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. 2024 Jul 8;26(1):127.
doi: 10.1186/s13075-024-03360-3.

The Relationship between the complement system and subclinical carotid atherosclerosis in patients with rheumatoid arthritis

Marta Hernández-Díaz  1 , Dara Rodríguez-González  2 , Elena Heras-Recuero  3 , Fuensanta Gómez-Bernal  2 , Juan Carlos Quevedo-Abeledo  4 , Agustín F González-Rivero  2 , Elena González-López  5 , J Gonzalo Ocejo-Vinyals  5 , Alejandro Jimenez-Sosa  6 , Miguel Ángel González-Gay  7   8 , Iván Ferraz-Amaro  9   10
Affiliations

The Relationship between the complement system and subclinical carotid atherosclerosis in patients with rheumatoid arthritis

Marta Hernández-Díaz et al. Arthritis Res Ther. .

Abstract

Background: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) events and CV mortality. Subclinical carotid atherosclerosis is independently associated with rates of incident CV events among patients with RA. The complement system has been related to both the etiopathogenesis of RA and CV disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and carotid intima media thickness and carotid plaque in patients with RA.

Methods: 430 patients with RA were recruited. Functional assays of the three pathways of the complement system, utilizing new-generation techniques, were assessed. Additionally, serum levels of individual components of the complement system belonging to the three pathways were measured: C1q (classical), lectin (lectin), C2, C4, and C4b (classical and lectin), factor D and properdin (alternative), C3 and C3a (common), C5, C5a, and C9 (terminal), as well as regulators factor I and C1-inhibitor. Subclinical carotid atherosclerosis was evaluated by ultrasonography. Multivariable linear regression analysis was conducted to investigate the association between the complement system and carotid intima media thickness and carotid plaque.

Results: After multivariable adjustment, which included traditional CV risk factors and disease-related data, C3a and C5a exhibited significant positive correlations with carotid intima media thickness. Additionally, higher values of C1-inhibitor, properdin, C3, C5, and C5a were independently associated with the presence of carotid plaque.

Conclusion: The complement system and subclinical carotid atherosclerosis are linked in patients with RA.

Keywords: Atherosclerosis; Cardiovascular disease; Carotid plaque; Complement system; Intima media thickness; Rheumatoid arthritis.

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Conflict of interest statement

The authors declare that they have no competing interests related to this study. Nevertheless, Professor MA Gonzalez-Gay and Dr. Iván Ferraz-Amaro would like to acknowledge that they have received grants/research supports from Abbott, MSD, Jansen and Roche, as well as consultation fees from company-sponsored speakers bureaus associated with Abbott, Pfizer, Roche, Sanofi, Celgene and MSD.

Figures

Fig. 1
Fig. 1
Heatmap of the relationship between complement system and carotid ultrasound assessment. Values in the cells represent multivariable standardized beta coefficients of the association between complement system (independent variable) and carotid intima media thickness (A) and carotid plaque (B) (dependent variables). Model 1 is adjusted for demographics and traditional cardiovascular factors, and Model 2 for Model 1 + disease related data. CL: classical, LE: lectin, AL: alternative, fI: factor I, fD: factor D. Significant correlation and standardized beta coefficients with a p < 0.05 are depicted as *
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