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Rheumatoid arthritis is sufficient to cause atheromatosis but not arterial stiffness or hypertrophy in the absence of classical cardiovascular risk factors

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Abstract

Rheumatoid arthritis (RA) associates with increased cardiovascular disease (CVD) mortality thought to be due to accelerated arterial disease. Different components of arterial disease, namely, atheromatosis, arteriosclerosis, and arterial wall hypertrophy, are differentially affected by classical CVD risk factors, which are highly prevalent in these patients. We hypothesized that RA disease per se may also differentially affect these components. Of 267 consecutive RA patients, we selected specifically those who were free of established CVD and CVD risk factors (18 %); of them, 41 patients (36 women, 49 ± 13 years) could be matched effectively 1:1 for age and gender to healthy controls. Atheromatosis was assessed by the presence of carotid and/or femoral artery plaques, arteriosclerosis by pulse wave velocity and local wall elasticity, and arterial hypertrophy by intima-media thickness and cross-sectional area. More patients had atheromatic plaques than controls (29 vs. 12 %, p = 0.039), and multiarterial atheromatosis was more prevalent in RA (22 vs. 2 %, p = 0.026). Accelerated atheromatosis was not associated with rheumatoid factor, or anti-cyclic citrullinated peptide (CCP) autoantibody status. Plaque burden in patients with less than 5 years disease duration (aged 41 ± 13 years) was comparable to their matched controls. In contrast, all indices of arterial stiffness and hypertrophy were similar between controls and RA patients, even in those with long-standing disease. RA per se is sufficient to cause atheromatosis in the absence of classical CVD risk factors, but has minimal, if any, effect on arteriosclerosis and arterial wall hypertrophy.

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References

  1. Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK, McInnes IB, Haentzschel H, Gonzalez-Gay MA, Provan S, Semb A, Sidiropoulos P, Kitas G, Smulders YM, Soubrier M, Szekanecz Z, Sattar N, Nurmohamed MT (2010) EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 69:325–331

    Article  CAS  PubMed  Google Scholar 

  2. Chung CP, Avalos I, Raggi P, Stein CM (2007) Atherosclerosis and inflammation: insights from rheumatoid arthritis. Clin Rheumatol 26(8):1228–1233

    Article  PubMed  Google Scholar 

  3. Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D (2012) Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis 71:1524–1529

    Article  PubMed  Google Scholar 

  4. Pasceri V, Yeh ET (1999) A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 100:2124–2126

    Article  CAS  PubMed  Google Scholar 

  5. Stevens RJ, Douglas KM, Saratzis AN, Kitas GD (2005) Inflammation and atherosclerosis in rheumatoid arthritis. Expert Rev Mol Med 7:1–24

    Article  PubMed  Google Scholar 

  6. Bamias G, Stamatelopoulos K, Zampeli E, Protogerou A, Sigala F, Papamichael C, Christopoulos P, Kitas GD, Sfikakis PP (2013) Circulating levels of TNF-like cytokine 1A correlate with the progression of atheromatous lesions in patients with rheumatoid arthritis. Clin Immunol 147:144–150

    Article  CAS  PubMed  Google Scholar 

  7. Boyer JF, Gourraud PA, Cantagrel A, Davignon JL, Constantin A (2011) Traditional cardiovascular risk factors in rheumatoid arthritis: a meta-analysis. Joint Bone Spine 78:179–183

    Article  PubMed  Google Scholar 

  8. Protogerou AD, Panagiotakos DB, Zampeli E, Argyris AA, Arida K, Konstantonis GD, Pitsavos C, Kitas GD, Sfikakis PP (2013) Arterial hypertension assessed “out-of-office” in a contemporary cohort of rheumatoid arthritis patients free of cardiovascular disease is characterized by high prevalence, low awareness, poor control and increased vascular damage-associated “white coat” phenomenon. Arthritis Res Ther 15:R142

    Article  PubMed Central  PubMed  Google Scholar 

  9. del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A (2001) High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 44:2737–2745

    Article  PubMed  Google Scholar 

  10. Solomon DH, Kremer J, Curtis JR, Hochberg MC, Reed G, Tsao P, Farkouh ME, Setoguchi S, Greenberg JD (2010) Explaining the cardiovascular risk associated with rheumatoid arthritis: traditional risk factors versus markers of rheumatoid arthritis severity. Ann Rheum Dis 69:1920–1925

    Article  PubMed Central  PubMed  Google Scholar 

  11. Kitas GD, Gabriel SE (2011) Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis 70:8–14

    Article  PubMed  Google Scholar 

  12. Stamatelopoulos KS, Kitas GD, Papamichael CM, Chryssohoou E, Kyrkou K, Georgiopoulos G, Protogerou A, Panoulas VF, Sandoo A, Tentolouris N, Mavrikakis M, Sfikakis PP (2009) Atherosclerosis in rheumatoid arthritis versus diabetes: a comparative study. Arterioscler Thromb Vasc Biol 29:1702–1708

