rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2011-63rsp-347Research ArticleСтатьиArticlesИНТЕРЛЕЙКИН 6 И СЕРДЕЧНО-СОСУДИСТАЯ ПАТОЛОГИЯ ПРИ РЕВМАТОИДНОМ АРТРИТЕINTERLEYKIN 6 I SERDEChNO-SOSUDISTAYa PATOLOGIYa PRI REVMATOIDNOM ARTRITEПопковаТ. В.PopkovaTatyana Valentinovnapopkovatv@mail.ru <mailto:popkovatv@mail.ru>NovikovD SNovikovD S-НасоновЕвгений ЛьвовичNasonovE L-201115082011494№4 (2011)6472Copyright © Попкова Т.В., Novikov D.S., Насонов Е.Л., 20112011Попкова Т.В., Novikov D.S., Насонов Е.Л.Popkova T.V., Novikov D.S., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/347References<div><p>Попкова Т.В., Новикова Д.С., Насонов Е.Л. Атеросклероз при ревматических заболеваниях. В кн.: Ревматология: клинические рекомендации. M.: ГЭОТАР-Медиа, 2010;678-702.</p><p>Peters M.J., Symmons D.P., McCarey D.W. et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis - TASK FORCE «Cardiovascular risk management in RA». Ann Rheum Dis 2010; 69(2):325-31.</p><p>Meune C., Touze E., Trinqurte L. et al. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analisis of cohort studies. Rheumatology 2009; 48(10):1309-13.</p><p>Van Halm V.P., Peters M.J., Voskuyl A.E. et al. Rheumatoid arthritis versus type 2 diabetes as a risk factor for cardiovascular disease: a cross-sectional study. Ann Rheum Dis 2009;68:1395-400.</p><p>Sattar N., McCarey D.W., Capell H. et al. Eхрlaining how «high-grade» systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 2003; 108:2957-63.</p><p>Александрова Е.Н., Новиков А.А., Насонов Е.Л. Высокочувствительные методы определения С-реактивного белка (обзор литературы). Клин лаб диагност 2004;11:16-8.</p><p>Karlson E.W., Chibnik L.B., Tworoger S.S. et al. Biomarkers of inflammation and development of rheumatoid arthritis in women from two prospective cohort studies. Arthr Rheum 2009;60(3):641-52.</p><p>Goodson N.I., Willes N.J., Lunt N.C. Mortality on early inflammatory arthritis: cardiovascular mortality in seropositive patients. Arthr Rheum 2002;46:2010-9.</p><p>Gerli R., Bartoloni Bocci E., Sherer Y. et al. Association of anti-cyclic citrullinated peptide antibodies with subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum Dis 2008;67:724-5.</p><p>Marardit-Kremers H., Nicola P.J., Crowson C.S. et al. Cardiovascular death in rheumatoid arthritis. A population-based study. Arthr Rheum 2005;52:722-32.</p><p>Насонов Е.Л. Антифосфолипидный синдром. М.: Литтерра, 2004.</p><p>Tedgui A., Mallat Z. Anti-inflammatory mechanisms in the vascular wall. Circ Res 2001;88(9):877-87.</p><p>Brennan F.M., McInnes I.B. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 2008; 118(11):3537-45.</p><p>Dayer J.M., Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford) 2010; 49(1):15-24.</p><p>Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340(6):448-54.</p><p>Woods A., Brull D.J., Humphries S.E., Montgomery H.E. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur Heart J 2000; 21(19):1574-83.</p><p>Rattazzi M., Puato M., Faggin E. et al. C-reactive protein and interleukin-6 in vascular disease: culprits or passive bystanders? J Hypertens 2003;21(10):1787-803.</p><p>Pepys M.B., Hirschfield G.M. C-reactive protein: a critical update. J Clin Invest 2003; 111(12):1805-12.</p><p>Насонов Е.Л., Панюгова Е.В., Александрова Е.Н. С-реактивный белок - маркер воспаления при атеросклерозе (новые данные). Кардиология 2002; 7:53-62.</p><p>Naka T., Nishimoto N., Kishimoto T. The paradigm of IL-6: from basic science to medicine. Arthr Res 2002;4(Suppl. 3): 233-42.</p><p>Heinrich P.C., Behrmann I., Haan S. et al. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003;15(374):1-20.</p><p>Rose-John S., Scheller J., Elson G., Jones S.A. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol 2006;80(2):227-36.</p><p>Насонов Е.Л. Новые возможности фармакотерапии ревматических болезней - ингибирование интерлейкина 6. Клин фармакол тер 2008;17(1):2-8.