevated concentration of uric acid in the bloodstream, has been associated with the development of cardiovascular diseases such as hypertension, atrial fibrillation, heart failure, and coronary heart disease. Recent studies have investigated the potential benefits of using uric acid-lowering therapy in slowing the progression of these diseases. In this review, we summarize current evidence on the impact of hyperuricemia on cardiovascular diseases and the effectiveness of urate-lowering therapy in affected patients.
References
1. Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V. Regulation of uric acid metabolism and excretion. Int J Cardiol 2016; 213: 8–14.
2. Jin M, Yang F, Yang I et al. Uric acid, hyperuricemia and vascular diseases. Frontiers in Bioscience 2012; 17: 656–669.
3. So A, Thorens B. Uric acid transport and disease. J Clin Invest 2010; 120: 1791–1799.
4. Glynn RJ, Campion EW, Silbert JE. Trends in serum uric acid levels. Arthritis Rheum 1983; 26: 87–93.
5. Li R, Yu K, Li C. Dietary factors and risk of gout and hyperuricemia: A meta-analysis and systematic review. Asia Pac J Clin Nutr 2018; 27: 1344–1356.
6. Dalbeth N, Merriman TR, Stamp LK. Gout. The Lancet 2016; 388: 2039–2052.
7. Zhao G, Huang L, Song M, Song Y. Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: A meta-analysis of prospective studies. Atherosclerosis 2013; 231: 61–68.
8. Kuwabara M, Kuwabara R, Hisatome I et al. ‘Metabolically Healthy’ Obesity and Hyperuricemia Increase Risk for Hypertension and Diabetes: 5-year Japanese Cohort Study. Obesity 2017; 25: 1997–2008.
9. Kuwabara M, Niwa K, Nishihara S et al. Hyperuricemia is an independent competing risk factor for atrial fibrillation. Int J Cardiol 2017; 231: 137–142.
10. Culleton BF, Larson MG, Kannel WB, Levy D. Serum Uric Acid and Risk for Cardiovascular Disease and Death: The Framingham Heart Study. https://doi.org/107326/0003-4819-131-1-199907060-00003 2000; 131: 7–13.
11. Maruhashi T, Hisatome I, Kihara Y, Higashi Y. Hyperuricemia and endothelial function: From molecular background to clinical perspectives. Atherosclerosis 2018; 278: 226–231.
12. Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: A hypothesis. Proc Natl Acad Sci U S A 1981; 78: 6858–6862.
13. Papežíková I, Pekarová M, Kolářová H et al. Uric acid modulates vascular endothelial function through the down regulation of nitric oxide production. Free Radic Res 2013; 47: 82–88.
14. Kanellis J, Kang DH. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol 2005; 25: 39–42.
15. Abeles AM. Hyperuricemia, Gout, and Cardiovascular Disease: An Update. Curr Rheumatol Rep 2015; 17: 1–5.
16. Kuwabara M, Hisatome I, Niwa K et al. Uric Acid Is a Strong Risk Marker for Developing Hypertension from Prehypertension:A 5-Year Japanese Cohort Study. Hypertension 2018; 71: 78–86.
17. Scheepers LEJM, Boonen A, Dagnelie PC et al. Uric acid and blood pressure: Exploring the role of uric acid production in the Maastricht Study. J Hypertens 2017; 35: 1968–1975.
18. Miyabayashi I, Mori S, Satoh A et al. Uric Acid and Prevalence of Hypertension in a General Population of Japanese: ISSA-CKD Study. J Clin Med Res 2020; 12: 431–435.
19. Sundström J, Sullivan L, D’Agostino RB, Levy D, Kannel WB, Vasan RS. Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 2005; 45: 28–33.
20. Colmenares-Mejia CC, Quintero-Lesmes DC, Bautista-Niño PK et al. Uric acid and risk of pre-eclampsia: results from a large case–control study and meta-analysis of prospective studies. Sci Rep 2023; 13: 3018.
21. Gruszka K, Drożdż T, Wojciechowska W et al. Effects of uric acid-lowering therapy in patients with essential arterial hypertension. Blood Press Monit 2022; 27: 152–160.
22. Gaffo AL, Calhoun DA, Rahn EJ et al. Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial. Arthritis and Rheumatology 2021; 73: 1514–1522.