    Article  CAS  PubMed  Google Scholar 

  13. Protogerou A, Zampeli E, Tentolouris N, Makrilakis K, Kitas G, Sfikakis PP (2012) Subclinical femoral atheromatosis in rheumatoid arthritis: comparable prevalence to diabetes mellitus in a case-control study. Ann Rheum Dis 71:1534–1536

    Article  PubMed  Google Scholar 

  14. Cecelja M, Chowienczyk P (2009) Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: a systematic review. Hypertension 54:1328–1336

    Article  CAS  PubMed  Google Scholar 

  15. Wilkinson IB, McEniery CM, Cockcroft JR (2009) Arteriosclerosis and atherosclerosis: guilty by association. Hypertension 54:1213–1215

    Article  CAS  PubMed  Google Scholar 

  16. Roman MJ, Devereux RB, Schwartz JE, Lockshin MD, Paget SA, Davis A, Crow MK, Sammaritano L, Levine DM, Shankar BA, Moeller E, Salmon JE (2005) Arterial stiffness in chronic inflammatory diseases. Hypertension 46:194–199

    Article  CAS  PubMed  Google Scholar 

  17. Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD, Sammaritano L, Devereux RB, Schwartz JE, Levine DM, Salmon JE (2006) Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med 144:249–256

    Article  PubMed  Google Scholar 

  18. Mäki-Petäjä KM, Hall FC, Booth AD, Wallace SM, Yasmin, Bearcroft PW, Harish S, Furlong A, McEniery CM, Brown J, Wilkinson IB (2006) Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-alpha therapy. Circulation 114:1185–1192

    Article  PubMed  Google Scholar 

  19. Schott LL, Kao AH, Cunningham A, Wildman RP, Kuller LH, Sutton-Tyrrell K, Wasko MC (2009) Do carotid artery diameters manifest early evidence of atherosclerosis in women with rheumatoid arthritis? J Womens Health (Larchmt) 18:21–29

    Article  Google Scholar 

  20. Gonzalez-Juanatey C, Llorca J, Martin J, Gonzalez-Gay MA (2009) Carotid intima-media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis. Semin Arthritis Rheum 38:366–371

    Article  PubMed  Google Scholar 

  21. Stamatelopoulos KS, Kitas GD, Papamichael CM, Kyrkou K, Zampeli E, Fragiadaki K, Panoulas VF, Mavrikakis M, Sfikakis PP (2010) Subclinical peripheral arterial disease in rheumatoid arthritis. Atherosclerosis 212:305–309

    Article  CAS  PubMed  Google Scholar 

  22. Kobayashi H, Giles JT, Polak JF, Blumenthal RS, Leffell MS, Szklo M, Petri M, Gelber AC, Post W, Bathon JM (2010) Increased prevalence of carotid artery atherosclerosis in rheumatoid arthritis is artery-specific. J Rheumatol 37:730–739

    Article  PubMed  Google Scholar 

  23. Giles JT, Post WS, Blumenthal RS, Polak J, Petri M, Gelber AC, Szklo M, Bathon JM (2011) Longitudinal predictors of progression of carotid atherosclerosis in rheumatoid arthritis. Arthritis Rheum 63:3216–3225

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Lee JH, Cho KI, Kim SM (2012) Carotid arterial stiffness in patients with rheumatoid arthritis assessed by speckle tracking strain imaging: its association with carotid atherosclerosis. Clin Exp Rheumatol 30:720–728

    PubMed  Google Scholar 

  25. Prevoo ML, van ’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48

    Article  CAS  PubMed  Google Scholar 

  26. Bruce B, Fries JF (2003) The Stanford health assessment questionnaire: dimensions and practical applications. Health Qual Life Outcomes 1:20

    Article  PubMed Central  PubMed  Google Scholar 

  27. Schiffrin EL, Hayoz D (1997) How to assess vascular remodelling in small and medium-sized muscular arteries in humans. J Hypertens 15:571–584

    Article  CAS  PubMed  Google Scholar 

  28. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H (2006) European network for non-invasive investigation of large arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27:2588–2605

    Article  PubMed  Google Scholar 

  29. Corrales A, González-Juanatey C, Peiró ME, Blanco R, Llorca J, González-Gay MA (2014) Carotid ultrasound is useful for the cardiovascular risk stratification of patients with rheumatoid arthritis: results of a population-based study. Ann Rheum Dis 73:722–727

    Article  PubMed  Google Scholar 

  30. van Sijl AM, Peters MJ, Knol DK, de Vet HC, Gonzalez-Gay MA, Smulders YM, Dijkmans BA, Nurmohamed MT (2011) Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum 40:389–397

    Article  PubMed  Google Scholar 

  31. Wong M, Oakley SP, Young L, Jiang BY, Wierzbicki A, Panayi G, Chowienczyk P, Kirkham B (2009) Infliximab improves vascular stiffness in patients with rheumatoid arthritis. Ann Rheum Dis 68:1277–1284