</p><p>Sack U., Kinne R.W., Marx T. Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. Rheumatol Int 1993;13(2):45-51.</p><p>Madhok R., Crilly A., Watson J. Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis 1993;52(3):232-4.</p><p>Bermudez E.A., Rifai N., Buring J. et al. Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 2002; 22(10):1668-73.</p><p>Fernandez-Real J.M., Vayreda M., Richart C. et al. Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001;86(3):1154-9.</p><p>Brady S.R., de Courten B., Reid C.M. The role of traditional cardiovascular risk factors among patients with rheumatoid arthritis. J Rheumatol 2009;36(1):34-40.</p><p>Dessein P.H., Joffe B.I. Suppression of circulating interleukin-6 concentrations is associated with decreased endothelial activation in rheumatoid arthritis. Clin Exp Rheumatol 2006;24(2):161-7</p><p>Esteve E., Castro A., Lоpez-Bermejo A. et al. Serum interleukin-6 correlates with endothelial dysfunction in healthy men independently of insulin sensitivity. Diabetes Care 2007;30(4):939-45.</p><p>Mahmud A., Feely J. Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension 2005; 46(5):1118-22.</p><p>Salomon R.N., Underwood R., Doyle M.V. et al. Increased apolipoprotein E and c-fms gene expression without elevated interleukin 1 or 6 mRNA levels indicates selective activation of macrophage functions in advanced human atheroma. Proc Natl Acad Sci USA 1992;89(7):2814-8.</p><p>Seino Y., Ikeda U., Ikeda M. Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. Cytokine 1994; 6(1):87-91.</p><p>Koenig W., Khuseyinova N. Biomarkers of atherosclerotic plaque instability and rupture. Arterioscler Thromb Vasc Biol 2007; 1:15-26.</p><p>Danesh J., Kaptoge S., Mann A.G. et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med 2008;5(4):600-10.</p><p>Ridker P.M., Rifai N., Stampfer M.J. et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101(15):1767-72.</p><p>Volpato S., Guralnik J.M., Ferrucci L. et al. Cardiovascular disease, interleukin-6, and risk of mortality in older women: the women's health and aging study. Circulation 2001;103(7):947-53.</p><p>Harris T.B., Ferrucci L., Tracy R.P. et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 1999;106(5):506-12.</p><p>Ridker P.M., Hennekens C.H., Buring J.E. et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;23:342(12):836-43</p><p>Biasucci L.M., Vitelli A., Liuzzo G. et al. Elevated levels of interleukin-6 in unstable angina. Circulation 1996;94(5):874-7.</p><p>Biasucci L.M., Liuzzo G., Fantuzzi G. et al. Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation 1999;99(16):2079-84.</p><p>Cusack M., Odemuyiwa S., Kamalvand K. et al. Can systemic markers of inflammation accurately predict short-term outcome in patients with unstable coronary syndrome? J Amer Coll Cardiol 2001;37(Suppl. A):359A.</p><p>Dinh W., Fü th R., Nickl W. et al. Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders. Cardiovasc Diabetol 2009;12(8):58.</p><p>Whiteley W., Jackson C., Lewis S. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med 2009;6(9):e100014</p><p>Gotsman I., Stabholz A., Planer D. et al. Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden? Isr Med Assoc J 2008;10(7):494-8.</p><p>Schieffer B., Schieffer E., Hilfiker- Kleiner D. et al. Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability. Circulation 2000;101(12):1372-8.</p><p>Funakoshi Y., Ichiki T., Ito K., Takeshita A. Induction of interleukin-6 expression by angiotensin II in rat vascular smooth muscle cells. Hypertension 1999;34(1):118-25.</p><p>Sadoshima J. Cytokine actions of angiotensin II. Circ Res 2000; 86(12):1187-9.</p><p>Suzuki Y., Ruiz-Ortega M., Lorenzo O. Inflammation and angiotensin II. Int J Biochem Cell Biol 2003;35(6):881-900.</p><p>Kuo L.T., Yang N.I., Cherng W.J. Serum interleukin-6 levels, not genotype, correlate with coronary plaque complexity. Int Heart J 2008;49(4):391-402.