CardioSomaticsCardioSomaticsCardioСоматика2221-71852658-5707Eco-Vector4595210.26442/CS45952ArticlesСтатьиReview ArticleSystemic inflammation as a risk factor for cardiovascular disease: review of the literatureСистемное воспаление как фактор риска сердечно-сосудистых заболеваний: обзор литературыMarusenkoI. MМарусенкоИрина Михайловна

проф. каф. госпитальной терапии

imarusenko@yandex.ruPolskayaI. IПольскаяИрина Игоревна

канд. мед. наук, доц. каф. госпитальной терапии

irina_polskaya82@mail.ruPetrozavodsk State UniversityФГБОУ ВО ПетрГУ1503201891VOL 9, NO1 (2018)ТОМ 9, №1 (2018)404625092020Copyright ©; 2018, Eco-VectorCopyright ©; 2018, ООО "Эко-Вектор"2018Eco-VectorООО "Эко-Вектор"https://creativecommons.org/licenses/by-nc-sa/4.0https://cardiosomatics.ru/2221-7185/article/view/45952

The review shows the problem of systemic inflammation as a key factor influencing the cardiovascular morbidity and mortality in patients with autoimmune rheumatic diseases. Represented literature data on the role of inflammation in the pathophysiology of cardiovascular disease in rheumatoid arthritis, its impact on the accelerated development of atherosclerosis. A separate section is devoted to the problem of lipid paradox. Review shows data on the influence of the traditional basic anti-inflammatory drugs and genetically engineered biological agents on the risk of cardiovascular disease in rheumatoid arthritis. Also, EULAR recommendations for assessing the risk of cardiovascular disease in rheumatoid arthritis.

В обзоре рассматривается проблема системного воспаления как ключевого фактора, влияющего на сердечно-сосудистую заболеваемость и смертность у пациентов с аутоиммунными ревматическими заболеваниями. Представлены литературные данные о роли воспаления в патофизиологии сердечно-сосудистых заболеваний при ревматоидном артрите, его влиянии на ускоренное развитие атеросклероза. Отдельный раздел посвящен проблеме липидного парадокса. Представлены данные о влиянии традиционных базисных противовоспалительных препаратов и генно-инженерных биологических препаратов на риск сердечно-сосудистых заболеваний при ревматоидном артрите, а также рекомендации EULAR по оценке риска сердечно-сосудистых заболеваний при ревматоидном артрите.

