TIME COURSE OF CHANGES IN BLOOD LIPID PARAMETERS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING TREAT-TO-TARGET ANTIRHEUMATIC THERAPY: ACCORDING TO 18-MONTH FOLLOW-UP FINDINGS

The mechanisms for lowering a cardiovascular risk (CVR) in patients with early rheumatoid arthritis (RA) when implementing the treat-to-target strategy remain inadequately investigated.

Objective: to estimate the time course of changes in blood lipid parameters in patients with early RA during Treat-totarget antirheumatic therapy at an 18-month follow-up.

Subjects and methods. Seventy-four patients (73% women; median age, 56 years) with early RA meeting the respective 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and moderate or high activity (median DAS28-ESR score of 5.4) were examined within the framework of the REMARCA trial. After 6-month treatment, RA activity significantly reduced (p < 0.05). At months 6 to 18, no significant change in RA activity was recorded. After 18 months, remission was observed in 31 (42%) patients: in 17 (55%) on methotrexate (MTX) monotherapy and in 14 (45%) on combined therapy with MTX and a biological agent. Blood lipid levels were determined at inclusion in the investigation, 6 and 18 months later. The values of lipid parameters were estimated in terms of the total CVR. 67.6% of the patients were classified as at very high CVR. At 18 months of treatment, 34 (46%) patients were treated with statins (median atorvastatin and rosuvastatin doses were 10 mg/day each).

Results and discussion. Only 12% of the patients had optimal baseline values of just all lipid parameters. The concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) correlated negatively with C-reactive protein (CRP) levels, DAS28-ESR, DAS28-CRP, and HAQ (p < 0.05). After 6-month treatment, there were increases in TC by 7%, LDL-C by 12.5%, and HDL-C by 19.7%, and a decrease in the atherogenic index by 16% (p < 0.05). ΔCRP negatively correlated with ΔTC, ΔLDL-C, and ΔHDL-C (r = -0.3; p < 0.05). A correlation of TC and LDL-C with inflammation markers broke off in the presence of lower RA activity; the investigators began recording a relationship of these lipid parameters to traditional CVR factors. Between 6th and 18th month of treatment, there was no significant change in lipid parameters. Statin therapy resulted in no considerable change in lipid concentrations.

Conclusion. The level of lipids negatively correlates with disease activity in the patients with early RA. During antirheumatic treatment, the lipid concentrations are more elevated with a more intensive decrease in CRP levels. With lowered RA activity, the level of lipids correlates with traditional CVR factors more strongly than with inflammation markers.

1. Насонов ЕЛ, Каратеев ДЕ, Балабанова РМ. Ревматоидный артрит. В кн.: Насонов ЕЛ, Насонова ВА, редакторы. Ревматология. Национальное руководство. Москва: ГЭОТАР-Медиа; 2008. С. 290-331 [Nasonov EL, Karateev DE, Balabanova RM. Rheumatoid arthritis. In: Nasonov EL, Nasonova VA, editors. Revmatologiya. Natsional’noe rukovodstvo [Rheumatology. National guidelines]. Moscow: GEOTAR-Media; 2008. P. 290-331].

2. Solomon DH, Goodson NJ, Katz JN, et al. Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis. 2006;65(12):1608-12. doi: 10.1136/ard.2005.050377

3. Gonzalez-Gay MA, Gonzalez-Juanatey C, Pineiro A, et al. Highgrade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatol. 2005;32:1219-23.

4. Myasoedova E, Crowson CS, Kremers HM, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011;70(3):482-7. doi: 10.1136/ard.2010.135871

5. Lu L, Choi HK, Schoenfeld SR, et al. Improved survival in rheumatoid arthritis: a general population-based study. Ann Rheum Dis. 2015;74:137-8. doi: 10.1136/annrheumdis-2015-eular.3507

6. Kerola AM, Nieminen TV, Virta LJ, et al. No increased cardiovascular mortality among early rheumatoid arthritis patients: a nationwide register study in 2000–2008. Clin Exp Rheumatol. 2015 May-Jun;33(3):391-8. Epub 2015 May 1.

