Asymptomatic hyperuricemia and gout: Are there any differences (data from a pilot case-control study)

Asymptomatic hyperuricemia (AH) and gout are characterized by the presence of elevated uric acid (UA) levels. It is not known whether there are differences between these conditions, beyond the acute attacks of arthritis unique to gout.

The aim – to identify differences in the frequency of concomitant diseases, metabolic disorders and dietary habits in patients with gout and asymptomatic hyperuricemia.

Material and methods. A single-stage observational case-control study included 202 people: 101 patients each with AH and gout, matched by age and gender. The examination included collection of anamnesis and medical documentation data on the presence of cardiovascular diseases, type 2 diabetes mellitus (T2DM), nephrolithiasis; inspection and measurement of anthropometric data. The intake of medications was recorded. A survey was conducted regarding the frequency of consumption of meat, seafood and alcohol. Blood levels of glucose, sUA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), creatinine, cholesterol, C-reactive protein (CRP), and ESR according to Westergren were determined. GFR was calculated using the CKD-EPI formula. All patients underwent ultrasound examination of the knee joints to determine signs of synovitis and deposition of monosodium urate (MSU) crystals.

Result. In patients with gout, arterial hypertension (86 (85.1%) vs 53 (52.4%) patients, respectively; p<0.05), T2DM (12 (11.9%) vs 4 (4.0%) patients, respectively; p<0.05) were detected more often than in patients with AH. In the gout group, there were more patients consuming alcohol ≥1 time per week (p=0.02), while there were no differences in the frequency of consumption of meat and seafood. Among patients with gout, there were more participants with GFR<60 ml/min/1.73 m². In patients with gout, there was a significant direct correlation between the levels of UA and ALT, creatinine, CRP, and an inverse correlation between serum UA and GFR. Ultrasound of the knee joints showed a significantly more frequent deposition of MSU crystals (46 (45.5%) vs 17 (16.8%) patients, respectively; p<0.05) and the presence of synovitis (37 (36.6%) vs 14 (13.8%) patients, respectively; p<0.05) in the gout group.

Conclusions. Despite the apparent commonality of gout and AH, they have a number of differences. In gout, arterial hypertension and T2DM are more often detected. Also, in patients with gout, there is a significant direct correlation between the levels of sUA and ALT, creatinine, CRP, while GFR is inversely correlated with the level of serum sUA. Among patients with AH, such correlations were not found. Gout also predicts a statistically more frequent detection of MSU crystal deposits (45.5% vs 31.1% of patients). The intake of meat and fish products did not differ in both groups.

1. Dalbeth N, Phipps-Green A, Frampton C, Neogi T, Taylor WJ, Merriman TR. Relationship between serum urate concentration and clinically evident incident gout: An individual participant data analysis. Ann Rheum Dis. 2018;77(7):1048-1052. doi: 10.1136/annrheumdis-2017-212288

2. Perez-Ruiz F, Dalbeth N, Bardin T. A review of uric acid, crystal deposition disease, and gout. Adv Ther. 2015;32(1):31-41. doi: 10.1007/s12325-014-0175-z

3. Liu S, Liu Y, Wu X, Liu Z. Metabolomic analysis for asymptomatic hyperuricemia and gout based on a combination of dried blood spot sampling and mass spectrometry technology. J Orthop Surg Res. 2023;18(1):769. doi: 10.1186/s13018-023-04240-3

4. Shalnova SA, Deev AD, Artamonov GV, Duplyakov DV, Efanov AYu, Zhernakova YuV, et al. Hyperuricemia and its correlates in the Russian population (results of ESSE-RF epidemiological study). Rational Pharmacotherapy in Cardiology. 2014;10(2):153-159 (In Russ.). doi: 10.20996/1819-6446-2014-10-2-153-159

5. Eliseev MS, Barskova VG. Metabolic syndrome in gout. Bulletin of the Russian Academy of Medical Sciences. 2008;6:26-32 (In Russ.).

6. Del Pinto R, Viazzi F, Pontremoli R, Ferri C, Carubbi F, Russo E. The URRAH study. Panminerva Med. 2021;63(4):416-423. doi: 10.23736/S0031-0808.21.04357-3

7. Kuo CF, See LC, Luo SF, Ko YS, Lin YS, Hwang JS, et al. Gout: An independent risk factor for all-cause and cardiovascular mortality. Rheumatology (Oxford). 2010;49(1):141-146. doi: 10.1093/rheumatology/kep364

8. Liang J, Jiang Y, Huang Y, Song W, Li X, Huang Y, et al. The comparison of dyslipidemia and serum uric acid in patients with gout and asymptomatic hyperuricemia: A cross-sectional study. Lipids Health Dis. 2020;19(1):31. doi: 10.1186/s12944-020-1197-y

