Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul;8(2):e002348.
doi: 10.1136/rmdopen-2022-002348.

Urate crystal deposition is associated with inflammatory markers and carotid artery pathology in patients with intercritical gout: results from the NOR-Gout study

Hilde Berner Hammer  1   2 , Silvia Rollefstad  3 , Anne Grete Semb  3 , Gro Jensen  4 , Lars Fridtjof Karoliussen  5 , L Terslev  6 , Espen A Haavardsholm  5   2 , Tore K Kvien  5   2 , Till Uhlig  5   2
Affiliations

Urate crystal deposition is associated with inflammatory markers and carotid artery pathology in patients with intercritical gout: results from the NOR-Gout study

Hilde Berner Hammer et al. RMD Open. 2022 Jul.

Abstract

Background: Gout is of unknown reason associated with cardiovascular disease. Ultrasound is sensitive for detecting crystal deposition and plasma calprotectin is a sensitive inflammatory marker. This study explores the associations between crystal deposition, inflammation and carotid artery pathology.

Method: A cross-sectional analysis of baseline assessments from the NOR-Gout study was undertaken. Crystal deposition was assessed by ultrasound (double contour, tophi, aggregates) and dual-energy CT (DECT) and laboratory assessments included plasma calprotectin. The carotid arteries were bilaterally examined for carotid intima-media thickness (cIMT) and presence of plaques. Spearman correlations, Mann-Whitney tests and linear regression analyses were used to explore associations between crystal deposition, inflammatory markers,and carotid pathology.

Results: 202 patients with intercritical gout (95.5% men, mean (SD) age 56.5 (13.8) years, disease duration 7.9 (7.7) years) were included. Calprotectin was correlated with all scores of crystal deposition by ultrasound (r=0.26-0.32, p<0.001) and DECT (r=0.15, p<0.05). cIMT was correlated with sum score aggregates (r=0.18-0.22, p<0.05). Patients with large tophi had higher levels of calprotectin as well as more frequent carotid plaque (p<0.05).

Conclusions: Study findings point towards crystal deposition contributing to subclinical inflammation with subsequent vascular implications. However, future longitudinal studies are needed to confirm such causal relationships.

Keywords: Cardiovascular Diseases; Gout; Inflammation; Ultrasonography.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Dr. Hammer reports personal fees from AbbVie, Lilly, UCB and Novartis, outside the submitted work. Dr. Rollefstad has no disclosures. Msc Jensen has no disclosures.Dr. Karoliussen has no disclosures.Dr. Terslev reports personal fees from Novartis, Roche, BMS and Pfizer outside the submitted work.Dr. Haavardsholm reports personal fees from Pfizer, UCB, Eli Lilly, Celgene, Janssen-Cilag, AbbVie and Gilead outside the submitted work.Dr. Kvien reports grants and personal fees from AbbVie, MSD, UCB, Hospira/Pfizer, Eli-Lilly, grants from BMS, personal fees from Roche, Hikma, Orion, Sanofi, Celltrion, Sandoz, Biogen, Amgen, Egis, Ewopharma and Mylan, outside the submitted work.Dr. Semb has received speaker honoraria and/or consulting fee from Novartis, AbbVie, Sanofi, KPMG, Bayer and Lilly and a collaborative agreement for independent research from Eli Lilly outside the submitted work.Dr. Uhlig reports personal fees from Galapagos, Grünenthal, Novartis, Pfizer, SOBI and UCB outside the submitted work.

Figures

Figure 1
Figure 1
With elevated calprotectin levels had significantly higher crystal load (p<0.001) than patients with normal calprotectin levels.
See this image and copyright information in PMC

References

    1. Lim SY, Lu N, Oza A, et al. Trends in gout and rheumatoid arthritis hospitalizations in the United States, 1993-2011. JAMA 2016;315:2345–7. 10.1001/jama.2016.3517 - DOI - PMC - PubMed
    1. Cox P, Gupta S, Zhao SS, et al. The incidence and prevalence of cardiovascular diseases in gout: a systematic review and meta-analysis. Rheumatol Int 2021;41:1209–19. 10.1007/s00296-021-04876-6 - DOI - PMC - PubMed
    1. Clarson LE, Chandratre P, Hider SL, et al. Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis. Eur J Prev Cardiol 2015;22:335–43. 10.1177/2047487313514895 - DOI - PMC - PubMed
    1. Calabuig I, Martínez-Sanchis A, Andrés M. Sonographic tophi and inflammation are associated with carotid atheroma plaques in gout. Front Med 2021;8:795984. 10.3389/fmed.2021.795984 - DOI - PMC - PubMed
    1. Perez-Ruiz F, Martínez-Indart L, Carmona L, et al. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis 2014;73:177–82. 10.1136/annrheumdis-2012-202421 - DOI - PubMed