Internal and Emergency Medicine

, Volume 5, Issue 6, pp 495–500 | Cite as

Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psoriatic and rheumatoid arthritis patients

  • Gianluigi Mazzoccoli
  • Incoronata Notarsanto
  • Gennaro Davide de Pinto
  • Mariangela Pia Dagostino
  • Angelo De Cata
  • Giuseppe D’Alessandro
  • Roberto Tarquini
  • Gianluigi Vendemiale
IM - Original

Abstract

For a long time, the endothelial covering of the vessels has been considered an inert surface. On the contrary, the endothelial cells are active and dynamic elements in the interaction between blood and tissues. The control of the vessel basal tone is obtained by the complex balance between the relaxing and contracting endothelial factors. Previous clinical studies show that patients suffering from rheumatoid arthritis and other autoimmune rheumatologic pathologies are at high risk of death being prematurely affected by atherosclerosis and cardiovascular diseases. Blocking tumor necrosis factor (TNF)-α by biological drugs improves the endothelial function. The aim of our study was to evaluate the effects of two anti-TNF-α drugs (infliximab and etanercept) on the endothelial function by evaluating the flow-mediated dilatation (FMD), which was measured in the brachial artery before and after treatment and after 8–12 weeks. We enrolled 36 patients (average age 52 ± 9.8 years, 12 men and 24 women), 25 of them were affected by rheumatoid arthritis (RA) and 11 were affected by psoriatic arthritis (PsA) and they were divided into three groups: 10 patients were treated with etanercept, 13 patients were treated with infliximab, 13 patients were treated with DMARDs. We measured the common carotid intimal-medial thickness (ccIMT) and the endothelial function was evaluated by FMD measurement in the brachial artery, before treatment, 1 h after the beginning of treatment and after 8–12 weeks. No statistically significant difference between the three groups was found for the ultrasonographic evaluation of the carotid IMT. On the contrary, the differences between FMD values before and after the treatment in the patients treated with etanercept (13.1 ± 0.01 vs. 18.8 ± 0.01%, p < 0.01) and in the patients treated with infliximab (11.8 ± 0.09 vs. 16.7 ± 0.09%, p < 0.01) were statistically significant. Long-term evaluation for infliximab and etanercept was performed by comparing the FMD values, respectively, 8 and 12 weeks after the first treatment. After 8 weeks, FMD value was similar to the value recorded at enrollment in the infliximab group (11.9 ± 0.03 vs. 13.54 ± 0.04%, p = 0.236) and the FMD values in the etanercept group after 12 weeks showed a not statistically significant reduction of vasodilatating effect (13.01 ± 0.03 vs. 15.67 ± 0.02%, p = 0.197). In conclusion, the use of biological drugs in patients affected by autoimmune arthritis can modify the endothelial function, as indicated by the induced FMD changes, but the long-term effect tends to be considerably reduced.

Keywords

Flow-mediated dilatation Etanercept Infliximab Autoimmune arthritis 

Notes

Conflict of interest

None.

