Early predictor of high cardiovascular risk in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease associated with a high risk of cardiovascular disease (CVD). Modern studies show that patients with SLE are susceptible to early development of atherosclerosis, which increases the risk of heart attacks and strokes even in young patients. An early predictor of cardiovascular disease (CVD) is arterial stiffness (AS), the assessment of which using such parameters as pulse wave velocity (PWV) and augmentation index (AIx) makes it possible to detect reduced elasticity of the vascular walls. However, the mechanisms of its development in these patients have not been fully studied, and the diagnostic and prognostic values require further study. Thus, the study of arterial stiffness in patients with SLE is of significant scientific and clinical interest.

The aim – to study the parameters of local arterial stiffness in patients with systemic lupus erythematosus and their relationship with traditional risk factors, the QRISK-3 cardiovascular risk score and clinical and immunological indicators Materials and methods. The study included 114 patients with SLE and 35 ageand sex-matched control participants. Women predominated in the SLE group (88%), with a mean age of 37±11 years. The most common clinical manifestations of SLE at the time of enrollment were joint involvement – in 67 (59%) patients, skin involvement – in 36 (31%), and hematologic disorders – in 34 (30%). A positive ANA was detected in 100% of cases, elevated anti-dsDNA levels in 80 (70%) patients, and hypocomplementemia in 76 (67%). Glucocorticoid therapy was received by 91 (80%) patients, hydroxychloroquine – by 80 (70%) and other cytostatic drugs – by 39 (34%) at the time of inclusion in the study. All participants underwent ultrasound of the common carotid arteries with a study of the AIx and pulse wave velocity (PWV) in the supine position. Before the ultrasound, all patients underwent physical, instrumental and laboratory examinations, the presence of traditional risk factors (TRF) was assessed, and the risk of developing CVD was calculated using the QRISK-3 scale.

Results. In patients with SLE, higher AS values were found compared to the control group: AIx on the left – 1.9 [–0.2; 5.3] vs 0.0 [–1.1; 2.1]%; AIx on the right – 1.1 [–0.1; 5.1] vs 0.1 [–0.6; 2.3]%; PWV on the left – 7.2 [6.1; 8.4] vs 6.6 [5.8; 7.6] m/s, respectively (p<0.05 in all cases). A relationship was found between AR and TRF – age, arterial hypertension and dyslipidemia, QRISK-3. In patients with SLE who have atherosclerotic plaques (AP), vascular stiffness is higher compared to patients without AP. A correlation was found between PWV and AIx with immunological parameters (antiβ2-GP1, anti Ro/SS-A), intima-media thickness, and QRISK-3.

Conclusions. The obtained results emphasize the multifactorial mechanism of vascular changes in SLE, including TGF, SLE-related factors. These data can serve as a basis for more accurate risk stratification and personalized selection of therapy in patients with SLE.

1. Nasonov EL, Soloviev SK, Arshinov AV. Systemic lupus erythematosus: History and modernity. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2022;60(4):397-412 (In Russ.). doi: 10.47360/1995-4484-2022-397-41

2. Conrad N, Verbeke G, Molenberghs G, Goetschalckx L, Callender T, Cambridge G, et al. Autoimmune diseases and cardiovascular risk: A population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. Lancet. 2022; 400(10354):733-743. doi: 10.1016/S0140-6736(22)01349-6

3. Dai X, Fan Y, Zhao X. Systemic lupus erythematosus: Updated insights on the pathogenesis, diagnosis, prevention and therapeutics. Signal Transduct Target Ther. 2025;10(1):102. doi: 10.1038/s41392-025-02168-0

4. McMahon M, Seto R, Skaggs BJ. Cardiovascular disease in systemic lupus erythematosus. Rheumatol Immunol Res. 2021;2(3):157-172. doi: 10.2478/rir-2021-0022

5. Vasyuk YuA, Ivanova SV, Shkolnik EL, Kotovskaya YuV, Milyagin VA, Oleynikov VE, et al. Consensus of Russian experts on the evaluation of arterial stiffness in clinical practice. Cardiovascular Therapy and Prevention. 2016;15(2):4-19 (In Russ.). doi: 10.15829/1728-8800-2016-2-4-19

6. Triantafyllias K, Thiele LE, Cavagna L, Baraliakos X, Bertsias G, Schwarting A. Arterial stiffness as a surrogate marker of cardiovascular disease and atherosclerosis in patients with arthritides and connective tissue diseases: A literature review. Diagnostics (Basel). 2023;13(11):1870. doi: 10.3390/diagnostics13111870