</p><p>Hoshi T., Kitagawa K., Yamagami H. et al. Relation between interleukin-6 level and subclinical intracranial large-artery atherosclerosis. Atherosclerosis 2008; 197(1):326-32.</p><p>Ingegnoli F., Fantini F., Favalli E.G. et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade. J Autoimmun 2008; 31(2):175-9.</p><p>Oleksowicz L., Mrowiec Z., Zuckerman D. et al. Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism. Thromb Haemost 1994;72(2):302-8.</p><p>Ridker P.M., Cushman M., Stampfer M.J. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336(14):973-9.</p><p>Humphries S.E., Luong L.A., Ogg M.S. et al. The interleukin-6-174G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 2001; 22(24):2243-52.</p><p>Brull D.J., Montgomery H.E., Sanders J. et al. Interleukin-6 gene -174g>c and-572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 2001;21(9):1458-63</p><p>Aker S., Bantis C., Reis P. et al. Influence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients. Nephrol Dial Transplant 2009;24(9):2847-51.</p><p>Gaudino M., Andreotti F., Zamparelli R. et al. The -174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication? Circulation 2003;9;108(Suppl. 1): 195-9.</p><p>Panoulas V.F., Stavropoulos-Kalinoglou A., Metsios G.S. et al. Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking. Atherosclerosis 2009; 204(1):178-83.</p><p>Palomino-Morales R., Gonzalez-Juanatey C., Vazquez-Rodriguez T.R. et al. Interleukin-6 gene -174 promoter polymorphism is associated with endothelial dysfunction but not with disease susceptibility in patients with rheumatoid arthritis. Clin Exp Rheumatol 2009;27(6):964-70.</p><p>Попкова Т.В., Новикова Д.С., Насонов Е.Л. Кардиоваскулярные факторы риска при ревматических заболеваниях: связь с воспалением. Consilium medicum 2010;2:112-8</p><p>Gonzalez-Gay M.A., De Matias J.M., Gonzalez-Juanatey C. et al. Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis. Clin Exp Rheumatol 2006; 24:83-6.</p><p>Fernandez-Real J.M., Vayreda M., Richart C. et al. Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001;86(3):1154-9.</p><p>Bermudez E.A., Rifai N., Buring J. et al. Interrelationships among circulating interleukin-6, C-reactive protein and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 2002; 22:1668-73</p><p>Schillaci G., Pirro M., Gemelli F. et al. Increased C-reactive protein concentrations in never-treated hypertension: the role of systolic and pulse pressures. J Hypertens 2003;21:1841-6.</p><p>Kim K., Lee J.H., Chang H.J. et al. Association between blood pressure variability and inflammatory marker in hypertensive patients. Circ J 2008;72:293-8.</p><p>Panoulas V.F., Douglas K.M., Smith J.P. et al. Galectin-2 (LGALS2) 3279C/T polymorphism may be independently associated with diastolic blood pressure in patients with rheumatoid arthritis. Clin Exp Hypertens 2009;31(2):93-104.</p><p>Vgontzas A.N., Papanicolaou D.A., Bixler E.O. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997;82(5):1313-6.</p><p>Mohamed-Ali V., Goodrick S., Rawesh A. et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997;82(12):4196-200.</p><p>Langenberg C., Bergstrom J., Scheidt-Nave C. et al. Cardiovascular death and the metabolic syndrome: role of adipositysignaling hormones and inflammatory markers. Diabetes Care 2006;29(6):1363-9.</p><p>Libby P., Ridker P.M., Maseri A. Inflammation and atherosclerosis. Circulation 2002;105(9):1135-43.</p><p>Straub R.H., Hense H.W., Andus T. Hormone replacement therapy and interrelation between serum interleukin-6 and body mass index in postmenopausal women: a population-based study. J Clin Endocrinol Metab 2000;85(3):1340-4.</p><p>Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol 2005;78(4):819-35.</p><p>Carey A.L., Febbraio M.A. Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia 2004;47(7):1135-42.</p><p>Rotter V., Nagaev I., Smith U. et al. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overex-pressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003; 278(46):45777-84.</p><p>Kirwan J.P. Insulin sensitivity in skeletal muscle: «use it or lose it, fast». J Appl Physiol 2010;108(5):1023-4.</p><p>Chung C.P., Oeser A., Solus J.F. et al. Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthr Rheum 2008;58(7):2105-12</p><p>Tappia P.S., Troughton K.L., Langley-Evans S.C. et al. Cigarette smoking influences cytokine production and antioxidant defences. Clin Sci (London) 1995; 88(4):485-9.</p><p>Del Ruicon I.D., Williams K., Stern M.P. et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthr Rheum 2001;44(12):2737-45.</p><p>Dessein P.H., Joffe B.I., Veller M.G. et al. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J Rheumatol 2005;32(3):435-42.</p><p>Sattar N., Crompton P., Cherry L. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthr Rheum 2007;56:831-9.</p><p>Попкова Т.В., Новикова Д.С., Новиков А.А. и др. Роль нарушений в системе транспорта холестерина крови в развитии атеросклероза при ревматоидном артрите. Науч-практич ревматол 2007; 5:4-10.</p><p>Nielen M.J., van Halm V.P., Nurmohamed M.T. et al. Rheumatoid arthritis is preceded by a preclinical phase, characterized by increased C-reactive protein levels and a more atherogenic lipid profile. Arthr Rheum 2003;48:344</p><p>Van Halm V.P., Nielen M.J., Nurmohamed M.T. et al. Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Ann Rheum Dis 2006;3:1-5.</p><p>Ettinger W.H., Varma V.K., Sorci-Thomas M. et al. Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb 1994;14(1):8-13.</p><p>Khovidhunkit W., Kim M.S., Memon R.A. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 2004;45:1169-96</p><p>Popa C., Netea M.G., Radstake T.R. et al. Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 2005;64:303-5.</p><p>Peters M.J., Symmons D.P., McCarey D.W. et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis - TASK FORCE «Cardiovascular risk management in RA». Ann Rheum Dis 2010;69(2):325-31.</p><p>Choi E., Sattar N. Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis 2009; 68:460-9.</p><p>Новикова Д.С., Попкова Т.В., Насонов Е.Л. Профилактика сердечно-сосудистых осложнений при ревматоидном артрите. Тер арх 2009;5:88-96.</p><p>Nishimoto N., Yoshizaki K., Miyasaka N. et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthr Rheum 2004; 50:1761-9.</p><p>Sattar N. Effect of tocilizumab treatment on lipid parameters (pooled data: OPTION & TOWARD).</p><p>Maini R.N., Taylor P.C., Szechinski J. et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthr Rheum 2006;54:2817-29.</p><p>Nishimoto N., Hashimoto J., Miyasaka N. et al. Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X-ray reader-blinded randomized controlled trial of tocilizumab. Ann Rheum Dis 2007;66:1162-7.</p><p>Kawashiri S.Y., Kawakami A., Yamasaki S. et al. Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis. Rheumatol Int 2009;Dec 19 [Epub. ahead of print</p><p>Gazi I.F., Boumpas D.T., Mikhailidis D.P. et al. Clustering of cardiovascular risk factors in rheumatoid arthritis: the rationale for using statins. Clin Exp Rheum 2007;25:102-11</p><p>Bisoendial R., Stroes E., Kastelein J., Tak P. Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins. Nat Rev Rheumatol 2010;6:157-64.</p><p>Насонов Е.Л. Перспективы применения статинов в ревматологии. Рус мед журн 2003;11:1273-6.</p><p>Abeles A.M., Pillinger M. Statins as anti-infammatory and immunomodulatory agents. A future in rheumatologic therapy? Arthr Rheum 2006;54:393-407.</p><p>Новикова Д.С., Попкова Т.В., Насонов Е.Л. Снижение кардиоваскулярного риска при ревматоидном артрите: двойная польза статинов. Науч-практич ревматол 2010;6:61-71.</p><p>Lazzerini P.E., Lorenzini S., Selvi E. et al. Simvastatin inhibits cytokine production and nuclear factor-kB activation in interleukin 1ß-stimulated synoviocytes from rheumatoid arthritis patients. Clin Exp Rheum 2007;25:696-700.