References

  1. 1.
    Bacon PA, Stevens RJ, Carruthers DM et al (2002) Accelerated atherogenesis in autoimmune rheumatic disease. Autoimmun Rev 1:338–347CrossRefPubMedGoogle Scholar
  2. 2.
    Del Rincon I, Williams K, Stern MP, Freeman GL, Escalante A (2001) High incidence of cardiovascular events in rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 44:2737–2745CrossRefPubMedGoogle Scholar
  3. 3.
    Del Rincon I, Freeman GL, Haas RW, O’Leary DH, Escalante A (2005) Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical manifestations to atherosclerosis. Arthritis Rheum 52:3413–3423CrossRefPubMedGoogle Scholar
  4. 4.
    Agouni A, Lagrue-Lak-Hal AH, Ducluzeau PH, Mostefai HA, Draunet-Busson C, Leftheriotis G, Heymes C, Martinez MC, Andriantsitohaina R (2008) Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. Am J Pathol 173(4):1210–1219CrossRefPubMedGoogle Scholar
  5. 5.
    Lahera V, Goicoechea M, de Vinuesa SG, Miana M, de lasHeras N, Cachofeiro V, Luño J et al (2007) Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis: beneficial effects of statins. Curr Med Chem 14(2):243–248 (review)CrossRefPubMedGoogle Scholar
  6. 6.
    Thanyasiri P, Celermajer DS, Adams MR (2005) Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease. Am J Physiol Heart Circ Physiol 289(2):H513–H517CrossRefPubMedGoogle Scholar
  7. 7.
    Gresele P, Momi S, Migliacci R (2010) Endothelium, venous thromboembolism and ischaemic cardiovascular events. Thromb Haemost 103(1):56–61PubMedGoogle Scholar
  8. 8.
    Ross R (1999) Atherosclerosis: an inflammatory disease. N Engl J Med 340:115–126CrossRefPubMedGoogle Scholar
  9. 9.
    Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA et al (2002) Prognostic value of coronary vascular endothelial dysfunction. Circulation 106:653–658CrossRefPubMedGoogle Scholar
  10. 10.
    Roman MJ, Naqvi TZ, Gardin JM, Gerhard-Herman M, Jaff M, Mohler E (2006) Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology. J Am Soc Echocardiogr 19(8):943–954CrossRefPubMedGoogle Scholar
  11. 11.
    Takase B, Uehata A, Akima T, Nagai T, Nishioka T, Hamabe A, Satomura K, Ohsuzu F, Kurita A (1998) Endothelium-dependent flow mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol 82(12):1535–1539CrossRefPubMedGoogle Scholar
  12. 12.
    Szekanecz Z, Kerekes G, Soltész P (2009) Vascular effects of biologic agents in RA and spondyloarthropathies. Nat Rev Rheumatol 5:677–684CrossRefPubMedGoogle Scholar
  13. 13.
    Kerekes G, Soltész P, Dér H, Veres K, Szabó Z, Végvári A, Shoenfeld Y, Szekanecz Z (2009) Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann N Y Acad Sci 1173:814–821CrossRefPubMedGoogle Scholar
  14. 14.
    Leli C, Pasqualini L, Vaudo G, Gaggioli S, Scarponi AM, Mannarino E (2010) Carotid intima-media thickness and bone turnover: the role of C-terminal telopeptide of type I collagen. Intern Emerg Med 5:127–134CrossRefPubMedGoogle Scholar
  15. 15.
    Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A (2007) Relation between serum uric acid and carotid intima-media thickness in healthy postmenopausal women. Intern Emerg Med 2:19–23CrossRefPubMedGoogle Scholar
  16. 16.
    Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA et al (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilatation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257–265CrossRefPubMedGoogle Scholar
  17. 17.
    Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, Garcia-Porrua C, Llorca J, Vidan J et al (2003) HLA-DRB1 status influences endothelial dysfunction in long-term treated patients with rheumatoid arthritis. Am J Med 114:647–652CrossRefPubMedGoogle Scholar
  18. 18.
    Wong M, Toh L, Wilson A, Rowley K, Karschimkus C, Prior D et al (2003) Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation. Arthritis Rheum 48:81–89CrossRefPubMedGoogle Scholar
  19. 19.
    van Zonneveld AJ, de Boer HC, van der Veer EP, Rabelink TJ (2010) Inflammation, vascular injury and repair in rheumatoid arthritis. Ann Rheum Dis 69:57–60CrossRefGoogle Scholar