7. Berger M, Fesler P, Roubille C. Arterial stiffness, the hidden face of cardiovascular risk in autoimmune and chronic inflammatory rheumatic diseases. Autoimmun Rev. 2021;20(9):102891. doi: 10.1016/j.autrev.2021.102891

8. Townsend RR, Wilkinson IB, Schiffrin EL, Avolio AP, Chirinos JA, Cockcroft JR, et al.; American Heart Association Council on Hypertension. Recommendations for improving and standardizing vascular research on arterial stiffness: A scientific statement from the American Heart Association. Hypertension. 2015;66(3):698-722. doi: 10.1161/HYP.0000000000000033

9. Arida A, Protogerou AD, Kitas GD, Sfikakis PP. Systemic inflammatory response and atherosclerosis: The paradigm of chronic inflammatory rheumatic diseases. Int J Mol Sci. 2018;19(7):1890. doi: 10.3390/ijms19071890

10. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686. doi: 10.1002/art.34473

11. Aseeva EA, Solovyev SK, Nasonov EL. Current methods for evaluating the activity of systemic lupus erythematosus. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2013;51(2): 186-200 (In Russ.). doi: 10.14412/1995-4484-2013-648

12. Solovyeva ES, Aseeva EA, Lisitsyna TA, Popkova TV, Solovyev SK, Nasonov EL. Irreversible organ damages in patients with systemic lupus erythematosus. SLICC damage index. Modern Rheumatology Journal. 2016;10(1):56-62 (In Russ.). doi: 10.14412/1996-7012-2016-1-56-62

13. Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: Prospective cohort study. BMJ. 2017;357:j2099. doi: 10.1136/bmj.j2099

14. Ezhov MV, Kukharchuk VV, Sergienko IV, Alieva AS, Antsiferov MB, Ansheles AA, et al. Disorders of lipid metabolism. Clinical guidelines 2023. Russian Journal of Cardiology. 2023;28(5):5471 (In Russ.). doi: 10.15829/15604071-2023-5471

15. Stortz M, Triantafyllias K, Schwarting A, Weinmann-Menke J. Vascular stiffness: Influencing factors on carotid-femoral pulse wave velocity in systemic lupus erythematosus. Clin Exp Rheumatol. 2020;38(1):74-81.

16. Söderström M, Grönlund C, Liv P, Nyman E, Näslund U, Wester P. Aortic arterial stiffness associates with carotid intima-media thickness and carotid plaques in younger middle-aged healthy people. Blood Press. 2024;33(1):2405161. doi: 10.1080/08037051.2024.2405161

17. Čypienė A, Dadonienė J, Miltinienė D, Rinkūnien E, Rugienė R, Stropuvienė S, et al. The fact not to ignore: Mean blood pressure is the main predictor of increased arterial stiffness in patients with systemic rheumatic diseases. Adv Med Sci. 2017;62(2):223-229. doi: 10.1016/j.advms.2017.01.005

18. Valero-Gonzalez S, Castejon R, Jimenez-Ortiz C, Rosado S, Tutor-Ureta P, Vargas JA, et al. Increased arterial stiffness is independently associated with metabolic syndrome and damage index in systemic lupus erythematosus patients. Scand J Rheumatol. 2014;43(1):54-58. doi: 10.3109/03009742.2013.803150

19. McDonnell T, Wincup C, Buchholz I, Pericleous C, Giles I, Ripoll V, et al. The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS. Blood Rev. 2020;39:100610. doi: 10.1016/j.blre.2019.100610

20. Parra S, Lopez-Dupla M, Ibarretxe D, de Las Heras M, Amigó N, Català A, et al. Patients with systemic lupus erythematosus show an increased arterial stiffness that is predicted by IgM anti-β2glycoprotein I and small dense high-density lipoprotein particles. Arthritis Care Res (Hoboken). 2019;71(1):116-125. doi: 10.1002/acr.23594

21. Mangoni AA, Sotgia S, Zinellu A, Carru C, Pintus G, Damiani G, et al. Methotrexate and cardiovascular prevention: An appraisal of the current evidence. Ther Adv Cardiovasc Dis. 2023;17:17539447231215213. doi: 10.1177/17539447231215213

22. Verhoeven F, Prati C, Chouk M, Demougeot C, Wendling D. Methotrexate and cardiovascular risk in rheumatic diseases: A comprehensive review. Expert Rev Clin Pharmacol. 2021;14(9):1105-1112. doi: 10.1080/17512433.2021.1932461

23. Xie F, Chen L, Yun H, Levitan EB, Curtis JR. Benefits of methotrexate use on cardiovascular disease risk among rheumatoid arthritis patients initiating biologic disease-modifying antirheumatic drugs. J Rheumatol. 2021;48(6):804-812. doi: 10.3899/jrheum.191326