Clinical Rheumatology

, Volume 29, Issue 7, pp 763–770 | Cite as

Endothelial dysfunction in ankylosing spondylitis improves after tumor necrosis factor-α blockade

  • Ashit Syngle
  • Kanchan Vohra
  • Anjali Sharma
  • L. Kaur
Original Article

Abstract

Chronic inflammation in ankylosing spondylitis (AS) is associated with vascular endothelial dysfunction. Infliximab improves inflammatory disease activity in AS patients, but its effect on endothelial dysfunction has still not been tested in these patients. Twelve anti-TNF naive AS patients (mean age, 32.6 ± 3.94 years; disease duration, 5.6 ± 0.8 years) with high disease activity [Bath ankylosing spondylitis disease activity index (BASDAI score > 4)] despite treatment with stable doses of conventional disease modifying anti-rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [BASDAI and Bath ankylosing spondylitis functional index (BASFI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels], serum nitrite concentration, and endothelium-dependent and endothelium-independent vasodilation of the brachial artery were measured at baseline and 12 weeks of therapy after single intravenous infusion of infliximab (5 mg/kg). Previous DMARD(s) regimen remained unchanged throughout the study period. After treatment with infliximab, flow-mediated vasodilation improved from 9.81 ± 1.70% to 26.93 ± 2.34% (p < 0.001), whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter (13.65 ± 2.10% versus 14.59 ± 1.93%, p = 0.08, and 4.45 ± 0.15 versus 4.46 ± 0.15 mm, p = 0.3, respectively). Nitrite concentration reduced from 6.50 ± 0.21 to 2.57 ± 0.18 µmol/l (p < 0.001), ESR from 40.90 ± 6.00 to 11.50 ± 1.38 mm in the first hour (p < 0.001), and CRP level from 29.08 ± 4.11 to 2.69 ± 0.43 mg/dl (p < 0.001). BASDAI and BASFI scores were significantly reduced from 5.40 ± 1.14 to 1.40 ± 0.70 (p < 0.05) and 5.05 ± 1.76 to 0.20 ± 0.63 (p < 0.05), respectively. The study suggests that in ankylosing spondylitis, endothelial dysfunction is a part of the disease process and infliximab improves both endothelial dysfunction and inflammatory disease activity.

Keywords

Ankylosing spondylitis Endothelial dysfunction Infliximab 

Notes

Acknowledgments

Support and acknowledgment: None.

Disclosures

None.