  20. 20.
    Foster W, Carruthers D, Lip GYH, Blann AD (2010) Inflammation and microvascular and macrovascular endothelial dysfunction in rheumatoid arthritis: effect of treatment. J Rheumatol 37:711–716CrossRefPubMedGoogle Scholar
  21. 21.
    Smookler DS, Mohammed FF, Kassiri Z, Duncan GS, Mak TW, Khokha R (2006) Cutting edge: tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation. J Immunol 176:721–725PubMedGoogle Scholar
  22. 22.
    Gerard G, Rollins BJ (2001) Chemokines and disease. Nat Immunol 2:108–115CrossRefPubMedGoogle Scholar
  23. 23.
    Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–31CrossRefPubMedGoogle Scholar
  24. 24.
    Szekanecz Z, Kerekes G, Dér H, Sándor Z, Szabó Z, Végvári A, Simkovics E, Soós L, Szentpétery A, Besenyei T, Szücs G, Szántó S, Tamási L, Szegedi G, Shoenfeld Y, Soltész P (2007) Accelerated atherosclerosis in rheumatoid arthritis. Ann N Y Acad Sci 1108:349–358CrossRefPubMedGoogle Scholar
  25. 25.
    Kerekes G, Szekanecz Z, Dér H, Sándor Z, Lakos G, Muszbek L, Csipö I, Sipka S, Seres I, Paragh G, Kappelmayer J, Szomják E, Veres K, Szegedi G, Shoenfeld Y, Soltész P (2008) Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity. J Rheumatol 35:398–406PubMedGoogle Scholar
  26. 26.
    Bergholm R, Leirisalo-Repo M, Vehkavaara S, Makimattila S, Taskinen MR, Yki-Jarvinen H (2002) Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. ArteriosclerThromb Vasc Biol 22(10):1637–1641CrossRefGoogle Scholar
  27. 27.
    Vita JA, Keaney JF Jr (2002) Endothelial function: a barometer for cardiovascular risk? Circulation 106(6):640–642CrossRefPubMedGoogle Scholar
  28. 28.
    Moens AL, Goovaerts I, Claeys MJ, Vrints CJ (2005) Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 127(6):2254–2263 (Review)CrossRefPubMedGoogle Scholar
  29. 29.
    Brady SRE, de Courten B, Reid CM, Cicuttini FM, de Courten MPJ, Liew D (2009) The role of traditional cardiovascular risk factors among patients with rheumatoid arthritis. J Rheumatol 36(1):34–40PubMedGoogle Scholar
  30. 30.
    Maradit-Kremers H, Crowson CS, Nicola PJ et al (2005) Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 52:402–411CrossRefPubMedGoogle Scholar
  31. 31.
    Hamdulay SS, Mason JC (2009) Disease-modifying anti-rheumatic drugs: do they reduce cardiac complications of RA? Heart 18:1471–1472CrossRefGoogle Scholar
  32. 32.
    Hurlimann D, Forster A, Noll G, Enseleit F, Chenevard R, Distler O et al (2002) Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 106:2184–2187CrossRefPubMedGoogle Scholar
  33. 33.
    Kerekes G, Soltész P, Dér H, Veres K, Szabó Z, Végvári A, Szegedi G, Shoenfeld Y, Szekanecz Z (2009) Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. ClinRheumatol. 27:833–839Google Scholar
  34. 34.
    Irace C, Mancuso G, Fiaschi E, Madia A, Sesti G, Gnasso A (2004) Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol. Atherosclerosis 177(1):113–118CrossRefPubMedGoogle Scholar
  35. 35.
    Khan F, Galarraga B, Belch JF (2010) The role of endothelial function and its assessment in rheumatoid arthritis. Nat Rev Rheumatol 6:253–261CrossRefPubMedGoogle Scholar

Copyright information

© SIMI 2010

Authors and Affiliations

  • Gianluigi Mazzoccoli
    • 1
  • Incoronata Notarsanto
    • 1
  • Gennaro Davide de Pinto
    • 1
  • Mariangela Pia Dagostino
    • 1
  • Angelo De Cata
    • 1
  • Giuseppe D’Alessandro
    • 3
  • Roberto Tarquini
    • 4
  • Gianluigi Vendemiale
    • 2
  1. 1.Department of Internal MedicineScientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, Opera di Padre Pio da PietrelcinaS. Giovanni Rotondo (FG)Italy
  2. 2.Geriatrics Unit, Department of Medical SciencesUniversity of FoggiaFoggia (FG)Italy
  3. 3.Department of Internal MedicineUniversity of FoggiaFoggiaItaly
  4. 4.Department of Internal MedicineUniversity of FlorenceFlorenceItaly

Personalised recommendations