9. Liu S, Sun H, Yang S, Liang N, Gao Y, Qu S, et al. Clustering of gout-related comorbidities and their relationship with gout flares: A data-driven cluster analysis of eight comorbidities. J Endocrinol Invest. 2024;47(5):1119-1128. doi: 10.1007/s40618-023-02224-y

10. Bursill D, Taylor WJ, Terkeltaub R, Abhishek A, So AK, Vargas-Santos AB, et al. Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout. Ann Rheum Dis. 2019;78(11):1592-1600. doi: 10.1136/annrheumdis-2019-215933

11. Liu W, Song H, Man S, Li H, Gao S. Simple metabolic markers associated with tophaceous gout. Clin Rheumatol. 2021;40(12):5047-5053. doi: 10.1007/s10067-021-05861-x

12. Nian YL, You CG. Susceptibility genes of hyperuricemia and gout. Hereditas. 2022;159(1):30. doi: 10.1186/s41065-022-00243-y

13. Choi HK, Mount DB, Reginato AM; American College of Physicians; American Physiological Society. Pathogenesis of gout. Ann Intern Med. 2005;143(7):499-516. doi: 10.7326/0003-4819-143-7-200510040-00009

14. Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015;17(1):98. doi: 10.1186/s13075-015-0609-2

15. Yang Q, Köttgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet. 2010;3(6):523-530. doi: 10.1161/CIRCGENETICS.109.934455

16. Pei L, Xie L, Wu J, Zhang H, Zhang X. Study on the relationship between FFA and gout flare. Clin Rheumatol. 2020;39(4):1251-1255. doi: 10.1007/s10067-019-04903-9

17. Kuo CF, Luo SF. Gout: Risk of premature death in gout unchanged for years. Nat Rev Rheumatol. 2017;13(4):200-201. doi: 10.1038/nrrheum.2017.27

18. Maloberti A, Mengozzi A, Russo E, Cicero AFG, Angeli F, Agabiti Rosei E, et al.; Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA). The results of the URRAH (Uric Acid Right for Heart Health) project: A focus on hyperuricemia in relation to cardiovascular and kidney disease and its role in metabolic dysregulation. High Blood Press Cardiovasc Prev. 2023;30(5):411-425. doi: 10.1007/s40292-023-00602-4

19. Ghasemi A. Uric acid-induced pancreatic β-cell dysfunction. BMC Endocr Disord. 2021;21(1):24. doi: 10.1186/s12902-021-00698-6

20. Zheliabina OV, Eliseev MS, Glukhova SI, Nasonov EL. Contributing factors of diabetes mellitus among patients with gout (results of the long-term prospective study). Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2022;60(3):374-380 (In Russ.). doi: 10.47360/1995-4484-2022-374-380

21. Cicero AFG, Fogacci F, Giovannini M, Grandi E, Rosticci M, D’Addato S, et al. Serum uric acid predicts incident metabolic syndrome in the elderly in an analysis of the Brisighella Heart Study. Sci Rep. 2018;8(1):11529. doi: 10.1038/s41598-018-29955-w

22. Hernández-Cuevas CB, Roque LH, Huerta-Sil G, Rojas-Serrano J, Escudero A, Perez LL, et al. First acute gout attacks commonly precede features of the metabolic syndrome. J Clin Rheumatol. 2009;15(2):65-67. doi: 10.1097/RHU.0b013e31819c0dba

23. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Comorbidities in patients with gout prior to and following diagnosis: Case-control study. Ann Rheum Dis. 2016;75(1):210-217. doi: 10.1136/annrheumdis-2014-206410

24. Cheremushkina EV, Eliseev MS. Hyperuricemia and gout: Effects on bone and articular cartilage (literature review). Obesity and Metabolism. 2022;19(3):348-357 (In Russ.). doi: 10.14341/omet12894

25. Sah SK, Khatiwada S, Pandey S, Kc R, Das BK, Baral N, et al. Association of high-sensitivity C-reactive protein and uric acid with the metabolic syndrome components. Springerplus. 2016;5:269. doi: 10.1186/s40064-016-1933-y

26. Lawler PR, Bhatt DL, Godoy LC, Lüscher TF, Bonow RO, Verma S, et al. Targeting cardiovascular inflammation: Next steps in clinical translation. Eur Heart J. 2021;42(1):113-131. doi: 10.1093/eurheartj/ehaa099

27. Rodnan GP. The pathogenesis of aldermanic gout: Procatarctic role of fluctuations in serum urate concentration in gouty arthritis provoked by feast and alcohol. Arthritis Rheum. 1980;23(Suppl):737.

28. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: A prospective study. Lancet. 2004;363(9417):1277-1281. doi: 10.1016/S0140-6736(04)16000-5