PROGNOSTIC SIGNIFICANCE OF LIPID METABOLISM PARAMETERS AND SYSTEMIC INFLAMMATION FOR THE DEVELOPMENT OF CAROTID ARTERY ATHEROSCLEROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Highlights

• In patients with rheumatoid arthritis, lipid profile indicators do not allow one to fully assess the severity of atherosclerosis. The systemic inflammatory response index, the systemic immune inflammation index, and the neutrophil-lymphocyte ratio are prognostically significant in assessing the likelihood of atherosclerotic plaque development in the carotid arteries in patients with rheumatoid arthritis.

Aim. To study the role of lipid metabolism disorders and systemic inflammation in the pathogenesis of carotid artery (CA) atherosclerosis in patients with rheumatoid arthritis (RA).

Methods. Thirty patients with RA underwent ultrasound duplex scanning of the CA (USDS CA). The criterion for the presence of an atherosclerotic plaque (AP) was local thickening of the CA by more than 50% compared to the surrounding areas. A complete blood count was assessed, including the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) values, and lipidogram parameters. Based on the general blood test data, indices reflecting the activity of systemic inflammation were calculated.

Results. According to the results of USDS CA the patients were divided into 2 groups: group 1 - with the presence of AP in the CA (n = 19) and group 2 without AP in the CA (n = 11). Patients with the presence of AP in the CA had lower triglyceride values ​​than those without AP (1,27 ± 0,48 vs. 1,73 ± 0,5 mmol/L, p = 0,02). The levels ​​of total serum cholesterol, low-density lipoproteins and high-density lipoproteins were not statistically distinguishable between the two groups. The Castelli risk indices 1 and 2, the atherogenic index of plasma as well as the atherogenicity coefficient and the combined lipoprotein index showed no significant differences between the study groups. The systemic inflammatory response index (SIRI), neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), ESR and CRP values ​​were higher in patients with AP in CA. Smoking, a family history of cardiovascular diseases, concomitant hypertension, and systemic glucocorticosteroid treatment were not linked to the development of CA.

Conclusion. Lipid metabolism paremeters, as well as indices based on lipidogram data, were not associated with the risk of developing CA atherosclerosis in patients with RA. NLR, SII, SIRI, as well as ESR and CRP are prognostically significant in determining the risk of developing atherosclerotic CA lesions.

1. D'Orazio A, Cirillo AL, Greco G, Di Ruscio E, Latorre M, Pisani F, Alunno A, Puxeddu I. Pathogenesis of rheumatoid arthritis: one year in review 2024 // Clin Exp Rheumatol. 2024; 42 (9):1707-1713. doi: 10.55563/clinexprheumatol/0307ed.

2. GBD 2021 Rheumatoid Arthritis Collaborators. Global, regional,

3. and national burden of rheumatoid arthritis, 1990–2020, and pro-

4. jections to 2050: A systematic analysis of the Global Burden

5. of Disease Study 2021. Lancet Rheumatol. 2023; 5 (10):e594-e610.

6. doi: 10.1016/S2665-9913(23)00211-4

7. Global Health Metrics. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2018; 392 (10159):1736–1788. doi: 10.1016/S0140-6736(18)32203-7

8. Popescu D, Rezus E, Badescu MC, Dima N, Seritean Isac PN, Dragoi IT, Rezus C. Cardiovascular Risk Assessment in Rheumatoid Arthritis: Accelerated Atherosclerosis, New Biomarkers, and the Effects of Biological Therapy. Life. 2023; 13:319. doi: 10.3390/life13020319.

9. Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012;71(9):1524-9. doi: 10.1136/annrheumdis-2011-200726.

10. Pope JE, Nevskaya T, Barra L, Parraga G. Carotid Artery Atherosclerosis in Patients with Active Rheumatoid Arthritis: Predictors of Plaque Occurrence and Progression Over 24 Weeks. Open Rheumatol J. 2016; 10:49-59. doi:10.2174/1874312901610010049

11. Fomicheva OA, Popkova TV, Krougly LB, Gerasimova EV, Novikova DS, Pogorelova OA. et al. Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis. Kardiologiia. 2021; 61 (1):12–21. doi: 10.18087/cardio.2021.1.n1331 (In Russian)

12. Gimbrone MA Jr, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301

13. Tsiantoulas D, Sage AP, Mallat Z, Binder CJ. Targeting B cells in atherosclerosis: closing the gap from bench to bedside. Arterioscler Thromb Vasc Biol. 2015;35:296–302. doi: 10.1161/ATVBAHA.114.303569

14. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, et al. et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010; 62(9):2569–8c1. doi:10.1002/art.27584

15. Rheumatoid arthritis. Clinical guidelines 2024. Available at: https://cr.minzdrav.gov.ru/preview-cr/250_3 (accessed 19.03.25)

16. Ezhov MV, Kukharchuk VV, Sergienko IV, et al. Disorders of lipid metabolism. Clinical Guidelines 2023. Russian Journal of Cardiology. 2023;28(5):5471. doi:10.15829/1560-4071-2023-5471. EDN YVZOWJ

17. Hannawi SM, Hannawi H, Alokaily F, Al Salmi I. Subclinical atherosclerosis in rheumatoid arthritis patients of the Gulf Cooperated Council. Saudi Med J. 2020;41(9):1022-1025. doi: 10.15537/smj.2020.9.25319.

