Hyperuricemia and inflammation in chronic inflammatory arthritis: A post-hoc analysis of the CARMA project
Antonio Avilés (1,2) , Zulema Plaza (3) , Fernando Sánchez-Alonso (3) , Santos Castañeda (4), Benjamín Fernández (5) , César Díaz (6) , Pilar Font (7), Olga Martínez (8) , Emilio Giner (9), José Miguel Senabre (10) , Amalia Rueda (11) , Ana Pérez (12) , Gines Sanchez (13 , Carlos González (14), Javier García (15) , Javier Llorca (16), Miguel Ángel González-Gay (16,17) , Mariano Andrés (1,2,18).
Affiliation(s):
1. hospital General Universitario Dr. Balmis, Alicante.
2. Instituto De Investigación Sanitaria Y Biomédica De Alicante (isabial).
3. unidad De Investigación De La Sociedad Española De Reumatología, Madrid,
4. hospital Universitario La Princesa, Iis-princesa, Madrid.
5. Hospital Clínico Universitario San Carlos, Madrid.
6. hospital De La Santa Creu I Sant Pau, Barcelona.
7. hospital Universitario Reina Sofía, Córdoba.
8. hospital Clínico Universitario De Salamanca.
9. hospital General Obispo Polanco, Teruel.
10. hospital Marina Baixa, Alicante.
11. hospital General Universitario De Valencia, Valencia.
12. hospital Universitario Príncipe De Asturias, Madrid.
13. hospital General De Albacete.
14. hospital Universitario 12 De Octubre, Madrid.
15. hospital Universitario Lucus Augusti, Lugo.
16. universidad De Cantabria, Santander.
17. Iis Fundación Jiménez Diaz, Madrid.
18. universidad Miguel Hernández, Elche. Spain.
Background : Hyperuricemia is associated with a basal pro-inflammatory state, although during acute inflammatory episodes, such as gout attacks, blood serum urate (SU) levels may decrease. This relationship has not been thoroughly investigated in chronic inflammatory arthritis (CIAs) such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). These diseases are characterized by chronic inflammation, but the specific impact of hyperuricemia on their activity and progression remains uncertain. This study examines the association between SU levels, inflammatory markers, and disease activity index in CIAs, seeking to elucidate potential pathophysiological interactions.
Methods : A post-hoc analysis of the CARMA project, a 10-year prospective study on cardiovascular events in patients with CIAs (RA, AS, PsA) and controls with non-inflammatory rheumatisms (osteoarthritis, osteoporosis, soft tissue injuries) recruited from 67 Spanish hospitals between 2010 and 2022, was conducted. Hyperuricemia was defined as SU >6.8 mg/dL. SU levels, C-reactive protein (CRP), and Erythrocyte Sedimentation Rate (ESR) were analyzed, expressed as median and interquartile range due to their non-normal distribution. The Mann-Whitney U test compared CRP and ESR levels between normouricemic and hyperuricemic individuals in each pathology and controls. The correlation between SU-CRP and SU-ESR was evaluated using Pearson's coefficient. Specific activity index (DAS28 for RA and PsA; BASDAI for AS) were also calculated, and DAS28-CRP components (number of swollen joints [SJC], tender joints [TJC], acute phase reactants [APR], and patient global assessment [VAS]) were analyzed.
Results : Of 1552 patients with CIAs, 174 (11.2%) were hyperuricemic: 39 (6.9%) with RA, 78 (15.5%) with AS, and 57 (11.8%) with PsA. Mean SU levels were 5.0 ± 2.3 mg/dL in CIAs (4.6 ± 3.1 in RA; 5.3 ± 1.5 in AS; 5.1 ± 2.0 in PsA) and 5.0 ± 1.4 mg/dL in controls, with 11.2% classified as hyperuricemic. CRP levels were significantly higher in hyperuricemic patients with AS (p=0.002), PsA (p=0.038), and controls (p<0.001), but not in RA (p=0.162). There were no significant differences in erythrocyte sedimentation rate (ESR) between normo- and hyperuricemic individuals in any of the groups studied.
The correlation between SU and CRP was not significant for RA (r=+0.1), AS (r=+0.03), or PsA (r=+0.17), but was moderate in controls (r=+0.43). No correlation was found between SU and ESR in any group studied. Regarding activity index, there were no significant differences between normo- and hyperuricemic individuals for DAS28 in RA (p=0.428) or PsA (p=0.659), nor for BASDAI in AS (p=0.9216). DAS28 components also showed no significant correlation with SU.
Conclusion : This study reveals a complex relationship between hyperuricemia and inflammation in CIAs. Although elevated CRP levels were associated with hyperuricemia in AS, PsA, and controls, this relationship did not extend to other markers such as ESR or activity index like DAS28 or BASDAI. These findings suggest that the interaction between hyperuricemia and inflammation varies according to the specific pathology, highlighting the need for additional research to better understand its clinical and pathophysiological implications within the context of chronic inflammatory arthritis.
