OP0204 URATE CRYSTAL DEPOSITIONS ARE ASSOCIATED WITH INFLAMMATORY MARKERS AND CAROTID PLAQUES INDICATING SUBCLINICAL INFLAMMATION IN GOUT; BASELINE RESULTS FROM THE NOR-GOUT STUDY
Authors: H. B. Hammer, S. Rollefstad, G. Jensen, L. Karoliussen, L. Terslev, E. A. Haavardsholm, T. K. Kvien, A. G. Semb, T. Uhlig
Journal: Annals of the Rheumatic Diseases (2021)

Background: In gout patients the extent of monosodium urate (MSU) crystal depositions can be quantitated by use of ultrasound. Gout may be associated with atherosclerotic disease which might be related to low-grade inflammation. Calprotectin is a major granulocyte protein reflecting the level of systemic inflammation. Objectives: To explore whether the extent of MSU crystal depositions is associated with low grade systemic inflammation as assessed by calprotectin/C-reactive protein (CRP) and with carotid pathologies in asymptomatic gout patients. Methods: The baseline data from NOR-GOUT, a prospective study of patients with crystal-proven gout with increased serum urate levels (&gt;360 μmol/L), were used. All patients were assessed by ultrasound (GE Logiq E9 machine) to assess MSU depositions (OMERACT definitions; double contour (DC), tophi and aggregates) with bilateral assessment of wrist, MCP2, knee, ankle, MTP1 and insertions of triceps, quadriceps, proximal/distal patellar and Achilles tendons, all scored semi-quantitatively 0-3. Bilateral B-mode ultrasound assessments of the carotid arteries examined carotid intima-media thickness (cIMT; increased thickness &gt;0.9mm). Atherosclerotic plaques were identified as protrusions of ≥1.5 mm or ≥ 2 times the adjacent IMT. Sum scores of each of the ultrasound elementary lesions for MSU depositions were calculated and the associations with calprotectin (plasma assessed by ELISA (Calpro), normal levels &lt;910 µg/L), CRP (routine assessment, normal levels &lt;4mg/L) as well as cIMT and presence of carotid plaque were explored. Correlations were performed by use of Spearman and differences between group was investigated by Mann-Whitney test. Results: A total of 202 gout patients without flare were included (95.5% men, mean (SD) age of 56.5 (13.8) years, 7.9 (7.7) years since first flare). The mean (SD) sum sore of DC was 4.4 (3.5), tophi 6.6 (6.6), aggregates 9.3 (5.6), calprotectin 801 (525) µg/L, CRP 7 (14) mg/L and serum urate (SUA) 499 (77) μmol/L. Carotid examinations were performed in 122 (60.4%) of the patients. Significant correlations were found between the MSU depositions and the inflammatory markers as well as cIMT. The 27% patients with increased calprotectin had the highest levels of each of the three elementary lesions (p=0.001) (Figure), and the 39% with elevated CRP levels had the highest levels of tophi and aggregates (p&lt;0.05). The 18% with increased thickness of cIMT and the 53% of patients with carotid plaque had the highest levels of aggregates (p=0.003 and p=0.037, respectively). Conclusion: In asymptomatic gout patients, higher load of MSU crystal depositions was associated with increased levels of inflammatory markers, cIMT and presence of atherosclerotic plaques in the carotid arteries. This may indicate that crystal depositions cause subclinical inflammation with subsequent systemic implications, but future longitudinal studies are needed to confirm such causal relationships. Sum score double contour Sum score tophi Sum score aggregates Calprotectin 0.26** 0.32** 0.28** CRP 0.20* 0.25** 0.18* Right IMT NS NS 0.18* Left IMT NS NS 0.21* Sum bilateral IMT NS NS 0.22* Spearman’s correlations. NS; Not significant, *p&lt;0.05, **p&lt;0.001 Disclosure of Interests: Hilde Berner Hammer Speakers bureau: AbbVie, Lilly and Novartis, Silvia Rollefstad: None declared, Gro Jensen: None declared, Lars Karoliussen: None declared, Lene Terslev Speakers bureau: Speakers fee from AbbVie, Janssen, Roche, Novartis, Pfizer, MSD, BMS and GE, Espen A Haavardsholm: None declared, Tore K. Kvien Speakers bureau: Tore K Kvien has received fees for speaking and/or consulting and/or research funding to Diakonhjemmet Hospital from AbbVie, Biogen, BMS, Celltrion, Egis, Evapharma, Ewopharma, Eli Lilly, Gilead, Hikma, MSD, Mylan, Novartis, Oktal, Pfizer, Sandoz, Sanofi and UCB., Anne Grete Semb: None declared, Till Uhlig: None declared