</p><p>Yokota K., Mioyoshi F., Myazaki K. et al. High concentration simvastatin induces apoptosis in fibroblast-like synoviocytes from patients with rheumatoid arthritis. J Rheumatol 2008;35:193-200.</p></div><br /><div><p>Попкова Т.В., Новикова Д.С., Насонов Е.Л. Атеросклероз при ревматических заболеваниях. В кн.: Ревматология: клинические рекомендации. M.: ГЭОТАР-Медиа, 2010;678-702.</p><p>Peters M.J., Symmons D.P., McCarey D.W. et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis - TASK FORCE «Cardiovascular risk management in RA». Ann Rheum Dis 2010; 69(2):325-31.</p><p>Meune C., Touze E., Trinqurte L. et al. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analisis of cohort studies. Rheumatology 2009; 48(10):1309-13.</p><p>Van Halm V.P., Peters M.J., Voskuyl A.E. et al. Rheumatoid arthritis versus type 2 diabetes as a risk factor for cardiovascular disease: a cross-sectional study. Ann Rheum Dis 2009;68:1395-400.</p><p>Sattar N., McCarey D.W., Capell H. et al. Eхрlaining how «high-grade» systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 2003; 108:2957-63.</p><p>Александрова Е.Н., Новиков А.А., Насонов Е.Л. Высокочувствительные методы определения С-реактивного белка (обзор литературы). Клин лаб диагност 2004;11:16-8.</p><p>Karlson E.W., Chibnik L.B., Tworoger S.S. et al. Biomarkers of inflammation and development of rheumatoid arthritis in women from two prospective cohort studies. Arthr Rheum 2009;60(3):641-52.</p><p>Goodson N.I., Willes N.J., Lunt N.C. Mortality on early inflammatory arthritis: cardiovascular mortality in seropositive patients. Arthr Rheum 2002;46:2010-9.</p><p>Gerli R., Bartoloni Bocci E., Sherer Y. et al. Association of anti-cyclic citrullinated peptide antibodies with subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum Dis 2008;67:724-5.</p><p>Marardit-Kremers H., Nicola P.J., Crowson C.S. et al. Cardiovascular death in rheumatoid arthritis. A population-based study. Arthr Rheum 2005;52:722-32.</p><p>Насонов Е.Л. Антифосфолипидный синдром. М.: Литтерра, 2004.</p><p>Tedgui A., Mallat Z. Anti-inflammatory mechanisms in the vascular wall. Circ Res 2001;88(9):877-87.</p><p>Brennan F.M., McInnes I.B. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 2008; 118(11):3537-45.</p><p>Dayer J.M., Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford) 2010; 49(1):15-24.</p><p>Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340(6):448-54.</p><p>Woods A., Brull D.J., Humphries S.E., Montgomery H.E. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur Heart J 2000; 21(19):1574-83.</p><p>Rattazzi M., Puato M., Faggin E. et al. C-reactive protein and interleukin-6 in vascular disease: culprits or passive bystanders? J Hypertens 2003;21(10):1787-803.</p><p>Pepys M.B., Hirschfield G.M. C-reactive protein: a critical update. J Clin Invest 2003; 111(12):1805-12.</p><p>Насонов Е.Л., Панюгова Е.В., Александрова Е.Н. С-реактивный белок - маркер воспаления при атеросклерозе (новые данные). Кардиология 2002; 7:53-62.</p><p>Naka T., Nishimoto N., Kishimoto T. The paradigm of IL-6: from basic science to medicine. Arthr Res 2002;4(Suppl. 3): 233-42.</p><p>Heinrich P.C., Behrmann I., Haan S. et al. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003;15(374):1-20.</p><p>Rose-John S., Scheller J., Elson G., Jones S.A. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol 2006;80(2):227-36.</p><p>Насонов Е.Л. Новые возможности фармакотерапии ревматических болезней - ингибирование интерлейкина 6. Клин фармакол тер 2008;17(1):2-8.</p><p>Sack U., Kinne R.W., Marx T. Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. Rheumatol Int 1993;13(2):45-51.</p><p>Madhok R., Crilly A., Watson J. Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis 1993;52(3):232-4.</p><p>Bermudez E.A., Rifai N., Buring J. et al. Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 2002; 22(10):1668-73.