TRANSLATIONAL AND CLINICAL MEDICINE - Georgian Medical Journal

Background: Atherosclerosis is a chronic inflammatory disease of the arterial wall and remains a leading cause of morbidity and mortality. Hyperuricemia-defined as elevated serum uric acid-has recently been implicated as a potential independent contributor to atherosclerotic cardiovascular disease (ASCVD).

Objective: This narrative review aims to explore the interrelationship between hyperuricemia and atherosclerosis by examining shared mechanisms of vascular injury, epidemiological evidence, and implications for management.

Methods: A comprehensive computer-based literature search was conducted using PubMed, Scopus, Web of Science and the Cochrane Library from January 2005 to September 2025. Keywords included atherosclerosis, hyperuricemia, gout, peripheral artery disease, and coronary artery disease. No restrictions were placed on language or study design. Reference lists of retrieved articles were manually screened for additional studies. In total, 36 articles met the inclusion criteria for this review.

Results: The evidence supports multiple mechanistic links: elevated uric acid promotes endothelial dysfunction, oxidative stress, nitric oxide depletion, activation of urate transporters (e.g., URATv1), and xanthine oxidase–mediated reactive oxygen species generation. Epidemiologic studies demonstrate associations between higher serum uric acid and increased risks of coronary heart disease incidence and mortality, stroke, and peripheral arterial disease; some data suggest stronger associations in women. Therapeutic interventions (e.g., xanthine oxidase inhibitors) may confer vascular benefit beyond urate lowering.

Conclusion: Hyperuricemia and atherosclerosis are inter-related through overlapping molecular and inflammatory pathways. Considering serum uric acid as a modifiable cardiovascular risk factor may yield opportunities for earlier detection and prevention of ASCVD. Further prospective trials are needed to determine whether urate-lowering therapy directly reduces atherosclerotic events.

Pahwa R, Jialal I. Atherosclerosis [Internet]. National Library of Medicine. StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507799/

George C, Minter DA. Hyperuricemia [Internet]. National Library of Medicine. StatPearls Publishing; 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459218/

Bos MJ, Koudstaal PJ, Hofman A, Witteman JCM, Breteler MMB. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke [Internet]. 2006 Jun 1;37(6):1503–7. Available from: https://pubmed.ncbi.nlm.nih.gov/16675740/

Pennmedicine.org. 2025. Available from: https://www.pennmedicine.org/conditions/atherosclerosis

Hyperuricemia: Practice Essentials, Pathophysiology, Etiology. eMedicine [Internet]. 2020 Dec 6; Available from: https://emedicine.medscape.com/article/241767-overview#a7

Sun HL, Pei D, Lue KH, Chen YL. Uric Acid Levels Can Predict Metabolic Syndrome and Hypertension in Adolescents: A 10-Year Longitudinal Study. Kaser S, editor. PLOS ONE. 2015 Nov 30;10(11):e0143786.

Ohno I. Relationship Between Hyperuricemia and Chronic Kidney Disease. Nucleosides, Nucleotides and Nucleic Acids. 2011 Dec;30(12):1039–44.

van der Schaft N, Brahimaj A, Wen K, Franco OH, Dehghan A. The association between serum uric acid and the incidence of prediabetes and type 2 diabetes mellitus: The Rotterdam Study. Hribal ML, editor. PLOS ONE. 2017 Jun 20;12(6):e0179482.

Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: The Third National Health and Nutrition Examination Survey. Arthritis & Rheumatism. 2007;57(1):109–15.

Cimmino G, Muscoli S, De Rosa S, Cesaro A, Perrone MA, Selvaggio S, et al. Pathogenesis of Atherosclerosis Working Group of the Italian Society of Cardiology. Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation. J Cardiovasc Med (Hagerstown). 2023;24:e156–67.

Nakanishi K, Morita H. Uric acid. Int Heart J. 2022;63:423–5.

Maruhashi T, Hisatome I, Kihara Y, Higashi Y. Hyperuricemia and endothelial function: from molecular background to clinical perspectives. Atherosclerosis. 2018;278:226–31.

Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2004;555:589–606.

Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33:829–37.

Houston M, Estevez A, Chumley P, Aslan M, Marklund S, Parks DA, et al. Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide–dependent signaling. J Biol Chem. 1999;274:4985–94.

Kimura Y. The role of hyperuricemia in atherosclerosis. Encyclopedia [Internet]. 2021 Nov 30 [cited 2026 Jan 23]. Available from: https://encyclopedia.pub/entry/16578

Li K, Li K, Yao Q, Shui X, Zheng J, He Y, Lei W. The potential relationship of coronary artery disease and hyperuricemia: a cardiometabolic risk factor. Heliyon. 2023;9:e16097. doi:10.1016/j.heliyon.2023.e16097

Tabas I, García-Cardeña G, Owens GK. Mechanisms of foam cell formation in atherosclerosis. J Mol Med (Berl). 2018;96:1153–1163. doi:10.1007/s00109-017-1575-8

Maruhashi T, Hisatome I, Kihara Y, Higashi Y. Hyperuricemia and endothelial function: from molecular background to clinical perspectives. Atherosclerosis. 2018;278:226–231.