rheumatoid arthritissystemic inflammationlipid paradoxthe risk of cardiovascular eventsatherosclerosisревматоидный артритсистемное воспалениелипидный парадоксриск сердечно-сосудистых катастрофатеросклерозPeters M.J, Symmons D.P, McCarey D et al. EULARevidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010; 69: 325-31.Solomon D.H, Karlson E.W, Rimm E.B et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 2003; 107: 1303-7.De Groot L, Posthumus M.D, Kallenberg C.G, Bijl M. Risk factors and early detection of atherosclerosis in rheumatoid arthritis. Eur J Clin Invest 2010; 40: 835-42.Gullick N.J, Scott D.L. Co-morbidities in established rheumatoid arthritis. Best Pract Res Clin Rheumatol 2011; 25: 469-83.Meune C, Touze E, Trinquart L, Allanore Y. High risk of clinical cardiovascular events in rheumatoid arthritis: levels of associations of myocardial infarction and stroke through a systematic review and meta-analysis. Arch Cardiovasc Dis 2010; 103: 253-61.Gremese E, Ferraccioli G. The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular risk. Autoimmun Rev 2011; 10: 582-9.Gabriel S.E. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am J Med 2008; 121 (Suppl. 1): S9-14.Peters M.J, van Halm V.P, Voskuyl A.E et al. Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study. Arthritis Rheum 2009; 61: 1571-9.Lindhardsen J, Ahlehoff O, Gislason G.H et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis 2011; 70: 929-34.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: 435-42.Boyer J.F, Gourraud P.A, Cantagrel A et al. Traditional cardiovascular risk factors in rheumatoid arthritis: a meta-analysis. Joint Bone Spine 2011; 78: 179-83.Ku I.A, Imboden J.B, Hsue P.Y, Ganz P. Rheumatoid arthritis: model of systemic inflammation driving atherosclerosis. Circ J 2009; 73: 977-85.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-421.Myasoedova E, Crowson C.S, Kremers H.M 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: 482-7.Steiner G, Urowitz M.B. Lipid profiles in patients with rheumatoid arthritis: mechanisms and the impact of treatment. Semin Arthritis Rheum 2009; 38: 372-81.Peters M.J, Vis M, van Halm V.P et al. Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arthritis. Ann Rheum Dis 2007; 66: 958-61.Schimmel E.K, Yazici Y. Increased lipid levels but unchanged atherogenic index in rheumatoid arthritis patients treated with biologic disease modifying antirheumatic drugs: published experience. Clin Exp Rheumatol 2009; 27: 446-51.Gossec L, Salejan F, Nataf H et al. Challenges of cardiovascular risk assessment in the routine rheumatology outpatient setting: an observational study of 110 rheumatoid arthritis patients. Arthritis Care Res 2013; 65: 712-7.Jellinger P.S, Smith D.A, Mehta A.E et al. American Association of Clinical Endocrinologists' guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract 2012; 18: 1-78.Libby P, Ridker P.M, Hansson G.K. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473: 317-25.Hansson G.K, Hermansson A. The immune system in atherosclerosis. Nat Immunol 2011; 12: 204-12.Innala L, Moller B, Ljung L et al. Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study. Arthritis Res Ther 2011; 13: R131.Book C, Saxne T, Jacobsson L.T. Prediction of mortality in rheumatoid arthritis based on disease activity markers. J Rheumatol 2005; 32: 430-4.Crilly M.A, Kumar V, Clark H.J et al. Arterial stiffness and cumulative inflammatory burden in rheumatoid arthritis: a dose-response relationship independent of established cardiovascular risk factors. Rheumatology 2009; 48: 1606-12.Graf J, Scherzer R, Grunfeld C, Imboden J. Levels of C-reactive protein associated with high and very high cardiovascular risk are prevalent in patients with rheumatoid arthritis. PLoS One 2009; 4: e6242.Del Rincon I, Freeman G.L, Haas R.W et al. Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical manifestations to atherosclerosis. Arthritis Rheum 2005; 52: 3413-23.Gonzalez-Gay M.A, Gonzalez-Juanatey C, Pineiro A et al. High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatol 2005; 32: 1219-23.Maradit-Kremers H, Nicola P.J, Crowson C.S et al. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum 2005; 52: 722-32.Wallberg-Jonsson S, Johansson H, Ohman M.L, Rantapaa-Dahlqvist S. Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onset. J Rheumatol 1999; 26: 2562-71.Crowson C.S, Gabriel S.E. Towards improving cardiovascular risk management in patients with rheumatoid arthritis: the need for accurate risk assessment. Ann Rheum Dis 2011; 70: 719-21.Dessein P.H, Semb A.G. Could cardiovascular disease risk stratification and management in rheumatoid arthritis be enhanced? Ann Rheum Dis 2013; 72: 1743-6.Arts E.E, Popa C, Den Broeder A.A et al. Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis. Ann Rheum Dis 2014, Jan 3. DOI: 10.1136/annrheumdis-2013-204024Danesh 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: e78.Kaptoge S, Di Angelantonio E, Lowe G et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375: 132-40.Danesh J, Lewington S, Thompson S.G et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005; 294: 1799-809.Schultz O, Oberhauser F, Saech J et al. Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein(a) levels in human subjects with rheumatoid diseases. PLoS One 2010; 5: e14328.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. Arthritis Rheum 2008; 58: 2105-12.Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med 2008; 121 (Suppl. 1): S21-31.Kaltsonoudis E, Papagoras C, Drosos A.A. Current and future role of methotrexate in the therapeutic armamentarium for rheumatoid arthritis. Int J Clin Rheumatol 2012; 7: 179-89.Saiki O, Takao R, Naruse Y et al. Infliximab but not methotrexate induces extra-high levels of VLDL-triglyceride in patients with rheumatoid arthritis. J Rheumatol 2007; 34: 1997-2004.Navarro-Millan I, Charles-Schoeman C, Yang S et al. Changes in lipoproteins associated with methotrexate or combination therapy in early rheumatoid arthritis: results from the treatment of early rheumatoid arthritis trial. Arthritis Rheum 2013; 65: 1430-8.Miller A.M, McInnes I.B. Cytokines as therapeutic targets to reduce cardiovascular risk in chronic inflammation. Curr Pharm Des 2011; 17: 1-8.Rho Y.H, Chung C.P, Oeser A et al. Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum 2009; 61: 1580-5.Robertson J, Peters M.J, McInnes I.B, Sattar N. Changes in lipid levels with inflammation and therapy in RA: a maturing paradigm. Nat Rev Rheumatol 2013; 9: 513-23.Ridker P.M, Buring J.E, Shih J et al. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998; 98: 731-3.Del Rincon I, Williams K, Stern M.P et al. Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 2003; 48: 1833-40.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: 2079-84.Ridker P.M, Rifai N, Stampfer M.J, Hennekens C.H. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101: 1767-72.IL6R Genetics Consortium Emerging Risk Factors Collaboration, Sarwar N, Butterworth A.S et al. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet 2012; 379: 1205-13.Choy 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.Marik P.E. Dyslipidemia in the critically ill. Crit Care Clin 2006; 22: 151-9, viii.Vermont C.L, den Brinker M, Kakeci N et al. Serum lipids and disease severity in children with severe meningococcal sepsis. Crit Care Med 2005; 33: 1610-5.Alexopoulos C.G, Pournaras S, Vaslamatzis M et al. Changes in serum lipids and lipoproteins in cancer patients during chemotherapy. Cancer Chemother Pharmacol 1992; 30: 412-6.Watson W.C, Buchanan K.D, Dickson C. Serum cholesterol levels after myocardial infarction. Br Med J 1963; 2: 709-12.MBewu A.D, Durrington P.N, Bulleid S, Mackness M.I. The immediate effect of streptokinase on serum lipoprotein(a) concentration and the effect of myocardial infarction on serum lipoprotein(a), apolipoproteins A1 and B, lipids and C-reactive protein. Atherosclerosis 1993; 103: 65-71.Akgun S, Ertel N.H, Mosenthal A, Oser W. Postsurgical reduction of serum lipoproteins: interleukin-6 and the acute-phase response. J Lab Clin Med 1998; 131: 103-8.Daien C.I, Duny Y, Barnetche T et al. Effect of TNF inhibitors on lipid profile in rheumatoid arthritis: a systematic review with meta-analysis. Ann Rheum Dis 2012; 71: 862-8.Singh U, Dasu M.R, Yancey P.G et al. Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats. J Lipid Res 2008; 49: 1015-23.Wang X, Liao D, Bharadwaj U et al. C-reactive protein inhibits cholesterol efflux from human macrophage-derived foam cells. Arterioscler Thromb Vasc Biol 2008; 28: 519-26.Berrougui H, Momo C.N, Khalil A. Health benefits of high-density lipoproteins in preventing cardiovascular diseases. J Clin Lipidol 2012; 6: 524-33.Charles-Schoeman C, Lee Y.Y, Grijalva V. et al. Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis. Ann Rheum Dis 2012; 71: 1157-62.Van Lenten B.J, Hama S.Y, de Beer F.C et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest 1995; 96: 2758-67.Raterman H.G, Levels H, Voskuyl A.E et al. HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab. Ann Rheum Dis 2013; 72: 560-5.Jamnitski A, Levels J.H, van den Oever I.A, Nurmohamed MT. High-density lipoprotein profiling changes in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: a cohort study. J Rheumatol 2013; 40: 825-30.Schwartz G.G, Olsson A.G, Abt M et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012; 367: 2089-99.Zhao L, Jin W, Rader D et al. A translational medicine perspective of the development of torcetrapib: does the failure of torcetrapib development cast a shadow on future development of lipid modifying agents, HDL elevation strategies or CETP as a viable molecular target for atherosclerosis? A case study of the use of biomarkers and translational medicine in atherosclerosis drug discovery and development. Biochem Pharmacol 2009; 78: 315-25.Van Halm V.P, Nurmohamed M.T, Twisk J.W et al. Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. Arthritis Res Ther 2006; 8: R151.Smolen J.S, Landewe R, Breedveld F.C et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010; 69: 964-75.Westlake S.L, Colebatch A.N, Baird J et al. The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology 2010; 49: 295-307.Choi H.K, Hernan M.A, Seeger J.D et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359: 1173-7.Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 2009; 68: 1100-4.Schiff M.H, Kremer J.M, Jahreis A. et al. Integrated safety in tocilizumab clinical trials. Arthritis Res Ther 2011; 13: R141.Tracey D, Klareskog L, Sasso E.H et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008; 117: 244-79.Stagakis I, Bertsias G, Karvounaris S et al. Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther 2012; 14: R141.Wijbrandts C.A, van Leuven S.I, Boom H.D et al. Sustained changes in lipid profile and macrophage migration inhibitory factor levels after anti-tumour necrosis factor therapy in rheumatoid arthritis. Ann Rheum Dis 2009; 68: 1316-21.Sattar N, Crompton P, Cherry L et al. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthritis Rheum 2007; 56: 831-9.Van Sijl A.M, Peters M.J, Knol D.L et al. The effect of TNF-alpha blocking therapy on lipid levels in rheumatoid arthritis: a meta-analysis. Semin Arthritis Rheum 2011; 41: 393-400.Curtis J.R, John A, Baser O. Dyslipidemia and changes in lipid profiles associated with rheumatoid arthritis and initiation of anti-TNF therapy. Arthritis Care Res 2012; 64: 1282-91.Popa C, Netea M.G, Radstake T et al. Influence of antitumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis. Ann Rheum Dis 2005; 64: 303-5.Westlake S.L, Colebatch A.N, Baird J et al. Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology 2011; 50: 518-31.Barnabe C, Martin B.J, Ghali W.A. Systematic review and meta-analysis: anti-tumor necrosis factor alpha therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res 2011; 63: 522-9.Wong M, Oakley S.P, Young L et al. Infliximab improves vascular stiffness in patients with rheumatoid arthritis. Ann Rheum Dis 2009; 68: 1277-84.Hurlimann D, Forster A, Noll G et al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 2002; 106: 2184-7.McKellar G.E, McCarey D.W, Sattar N, McInnes IB. Role for TNF in atherosclerosis? Lessons from autoimmune disease. Nat Rev Cardiol 2009; 6: 410-7.Del Porto F, Lagana B, Lai S et al. Response to antitumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis. Rheumatology 2007; 46: 1111-5.Emery P, Keystone E, Tony H.P et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to antitumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008; 67: 1516-23.Jones G. The AMBITION trial: tocilizumab monotherapy for rheumatoid arthritis. Expert Rev Clin Immunol 2010; 6: 189-95.Genovese M.C, McKay J.D, Nasonov E.L et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 2008; 58: 2968-80.Greenberg J.D, Kremer J.M, Curtis J.R et al. Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis.Kremer J.M, Blanco R, Brzosko M et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum 2011; 63: 609-21.Smolen J.S, Beaulieu A, Rubbert-Roth A et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008; 371: 987-97.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. Arthritis Rheum 2006; 54: 2817-29.Nishimoto N, Ito K, Takagi N. Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five long-term extensions. Mod Rheumatol 2010; 20: 222-32.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 2011; 31: 451-6.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 randomised controlled trial of tocilizumab. Ann Rheum Dis 2007; 66: 1162-7.Natarajan S, Glick H, Criqui M. et al. Cholesterol measures to identify and treat individuals at risk for coronary heart disease. Am J Prev Med 2003; 25: 50-7.Kannel W.B. Risk stratification of dyslipidemia: insights from the Framingham Study. Curr Med Chem Cardiovasc Hematol Agents 2005; 3: 187-93.Yusuf S, Hawken S, Ounpuu S. et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-52.Sniderman A.D, Jungner I, Holme I et al. Errors that result from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to identify the lipoprotein-related risk of vascular disease. J Intern Med 2006; 259: 455-61.Gabay C, Emery P, van Vollenhoven R. et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 2013; 381: 1541-50.Semb A.G, Kvien T.K, Aastveit A.H et al. Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study. Ann Rheum Dis 2010; 69: 1996-2001.Holmqvist M.E, Wedren S, Jacobsson L.T et al. No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis: results from two Swedish population-based rheumatoid arthritis cohorts. Arthritis Rheum 2009; 60: 2861-9.Holmqvist M.E, Wedren S, Jacobsson L.T et al. Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J Intern Med 2010; 268: 578-85.Sodergren A, Karp K, Boman K et al. Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness. Arthritis Res Ther 2010; 12: R158.