18. Gerasimova EV, Popkova TV, Shalygina MV, Kirillova IG, Gerasimova DA, Glukhova SI, Nasonov EL. Subclinical atherosclerosis of the carotid arteries in patients with rheumatoid arthritis with low cardiovascular risk. Terapevticheskii Arkhiv (Ter. Arkh.). 2023; 95(5):375–379. doi: 10.26442/00403660.2023.05.202203 (In Russian)

19. Pereira-da-Silva T, Napoleão P, Pinheiro T, Selas M, Silva F, Ferreira RC, Carmo MM. The Proinflammatory Soluble CD40 Ligand Is Associated with the Systemic Extent of Stable Atherosclerosis. Medicina (Kaunas). 2021; 57 (1):39. doi: 10.3390/medicina57010039.

20. Koren Krajnc M, Hojs R, Holc I, Knez Ž, Pahor A. Accelerated atherosclerosis in premenopausal women with rheumatoid arthritis - 15-year follow-up. Bosn J Basic Med Sci. 2021; 21 (4):477-483. doi: 10.17305/bjbms.2020.5176.

21. Klimov AN, Nikul'cheva NG. Obmen lipidov i lipoproteidov i ego narushenija. Saint Petersburg: Piter Kom, 1999. 512 p. (In Russian)

22. Starodubova YuN, Osipova IV. Characteristics of dyslipidemia and the duration of rheumatoid arthritis in women. Ateroscleroz. 2017; 13 (3):33-42 (In Russian)

23. Zhao Z, Wang H, Hou Q, Zhou Y, Zhang Y. Non-traditional lipid parameters as potential predictors of carotid plaque vulnerability and stenosis in patients with acute ischemic stroke. Neurol Sci. 2023; 44 (3):835-843. doi: 10.1007/s10072-022-06472-3.

24. Albrektsen G, Heuch I, Løchen ML, Thelle DS, Wilsgaard T, Njølstad I, Bønaa KH. Risk of incident myocardial infarction by gender: Interactions with serum lipids, blood pressure and smoking. The Tromsø Study 1979–2012. Atherosclerosis. 2017; 261:52–59. doi: 10.1016/j.atherosclerosis.2017.04.009.

25. Kouvari M, Panagiotakos DB, Chrysohoou C, Georgousopoulou EN, Tousoulis D, Pitsavos C. Sex-Related Differences of the Effect of Lipoproteins and Apolipoproteins on 10-Year Cardiovascular Disease Risk; Insights from the ATTICA Study (2002–2012) Molecules. 2020; 25:1506. doi: 10.3390/molecules25071506.

26. García-Chagollán M, Hernández-Martínez SE, Rojas-Romero AE, Muñoz-Valle JF, Sigala-Arellano R, Cerpa-Cruz S, Morales-Núñez JJ, Lomelí-Nieto JA, Macedo Ojeda G, Hernández-Bello J. Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical components. J Clin Lab Anal. 2021; 35 (3):e23666.

27. doi: 10.1002/jcla.23666.

28. Vázquez-Del Mercado M, Nuñez-Atahualpa L, Figueroa-Sánchez M, Gómez-Bañuelos E, Rocha-Muñoz AD, Martín-Márquez BT, Corona-Sanchez EG, Martínez-García EA, Macias-Reyes H, Gonzalez-Lopez L, et al. Serum levels of anticyclic citrullinated peptide antibodies, interleukin-6, tumor necrosis factor-α, and C-reactive protein are associated with increased carotid intima-media thickness: A cross-sectional analysis of a cohort of rheumatoid arthritis patients without cardiovascular risk factors. Biomed. Res. Int. 2015; 2015:342649. doi: 10.1155/2015/342649.

29. Hammam N, Abdel-Wahab N, Gheita TA. Atherogenic Index of Plasma in Women with Rheumatoid Arthritis and Systemic Lupus Erythematosus: A 10-Year Potential Predictor of Cardiovascular Disease. Curr Rheumatol Rev. 2021; 17 (1):122-130.

30. doi: 10.2174/1573397116666201007123403.

31. Parveen S, Jacob R, Rajasekhar L, Srinivasa C, Mohan IK. Serum Lipid Alterations in Early Rheumatoid Arthritis Patients on Disease Modifying Anti Rheumatoid Therapy. Indian J Clin Biochem. 2017; 32 (1):26-32. doi: 10.1007/s12291-016-0566-9.

32. Çelik E, Çora AR, Karadem KB. The Effect of Untraditional Lipid Parameters in the Development of Coronary Artery Disease: Atherogenic Index of Plasma, Atherogenic Coefficient and Lipoprotein Combined Index. J Saudi Heart Assoc. 2021; 33 (3):244-250. doi: 10.37616/2212-5043.1266.

33. González-Sierra M, Quevedo-Rodríguez A, Romo-Cordero A, González-Chretien G, Quevedo-Abeledo JC, de Vera-González A, González-Delgado A, Martín-González C, González-Gay MÁ, Ferraz-Amaro I. Relationship of Blood Inflammatory Composite Markers with Cardiovascular Risk Factors and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis. Life (Basel). 2023; 13 (7):1469. doi: 10.3390/life13071469.

34. Shvarts VA, Talibova SM, Sokolskaya MA, Ispiryan AYu, Shvarts EN, Petrosyan AD, Merzlyakov VYu, Skopin AI, Donakanyan SA. Association of novel biomarkers of systemic inflammation with atherosclerosis and its severity. Russian Journal of Cardiology. 2024; 29 (8):6025. doi: 10.15829/1560-4071-2024-6025 (In Russian)

35.