7. Van den Hoek J, Roorda LD, Boshuizen HC, et al. Trend in and predictors for cardiovascular mortality in patients with rheumatoid arthritis over a period of 15 years: a prospective cohort study. Ann Rheum Dis. 2015;74 Suppl 2:692. doi: 10.1136/annrheumdis-2015- eular.1730

8. Holmqvist M, Ljung L, Askling J. Acute coronary syndrome in rheumatoid arthritis: are patients diagnosed today also at increased risk? Ann Rheum Dis. 2015;74 Suppl 2:130. doi: 10.1136/annrheumdis-2015-eular. 6244

9. Humphreys JH, Warner A, Chipping J, et al. Mortality trends in patients with early rheumatoid arthritis over 20 years: Results from the Norfolk Arthritis Register. Arthritis Care Res (Hoboken). 2014 Feb 4. doi: 10.1002/acr.22296

10. Gonzalez-Gay MA, Gonzalez-Juanatey C. Inflammation and lipid profile in rheumatoid arthritis: bridging an apparent paradox. Ann Rheum Dis. 2014 Jul;73(7):1281-3. doi: 10.1136/annrheumdis-2013-204933

11. Navarro-Millan I, Charles-Schoeman C, Yang S, et al. Changes in lipoproteins associated with treatment with methotrexate or combination therapy in early rheumatoid arthritis: results from the TEAR trial. Arthritis Rheum. 2013;65(6):1430-8. doi: 10.1002/art.37916

12. Boers M, Nurmohamed MT, Doelman CJ, et al. Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62(9):842-5. doi: 10.1136/ard.62.9.842

13. Каратеев ДЕ, Лучихина ЕЛ, Муравьев ЮВ и др. Российское стратегическое исследование фармакотерапии ревматоидного артрита (РЕМАРКА). Научно-практическая ревматология. 2013;51(2):117-25 [Karateev DE, Luchikhina EL, Muravyev YV, et al. The first Russian strategic study of pharmacotherapy for rheumatoid arthritis (REMARCA). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(2):117-25 (In Russ.)]. doi: 10.14412/1995-4484-2013-637

14. Новикова ДС, Попкова ТВ, Кириллова ИГ и др. Оценка кардиоваскулярного риска у больных ранним ревматоидным артритом в рамках исследования РЕМАРКА (предварительные данные). Научно-практическая ревматология. 2015;53(1):24-31 [Novikova DS, Popkova TV, Kirillova IG, et al. Cardiovascular risk assessment in patients with early rheumatoid arthritis within the REMARCA study: Preliminary data. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(1):24-31 (In Russ.)]. doi: 10.14412/1995-4484-2015-24-31

15. Российское кардиологическое общество. Национальное общество по изучению атеросклероза. Российское общество кардиосоматической реабилитации и вторичной профилактики. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации (V пересмотр). Раздел 3. Обследование пациентов и оценка риска развития сердечно-сосудистых осложнений. Москва; 2012 [Rossiiskoe kardiologicheskoe obshchestvo. Natsional'noe obshchestvo po izucheniyu ateroskleroza. Rossiiskoe obshchestvo kardiosomaticheskoi reabilitatsii i vtorichnoi profilaktiki. Diagnostika i korrektsiya narushenii lipidnogo obmena s tsel'yu profilaktiki i lecheniya ateroskleroza. Rossiiskie rekomendatsii (V peresmotr). Razdel 3. Obsledovanie patsientov i otsenka riska razvitiya serdechno-sosudis￾tykh oslozhnenii [Russian Society of Cardiology. National Society for the Study of Atherosclerosis. Russian Society Cardiosomatic Rehabilitation and Secondary Prevention. Diagnostics and correc￾tion of disorders of lipid metabolism in the prevention and treatment of atherosclerosis. Russian recommendations (V revision). Section 3. The examination of patients and evaluation of the risk of cardiovascular complications]. Moscow; 2012].

16. Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. JACC. 1990;15:827-32. doi: 10.1016/0735-1097(90)90282-T

17. Национальные рекомендации по кардиоваскулярной профилактике. Комитет экспертов РКО. Кардиоваскулярная терапия и профилактика. 2011;10(6) Прил. 2:46 [National guidelines on cardiovascular prevention. The Committee of Experts RCS. Kardiovaskulyarnaya Terapiya i Profilaktika. 2011;10(6) Suppl 2:46 (In Russ.)].

18. Boyer JF, Gourraud PA, Cantagrel A, et al. Traditional cardiovascular risk factors in rheumatoid arthritis: a meta-analysis. Joint Bone Spine. 2011 Mar;78(2):179-83. doi: 10.1016/j.jbspin.2010.07.016 19. Chung CP, Giles JT, Petri M, et al. Prevalence of traditional modifiable cardiovascular risk factors in patients with rheumatoid arthritis: comparison with control subjects from the multi-ethnic study of atherosclerosis. Semin Arthritis Rheum. 2012;41(4):535-44. doi: 10.1016/j.semarthrit.2011.07.004

19. Бойцов СА, Кухарчук ВВ, Карпов ЮА и др. Субклинический атеросклероз как фактор риска сердечно-сосудистых осложнений. Кардиоваскулярная терапия и профилактика. 2012;11(3):82-6 [Boitsov SA, Kukharchuk VV, Karpov YuA, et al. Subclinical atherosclerosis as a risk factor for cardiovascular complications. Kardiovaskulyarnaya Terapiya i Profilaktika. 2012;11(3):82-6 (In Russ.)].

20. Воробьева ЕН, Казызаева АС, Шарлаева ЕА и др. Частота дислипидемий у жителей городской популяции. Известия Алтайского государственного университета. 2014;83(3/2);30-4 [Vorob’eva EN, Kazyzaeva AS, Sharlaeva EA, et al. The frequency of dyslipidemia among residents of urban population. Izvestiya Altaiskogo Gosudarstvennogo Universiteta. 2014;83(3/2);30-4 (In Russ.)].

21. Никитин ЮП, Макаренкова КВ, Малютина СК и др. Липидные параметры крови в российской, польской и чешской популяциях: The Hapiee Study. Кардиология. 2015;(5):34-9 [Nikitin YuP, Makarenkova KV, Malyutina SK, et al. Blood lipid parameters in the Russian, Polish and Czech populations: The Hapiee Study. Kardiologiya. 2015;(5):34-9 (In Russ.)].

22. Rizzo M, Spinas GA, Cesur M, et al. Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naive patients with early rheumatoid arthritis. Atherosclerosis. 2009;207(2):502-6. doi: 10.1016/j.atherosclerosis.2009.07.015

23. Chung CP, Oeser A, Raggi P, et al. Lipoprotein subclasses deter￾mined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis. J Rheumatol. 2010;37(8):1633-8. doi: 10.3899/jrheum.090639

24. Горбунова ЮН, Новикова ДС, Попкова ТВ и др. Кардиоваскулярный риск у больных ранним ревматоидным артритом до назначения базисной противовоспалительной терапии (предварительные данные исследования РЕМАРКА). Научно-практическая ревматология. 2014;52(4):381-6 [Gorbunova YuN, Novikova DS, Popkova TV, et al. Cardiovascular risk in patients with early rheumatoid arthritis before disease-modifying antirheumatic therapy (preliminary data of the REMARCА study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(4):381-6 (In Russ.)]. doi:10.14412/1995-4484-2014-381-386

25. Cavagna L, Boffini N, Cagnotto G, et al. Atherosclerosis and rheumatoid arthritis: more than a simple association. Mediators Inflamm. 2012;2012:147354. doi: 10.1155/2012/147354