23. Carnes CA, Chung MK, Nakayama T et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res 2001; 89.
24. Nyrnes A, Toft I, Njølstad I et al. Uric acid is associated with future atrial fibrillation: An 11-year follow-up of 6308 men and women - the Tromsø study. Europace 2014; 16: 320–326.
25. Li S, Cheng J, Cui L et al. Cohort study of repeated measurements of serum urate and risk of incident atrial fibrillation. J Am Heart Assoc 2019; 8.
26. Singh JA, Yu S. Allopurinol and the risk of atrial fibrillation in the elderly: A study using medicare data. Ann Rheum Dis 2017; 76: 72–78.
27. Yu W, Cheng JD. Uric Acid and Cardiovascular Disease: An Update From Molecular Mechanism to Clinical Perspective. Front Pharmacol 2020; 11: 582680.
28. Tian X, Chen S, Zhang Y et al. An early accumulation of serum uric acid confers more risk of heart failure: a 10-year prospective cohort study. Eur Heart J Qual Care Clin Outcomes 2024; 11.
29. Gu J, Fan YQ, Zhang HL, Zhang JF, Wang CQ. Serum uric acid is associated with incidence of heart failure with preserved ejection fraction and cardiovascular events in patients with arterial hypertension. J Clin Hypertens 2018; 20: 560–567.
30. Huang H, Huang B, Li Y et al. Uric acid and risk of heart failure: a systematic review and meta-analysis. Eur J Heart Fail 2014; 16: 15–24.
31 EFFECTS OF HIGH DOSES OF ALLOPURINOL ON SERUM URIC ACID AND CARDIAC BIOMARKERS IN CHRONIC HEART FAILURE – Farmacia Journal. 2015, Vol. 63, 4
32. Givertz MM, Anstrom KJ, Redfield MM et al. Effects of xanthine oxidase inhibition in hyperuricemic heart failure patients: The xanthine oxidase inhibition for hyperuricemic heart failure patients (EXACT-HF) study. Circulation 2015; 131: 1763–1771.
33. Kanbay M, Afsar B, Siriopol D et al. Effect of Uric Acid-Lowering Agents on Cardiovascular Outcome in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Clinical Studies. Angiology 2020; 71: 315–323.
34. Braga F, Pasqualetti S, Ferraro S, Panteghini M. Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: A systematic review and meta-analysis. Clin Chem Lab Med 2016; 54: 7–15.
35. Zhang S, Liu X, Song B, Yu H, Zhang X, Shao Y. Impact of serum uric acid levels on the clinical prognosis and severity of coronary artery disease in patients with acute coronary syndrome and hypertension after percutaneous coronary intervention: A prospective cohort study. BMJ Open 2022; 12.
36. Ekici B, Kütük U, Alhan A, Töre HF. The relationship between serum uric acid levels and angiographic severity of coronary heart disease. Polish Heart Journal (Kardiologia Polska) 2015; 73: 533–538.
37. Zuo T, Liu X, Jiang L, Mao S, Yin X, Guo L. Hyperuricemia and coronary heart disease mortality: A meta-analysis of prospective cohort studies. BMC Cardiovasc Disord 2016; 16.
38. Li M, Hu X, Fan Y et al. Hyperuricemia and the risk for coronary heart disease morbidity and mortality a systematic review and dose-response meta-analysis. Sci Rep 2016;
39. Mackenzie IS, Hawkey CJ, Ford I et al. Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation. Health Technol Assess (Rockv) 2024; 28.
40. White WB, Saag KG, Becker MA et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. New England Journal of Medicine 2018; 378: 1200–1210.
41. Doehner W, Anker SD, Butler J et al. Uric Acid and SGLT2 Inhibition With Empagliflozin in Heart Failure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial. JACC Heart Fail 2024; 12.
42. Doehner W, Anker SD, Butler J et al. Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: The EMPEROR-reduced trial. Eur Heart J 2022; 43: 3435–3446.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Maciej Borowski, Michał Szczepański, Natalia Dzieszko, Weronika Kalinowska, Paulina Sara Kulasza, Aleksandra Szeliga, Tomasz Karol Książek, Kinga Kozłowska, Piotr Mikołaj Dembicki, Anna Ewelina Francuziak

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 129
Number of citations: 0