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Introduction: Increasing scientific evidence suggests that systemic inflammatory diseases play a central role in the development of arteriosclerosis [1]. To better understand the pathogenesis, it is important to investigate which additional risk factors could contribute to atherosclerosis [2]. In recent years, various candidate genes, genetic polymorphisms and susceptibility loci have been identified that are associated with atherosclerotic diseases [3]. This study aimed to evaluate genetic and clinical predictors of carotid intima media thickness (cIMT) in patients with rheumatoid arthritis (RA).

Methods: Out of a cohort of 133 RA patients, we studied typical arteriosclerosis risk factors (age, sex, body-mass-Index (BMI), lipid status, diabetes mellitus, and hypertension) as well as RA disease activity compared to 33 hand osteoarthritis (OA) patients. To evaluate arteriosclerosis, ultrasound examination of brain supplying arteries for determination of plaques was performed, as well as the assessment of cIMT. Genomic DNA of a subgroup of RA patients was extracted from EDTA blood leukocytes to analyse b2-adrenoceptor polymorphism (β₂AR-SNPs) at codon positions 16, 27 and 164 [3].

Results: RA patients had a higher prevalence of plaques compare to the controls (34.6% vs. 21.6%). Moderate and high-grade stenosis was observed in 9% RA patients versus 3% OA patients. The mean cIMT was also higher in RA patients (0.992 ± 0.391 mm). Genetic analysis of a subgroup of RA patients revealed a moderate correlation between the Arg16 polymorphism of β₂AR and cIMT (Z = –1.956, p = 0.05). In multivariate regression analysis, age (β = 0.374, p = 0.001) and disease activity (DAS28 > 2,6; β = 0.311, p = 0.007) were identified as independent predictors of increased cIMT in RA patients, while BMI, low-density lipoprotein, CRP, RF/Anti-CCP, and radiological erosions showed no significant correlations.

Conclusion: Both traditional atherosclerosis risk factors and RA disease activity may contribute to the development of atherosclerosis in RA patients. Additionally, the Arg16 polymorphism of the β₂AR was positively associated with cIMT functioning as surrogate of atherosclerotic changes in this patient group. Further studies are warranted to determine the role of genetic factors on arteriosclerosis.

Disclosures: AM declares no conflicts of interest.

References

[1] Weber BN, Giles JT, Liao KP. Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease. Nat Rev Rheumatol. 2023 Jul;19(7):417-428. DOI: 10.1038/s41584-023-00969-7
[2] Libby P. The changing landscape of atherosclerosis. Nature. 2021 Apr;592(7855):524-533. DOI: 10.1038/s41586-021-03392-8
[3] Metaxa S, Missouris C, Mavrogianni D, Miliou A, Oikonomou E, Toli E, Kormali L, Vlismas A, Drakakis P, Tousoulis D. Polymorphism Gln27Glu of β2 Adrenergic Receptors in Patients with Ischaemic Cardiomyopathy. Curr Vasc Pharmacol. 2018;16(6):618-623. DOI: 10.2174/1570161115666170919180959
[4] Malysheva O, Pierer M, Wagner U, Wahle M, Wagner U, Baerwald CG. Association between beta2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope. Ann Rheum Dis. 2008 Dec;67(12):1759-64. DOI: 10.1136/ard.2007.083782