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Vassilopoulos D, Gravos A, Vlachopoulos C, Kandili A, Ioakeimidis N, Pectasides D, Stefanadis C (2014) Adalimumab decreases aortic stiffness independently of its effect in disease activity in patients with rheumatoid arthritis. Clin Rheumatol

  33. Mäki-Petäjä KM, Elkhawad M, Cheriyan J, Joshi FR, Ostör AJ, Hall FC, Rudd JH, Wilkinson IB (2012) Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation 126:2473–2480

    Article  PubMed  Google Scholar 

  34. Protogerou AD, Zampeli E, Fragiadaki K, Stamatelopoulos K, Papamichael C, Sfikakis PP (2011) A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis. Atherosclerosis 219:734–736

    Article  CAS  PubMed  Google Scholar 

  35. Mazzoccoli G, Notarsanto I, de Pinto GD, Dagostino MP, De Cata A, D’Alessandro G, Tarquini R, Vendemiale G (2010) Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psoriatic and rheumatoid arthritis patients. Intern Emerg Med 5:495–500

    Article  PubMed  Google Scholar 

  36. Hürlimann D, Forster A, Noll G, Enseleit F, Chenevard R, Distler O, Béchir M, Spieker LE, Neidhart M, Michel BA, Gay RE, Lüscher TF, Gay S, Ruschitzka F (2002) Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 106:2184–2187

    Article  PubMed  Google Scholar 

  37. Del Porto F, Laganà B, Lai S, Nofroni I, Tinti F, Vitale M, Podestà E, Mitterhofer AP, D’Amelio R (2007) Response to anti-tumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis. Rheumatology (Oxford) 46:1111–1115

    Article  Google Scholar 

  38. Ferrante A, Giardina AR, Ciccia F, Parrinello G, Licata G, Avellone G, Giardina E, Impastato R, Triolo G (2009) Long-term anti-tumour necrosis factor therapy reverses the progression of carotid intima-media thickness in female patients with active rheumatoid arthritis. Rheumatol Int 30:193–198

    Article  CAS  PubMed  Google Scholar 

  39. Protogerou AD, Kitas GD, Sfikakis PP (2012) Importance of standardized methodology to comparisons between studies of rheumatoid arthritis and cardiovascular disease: comment on the article by Giles et al. Arthritis Rheum 64:3487–3488, author reply 3488

    Article  PubMed  Google Scholar 

  40. Zhang J, Chen L, Delzell E, Muntner P, Hillegass WB, Safford MM, Millan IY, Crowson CS, Curtis JR (2014) The association between inflammatory markers, serum lipids and the risk of cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 73:1301–1308

    Article  CAS  PubMed  Google Scholar 

  41. Yasmin, McEniery CM, Wallace S, Mackenzie IS, Cockcroft JR, Wilkinson IB (2004) C-reactive protein is associated with arterial stiffness in apparently healthy individuals. Arterioscler Thromb Vasc Biol 24:969–974

    Article  CAS  PubMed  Google Scholar 

  42. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874

    Article  CAS  PubMed  Google Scholar 

  43. Stoll G, Bendszus M (2006) Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 37:1923–1932

    Article  CAS  PubMed  Google Scholar 

  44. Zampeli E, Protogerou A, Stamatelopoulos K, Fragiadaki K, Katsiari CG, Kyrkou K, Papamichael CM, Mavrikakis M, Nightingale P, Kitas GD, Sfikakis PP (2012) Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: a longitudinal study. Arthritis Res Ther 14:R44

    Article  PubMed Central  PubMed  Google Scholar 

  45. Sandoo A, van Zanten JJ V, Metsios GS, Carroll D, Kitas GD (2011) Vascular function and morphology in rheumatoid arthritis: a systematic review. Rheumatology (Oxford) 50:2125–2139

    Article  Google Scholar 

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Financial support

The study was supported by the Athens University Medical School grant ELKE 097.

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Authors and Affiliations

  1. First Department of Propaedeutic Internal Medicine, Laikon Hospital, Athens University Medical School, Ag Thoma, 17, 11527, Athens, Greece

    Aikaterini Arida, Evi Zampeli, George Konstantonis, Kalliope Fragiadaki, Athanasios D. Protogerou & Petros P. Sfikakis

  2. Department of Rheumatology, Dudley Group NHS Foundation Trust, Dudley, UK

    George D. Kitas

  3. Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK

    George D. Kitas

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  1. Aikaterini Arida
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  2. Evi Zampeli
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  4. Kalliope Fragiadaki
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  5. George D. Kitas
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  6. Athanasios D. Protogerou
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  7. Petros P. Sfikakis
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Correspondence to Petros P. Sfikakis.

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Arida, A., Zampeli, E., Konstantonis, G. et al. Rheumatoid arthritis is sufficient to cause atheromatosis but not arterial stiffness or hypertrophy in the absence of classical cardiovascular risk factors. Clin Rheumatol 34, 853–859 (2015). https://doi.org/10.1007/s10067-015-2914-1

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  • DOI: https://doi.org/10.1007/s10067-015-2914-1

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