</p><p>Fernandez-Real J.M., Vayreda M., Richart C. et al. Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001;86(3):1154-9.</p><p>Brady S.R., de Courten B., Reid C.M. The role of traditional cardiovascular risk factors among patients with rheumatoid arthritis. J Rheumatol 2009;36(1):34-40.</p><p>Dessein P.H., Joffe B.I. Suppression of circulating interleukin-6 concentrations is associated with decreased endothelial activation in rheumatoid arthritis. Clin Exp Rheumatol 2006;24(2):161-7</p><p>Esteve E., Castro A., Lоpez-Bermejo A. et al. Serum interleukin-6 correlates with endothelial dysfunction in healthy men independently of insulin sensitivity. Diabetes Care 2007;30(4):939-45.</p><p>Mahmud A., Feely J. Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension 2005; 46(5):1118-22.</p><p>Salomon R.N., Underwood R., Doyle M.V. et al. Increased apolipoprotein E and c-fms gene expression without elevated interleukin 1 or 6 mRNA levels indicates selective activation of macrophage functions in advanced human atheroma. Proc Natl Acad Sci USA 1992;89(7):2814-8.</p><p>Seino Y., Ikeda U., Ikeda M. Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. Cytokine 1994; 6(1):87-91.</p><p>Koenig W., Khuseyinova N. Biomarkers of atherosclerotic plaque instability and rupture. Arterioscler Thromb Vasc Biol 2007; 1:15-26.</p><p>Danesh J., Kaptoge S., Mann A.G. et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med 2008;5(4):600-10.</p><p>Ridker P.M., Rifai N., Stampfer M.J. et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101(15):1767-72.</p><p>Volpato S., Guralnik J.M., Ferrucci L. et al. Cardiovascular disease, interleukin-6, and risk of mortality in older women: the women's health and aging study. Circulation 2001;103(7):947-53.</p><p>Harris T.B., Ferrucci L., Tracy R.P. et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 1999;106(5):506-12.</p><p>Ridker P.M., Hennekens C.H., Buring J.E. et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;23:342(12):836-43</p><p>Biasucci L.M., Vitelli A., Liuzzo G. et al. Elevated levels of interleukin-6 in unstable angina. Circulation 1996;94(5):874-7.</p><p>Biasucci L.M., Liuzzo G., Fantuzzi G. et al. Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation 1999;99(16):2079-84.</p><p>Cusack M., Odemuyiwa S., Kamalvand K. et al. Can systemic markers of inflammation accurately predict short-term outcome in patients with unstable coronary syndrome? J Amer Coll Cardiol 2001;37(Suppl. A):359A.</p><p>Dinh W., Fü th R., Nickl W. et al. Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders. Cardiovasc Diabetol 2009;12(8):58.</p><p>Whiteley W., Jackson C., Lewis S. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med 2009;6(9):e100014</p><p>Gotsman I., Stabholz A., Planer D. et al. Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden? Isr Med Assoc J 2008;10(7):494-8.</p><p>Schieffer B., Schieffer E., Hilfiker- Kleiner D. et al. Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability. Circulation 2000;101(12):1372-8.</p><p>Funakoshi Y., Ichiki T., Ito K., Takeshita A. Induction of interleukin-6 expression by angiotensin II in rat vascular smooth muscle cells. Hypertension 1999;34(1):118-25.</p><p>Sadoshima J. Cytokine actions of angiotensin II. Circ Res 2000; 86(12):1187-9.</p><p>Suzuki Y., Ruiz-Ortega M., Lorenzo O. Inflammation and angiotensin II. Int J Biochem Cell Biol 2003;35(6):881-900.</p><p>Kuo L.T., Yang N.I., Cherng W.J. Serum interleukin-6 levels, not genotype, correlate with coronary plaque complexity. Int Heart J 2008;49(4):391-402.</p><p>Hoshi T., Kitagawa K., Yamagami H. et al. Relation between interleukin-6 level and subclinical intracranial large-artery atherosclerosis. Atherosclerosis 2008; 197(1):326-32.</p><p>Ingegnoli F., Fantini F., Favalli E.G. et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade. J Autoimmun 2008; 31(2):175-9.