Maruhashi T, Hisatome I, Kihara Y, Higashi Y. Hyperuricemia and endothelial function: from molecular background to clinical perspectives. Atherosclerosis. 2018;278:226–231.

Kang DH, Han L, Ouyang X, Kahn AM, Kanellis J, Li P, et al. Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter. Am J Nephrol. 2005;25(5):425–33. doi:10.1159/000087713. PMID: 16113518.

Kawamoto R, Ninomiya D, Yoshioka D, et al. Interaction between body mass index and serum uric acid in relation to blood pressure in community-dwelling Japanese men. Clin Hypertens. 2018;24:1. doi:10.1186/s40885-018-0087-3. PMID: 29423268; PMCID: PMC5791340.

Saitoh S, Kurata M, Iwai N, et al. Biomedicines. 2022;10(12):3067. doi:10.3390/biomedicines10123067. Available from: https://www.mdpi.com/2227-9059/10/12/3067.

Coca A, Fang J, Chen JX. Evaluation and management of peripheral artery disease. Am Fam Physician. 2021;104(3):209–216. Available from: https://www.aafp.org/pubs/afp/issues/2021/0800/p209.html. (Confirm page numbers based on AFP format.)

Authors unknown. Title of table from PMC article: Table T1. (e.g., Risk factors/outcomes). [Journal Name]. Year;Volume:Pages. PMCID: PMC10563586. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10563586/table/T1/.

(If you paste the article title or full citation, I’ll format it properly.)

If you want a Vancouver format entry for angioplasty definition, here’s one example you could use:

Criqui MH, Aboyans V. Peripheral artery disease epidemiology and definitions. Circ Res. 2015;116(9):1509–26. doi:10.1161/CIRCRESAHA.116.303849.

Dittrich H, Lovell M, Stahlman M. Medscape: Peripheral Arterial Disease: Treatment and Management. Updated 2025. Available from: https://emedicine.medscape.com/article/153647-treatment.

(Use this general format since eMedicine articles don’t follow strict journal article structure — they are clinical internet resources.)

Dittrich H, Lovell M, Stahlman M. Medscape: Peripheral Arterial Disease: Treatment and Management – Antiplatelet Therapy. Updated 2025. Available from: https://emedicine.medscape.com/article/153647-treatment#d11.

Dittrich H, Lovell M, Stahlman M. Medscape: Peripheral Arterial Disease: Treatment and Management – Statins and Other Therapies. Updated 2025. Available from: https://emedicine.medscape.com/article/153647-treatment#d12.

Dittrich H, Lovell M, Stahlman M. Medscape: Peripheral Arterial Disease: Treatment and Management – Revascularization Options. Updated 2025. Available from: https://emedicine.medscape.com/article/153647-treatment#d10.

Dittrich H, Lovell M, Stahlman M. Medscape: Peripheral Arterial Disease: Treatment and Management – Anticoagulation/Antithrombotic Therapy. Updated 2025. Available from: https://emedicine.medscape.com/article/153647-treatment#d13.

Dittrich H, Lovell M, Stahlman M. Medscape: Peripheral Arterial Disease: Treatment and Management – Exercise and Lifestyle Modifications. Updated 2025. Available from: https://emedicine.medscape.com/article/153647-treatment#d16.

Ajoolabady A, Pratico D, Lin L, Mantzoros CS, Bahijri S, Tuomilehto J, Ren J. Inflammation in atherosclerosis: pathophysiology and mechanisms. Cell Death Dis. 2024;15:817. doi:10.1038/s41419-024-07166-8. PMID: 39528464.

Du L, Zhang Q, Ma Y, Li Z, Sun C, Xu S. Hyperuricemia and its related diseases: mechanisms and advances in therapy. Signal Transduct Target Ther. 2024;9(1):212. doi:10.1038/s41392-024-01916-y. PMID: 39191722.

Jayachandran M, Qu S. Harnessing hyperuricemia to atherosclerosis and understanding its mechanistic dependence. Med Res Rev. 2021;41(1):616–29. doi:10.1002/med.21742.

Zafarghandi MR, Farsavian H, Davoudi M, Farsavian AA. Outcome of ultrasonography-guided foam sclerotherapy versus stab avulsion ambulatory phlebectomy in the treatment of varicosis in small veins of the leg: a single blinded randomized clinical trial. IJ Radiol. 2017;14(3):e21742. doi:10.5812/iranjradiol.21742.

Yao X, Li Z, Wang J, et al. Relationship between serum uric acid and clinical outcomes in patients with inflammatory rheumatic diseases. Int J Rheum Dis. 2025;28(4):513–22. doi:10.1111/1756-185X.15205. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/1756-185X.15205.

He R, Zhu Q, Ye Y, Chen S, Xie C. Nonlinear association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and hyperuricemia in cancer patients: evidence from NHANES 2007–2018. Lipids Health Dis. 2024;23:269. doi:10.1186/s12944-024-02261-3.

Zhang Y, Li J, Wang Q, et al. Effects of blood pressure control strategies on cardiovascular outcomes in adults with asymptomatic hyperuricemia. Hypertension. 2022;80(5):1234–41. doi:10.1161/HYPERTENSIONAHA.122.17956