</p><p>Oleksowicz L., Mrowiec Z., Zuckerman D. et al. Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism. Thromb Haemost 1994;72(2):302-8.</p><p>Ridker P.M., Cushman M., Stampfer M.J. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336(14):973-9.</p><p>Humphries S.E., Luong L.A., Ogg M.S. et al. The interleukin-6-174G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 2001; 22(24):2243-52.</p><p>Brull D.J., Montgomery H.E., Sanders J. et al. Interleukin-6 gene -174g>c and-572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 2001;21(9):1458-63</p><p>Aker S., Bantis C., Reis P. et al. Influence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients. Nephrol Dial Transplant 2009;24(9):2847-51.</p><p>Gaudino M., Andreotti F., Zamparelli R. et al. The -174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication? Circulation 2003;9;108(Suppl. 1): 195-9.</p><p>Panoulas V.F., Stavropoulos-Kalinoglou A., Metsios G.S. et al. Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking. Atherosclerosis 2009; 204(1):178-83.</p><p>Palomino-Morales R., Gonzalez-Juanatey C., Vazquez-Rodriguez T.R. et al. Interleukin-6 gene -174 promoter polymorphism is associated with endothelial dysfunction but not with disease susceptibility in patients with rheumatoid arthritis. Clin Exp Rheumatol 2009;27(6):964-70.</p><p>Попкова Т.В., Новикова Д.С., Насонов Е.Л. Кардиоваскулярные факторы риска при ревматических заболеваниях: связь с воспалением. Consilium medicum 2010;2:112-8</p><p>Gonzalez-Gay M.A., De Matias J.M., Gonzalez-Juanatey C. et al. Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis. Clin Exp Rheumatol 2006; 24:83-6.</p><p>Fernandez-Real J.M., Vayreda M., Richart C. et al. Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001;86(3):1154-9.</p><p>Bermudez E.A., Rifai N., Buring J. et al. Interrelationships among circulating interleukin-6, C-reactive protein and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 2002; 22:1668-73</p><p>Schillaci G., Pirro M., Gemelli F. et al. Increased C-reactive protein concentrations in never-treated hypertension: the role of systolic and pulse pressures. J Hypertens 2003;21:1841-6.</p><p>Kim K., Lee J.H., Chang H.J. et al. Association between blood pressure variability and inflammatory marker in hypertensive patients. Circ J 2008;72:293-8.</p><p>Panoulas V.F., Douglas K.M., Smith J.P. et al. Galectin-2 (LGALS2) 3279C/T polymorphism may be independently associated with diastolic blood pressure in patients with rheumatoid arthritis. Clin Exp Hypertens 2009;31(2):93-104.</p><p>Vgontzas A.N., Papanicolaou D.A., Bixler E.O. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997;82(5):1313-6.</p><p>Mohamed-Ali V., Goodrick S., Rawesh A. et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997;82(12):4196-200.</p><p>Langenberg C., Bergstrom J., Scheidt-Nave C. et al. Cardiovascular death and the metabolic syndrome: role of adipositysignaling hormones and inflammatory markers. Diabetes Care 2006;29(6):1363-9.</p><p>Libby P., Ridker P.M., Maseri A. Inflammation and atherosclerosis. Circulation 2002;105(9):1135-43.</p><p>Straub R.H., Hense H.W., Andus T. Hormone replacement therapy and interrelation between serum interleukin-6 and body mass index in postmenopausal women: a population-based study. J Clin Endocrinol Metab 2000;85(3):1340-4.</p><p>Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol 2005;78(4):819-35.</p><p>Carey A.L., Febbraio M.A. Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia 2004;47(7):1135-42.</p><p>Rotter V., Nagaev I., Smith U. et al. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overex-pressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003; 278(46):45777-84.</p><p>Kirwan J.P. Insulin sensitivity in skeletal muscle: «use it or lose it, fast». J Appl Physiol 2010;108(5):1023-4.</p><p>Chung C.P., Oeser A., Solus J.F. et al. Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthr Rheum 2008;58(7):2105-12</p><p>Tappia P.S., Troughton K.L., Langley-Evans S.C. et al. Cigarette smoking influences cytokine production and antioxidant defences. Clin Sci (London) 1995; 88(4):485-9.</p><p>Del Ruicon I.D., Williams K., Stern M.P. et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthr Rheum 2001;44(12):2737-45.</p><p>Dessein P.H., Joffe B.I., Veller M.G. et al. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J Rheumatol 2005;32(3):435-42.</p><p>Sattar N., Crompton P., Cherry L. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthr Rheum 2007;56:831-9.</p><p>Попкова Т.В., Новикова Д.С., Новиков А.А. и др. Роль нарушений в системе транспорта холестерина крови в развитии атеросклероза при ревматоидном артрите. Науч-практич ревматол 2007; 5:4-10.</p><p>Nielen M.J., van Halm V.P., Nurmohamed M.T. et al. Rheumatoid arthritis is preceded by a preclinical phase, characterized by increased C-reactive protein levels and a more atherogenic lipid profile. Arthr Rheum 2003;48:344</p><p>Van Halm V.P., Nielen M.J., Nurmohamed M.T. et al. Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Ann Rheum Dis 2006;3:1-5.</p><p>Ettinger W.H., Varma V.K., Sorci-Thomas M. et al. Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb 1994;14(1):8-13.</p><p>Khovidhunkit W., Kim M.S., Memon R.A. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 2004;45:1169-96</p><p>Popa C., Netea M.G., Radstake T.R. et al. Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 2005;64:303-5.</p><p>Peters M.J., Symmons D.P., McCarey D.W. et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis - TASK FORCE «Cardiovascular risk management in RA». Ann Rheum Dis 2010;69(2):325-31.</p><p>Choi E., Sattar N. Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis 2009; 68:460-9.</p><p>Новикова Д.С., Попкова Т.В., Насонов Е.Л. Профилактика сердечно-сосудистых осложнений при ревматоидном артрите. Тер арх 2009;5:88-96.</p><p>Nishimoto N., Yoshizaki K., Miyasaka N. et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthr Rheum 2004; 50:1761-9.</p><p>Sattar N. Effect of tocilizumab treatment on lipid parameters (pooled data: OPTION & TOWARD).</p><p>Maini R.N., Taylor P.C., Szechinski J. et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthr Rheum 2006;54:2817-29.</p><p>Nishimoto N., Hashimoto J., Miyasaka N. et al. Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X-ray reader-blinded randomized controlled trial of tocilizumab. Ann Rheum Dis 2007;66:1162-7.</p><p>Kawashiri S.Y., Kawakami A., Yamasaki S. et al. Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis. Rheumatol Int 2009;Dec 19 [Epub. ahead of print</p><p>Gazi I.F., Boumpas D.T., Mikhailidis D.P. et al. Clustering of cardiovascular risk factors in rheumatoid arthritis: the rationale for using statins. Clin Exp Rheum 2007;25:102-11</p><p>Bisoendial R., Stroes E., Kastelein J., Tak P. Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins. Nat Rev Rheumatol 2010;6:157-64.</p><p>Насонов Е.Л. Перспективы применения статинов в ревматологии. Рус мед журн 2003;11:1273-6.</p><p>Abeles A.M., Pillinger M. Statins as anti-infammatory and immunomodulatory agents. A future in rheumatologic therapy? Arthr Rheum 2006;54:393-407.</p><p>Новикова Д.С., Попкова Т.В., Насонов Е.Л. Снижение кардиоваскулярного риска при ревматоидном артрите: двойная польза статинов. Науч-практич ревматол 2010;6:61-71.</p><p>Lazzerini P.E., Lorenzini S., Selvi E. et al. Simvastatin inhibits cytokine production and nuclear factor-kB activation in interleukin 1ß-stimulated synoviocytes from rheumatoid arthritis patients. Clin Exp Rheum 2007;25:696-700.</p><p>Yokota K., Mioyoshi F., Myazaki K. et al. High concentration simvastatin induces apoptosis in fibroblast-like synoviocytes from patients with rheumatoid arthritis. J Rheumatol 2008;35:193-200.</p></div><br />
The authors declare that there are no conflicts of interest present.