References

  1. 1.
    Agarwal V (2010) Spondyloarthropathies. In: Syngle A, Deodhar SD (eds) Rheumatology principles and practice. Jaypee, India, pp 179–189Google Scholar
  2. 2.
    Sari I, Okan T, Akar S, Cece H, Altay C, Secil M, Birlik M et al (2006) Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology 45:283–286CrossRefPubMedGoogle Scholar
  3. 3.
    Lautermann D, Barun J (2002) Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol 20:S11–S15PubMedGoogle Scholar
  4. 4.
    Lehtinen K (1993) Mortality and causes of death in 398 patients admitted with ankylosing spondylitis. Ann Rheum Dis 52:174–176CrossRefPubMedGoogle Scholar
  5. 5.
    Peters MJ, Irene E, Horst-Bruinsma V et al (2004) Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum 34:585–592CrossRefPubMedGoogle Scholar
  6. 6.
    Divecha H, Sattar N, Rumley A, Cherry L, Lowe GDO, Sturrock R (2005) Cardiovascular risk parameters in men with ankylosing spondylitis in comparison with non-inflammatory control subjects: relevance of systemic inflammation. Clin Sci 09:171–176Google Scholar
  7. 7.
    Heeneman S, Daemen MJ (2007) Cardiovascular risks in spondyloarthritides. Curr Opin Rheumatol 19:358–362CrossRefPubMedGoogle Scholar
  8. 8.
    Van Ejick IC, Peters MJL, Seme EH, van der Horst-bruinsma IE, Dijkmans BAC, Smulders YM, Nurmohamed MT (2009) Microvascular function is impaired in ankylosing spondylitis and improves after tumour necrosis factor α blockade. Ann Rheum Dis 66:362–366Google Scholar
  9. 9.
    Gonzalez-Gay MA, Gonzalez Juananey C, Martin J (2005) Rheumatoid arthritis; a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 35:8–17CrossRefPubMedGoogle Scholar
  10. 10.
    Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammantano L, Simantov R et al (2003) Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349:2399–2406CrossRefPubMedGoogle Scholar
  11. 11.
    Poddubnyĭ DA, Rebrov AP (2007) Endothelial dysfunction in patients with Bechterew’s disease (ankylosing spondylitis). Klin Med (Mosk) 85:66–69Google Scholar
  12. 12.
    Bilsborough W, Keen H, Taylor A, O’Driscoll GJ, Arnolda L, Green DJ (2006) Anti tumour necrosis factor-alpha therapy over conventional therapy improves endothelial function in adults with rheumatoid arthritis. Rheumatol Int 26:1125–1131CrossRefPubMedGoogle Scholar
  13. 13.
    Vaudo G, Marchesi S, Gerli R, Allegrucci R, Giordano A, Siepi D et al (2004) Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis 63:31–35CrossRefPubMedGoogle Scholar
  14. 14.
    Davignon J, Ganz P (2004) Role of endothelial dysfunction in atherosclerosis. Circulation 09:III27–32Google Scholar
  15. 15.
    Blake GJ, Ridker PM (2001) Novel clinical markers of vascular wall inflammation. Circ Res 89:763–771CrossRefPubMedGoogle Scholar
  16. 16.
    Hurlimann D, Forster A, Noll G, Enseleit F, Chenevard R, Distler O et al (2002) Anti-tumour necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 106:2184–2187CrossRefPubMedGoogle Scholar
  17. 17.
    Zochling J (2008) Assessment and treatment of ankylosing spondylitis: current status and future directions. Current Opinion in Rheumatology 20:398–403CrossRefPubMedGoogle Scholar
  18. 18.
    Syngle A (2006) Arthritis and its treatment. In: Rattan S, Kassem M (eds) Prevention and treatment of age-related diseases. Springer, the Netherlands, pp 105–32CrossRefGoogle Scholar
  19. 19.
    Braun J, Brandt J, Listing A, Zink R, Alten G, Burmester W, Golder E et al (2003) Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis. Arthritis & Rheumatism 48:2224–2233CrossRefGoogle Scholar
  20. 20.
    Cardillo C, Schinzari F, Mores N et al (2006) Intravascular tumor necrosis factor α blockade reverses endothelial dysfunction in rheumatoid arthritis. Clin Pharmacol Ther 80:275–281CrossRefPubMedGoogle Scholar
  21. 21.
    Booth AD, Jayne DR, Kharbanda RK et al (2004) Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation 109:1718–1723CrossRefPubMedGoogle Scholar
  22. 22.
    Schinzari F, Armuzzi A, De Pascalis B et al (2008) Tumor necrosis factor-α antagonism improves endothelial dysfunction in patients with Crohn’s disease. Clin Pharmacol Ther 83:70–76CrossRefPubMedGoogle Scholar
  23. 23.
    Vander LS, Valkerburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368CrossRefGoogle Scholar
  24. 24.
    Zochling J, Braun J, van der Heijde D (2007) Assessments in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 21:699–712CrossRefGoogle Scholar
  25. 25.
    Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS (2002) Spectrophotometric determination of serum nitrite and nitrate by copper–cadmium alloy. Anal Biochem 306:79–82CrossRefPubMedGoogle Scholar
  26. 26.
    Wanchu A, Khullar M, Sud A, Bambrey P (1999) Nitric oxide production is increased in patients with inflammatory myositis. Nitric oxide 3:454–458CrossRefPubMedGoogle Scholar
  27. 27.
    Himento M, Ishibashi T, Nakano S, Furuya K, Kigoshi T, Uchida K et al (2003) A practical procedure for achieving a steady state of NOx concentration in plasma: with special reference to NOx content of Japanese daily food. Tohoku J Exp Med 199:95–110CrossRefGoogle Scholar
  28. 28.
    Zochling J, Braun J, van der Heijde D (2006) Assessments in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 20:521–537CrossRefGoogle Scholar
  29. 29.
    Karoli NA, Rebrov AP (2007) Vascular wall lesion and disorder of endothelial vasoregulating function in patients with ankylosing spondylitis. Klin Med (Mosk) 85:54–57Google Scholar
  30. 30.
    Caliskan M, Erdogan D, Gullu H et al (2008) Impaired coronary microvascular and left ventricular diastolic functions in patients with ankylosing spondylitis. Atherosclerosis 196:306–312CrossRefPubMedGoogle Scholar
  31. 31.
    Mathieu S, Joly H, Baron G, Tournadre G, Dubost J-J, Ristori JM (2008) Trend towards increased arterial stiffness or intima-media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease. Rheumatology (Oxford) 47:1203–7CrossRefGoogle Scholar
  32. 32.
    Syngle A, Vohra K, Kaur L, Sharma S (2009) Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis. Scand J Rheumatol 38:15–22CrossRefPubMedGoogle Scholar
  33. 33.
    Cardaropoli S, Silvango F, Morra E, Pescarmona GP, Tordos T (2003) Infectious and inflammatory stimuli decrease endothelial nitric oxide synthase activity in vitro. J Hypertens 21:2103–2110CrossRefPubMedGoogle Scholar
  34. 34.
    Yoshizumi M, Perrella MA, Burnett JC Jr, Lee ME (1993) Tumor necrosis factor down regulates an endothelial nitric oxide synthase mRNA by shortening its half life. Circ Res 73:205–209PubMedGoogle Scholar
  35. 35.
    Vita JA, Keaney JF Jr, Larson MG, Keyes MJ, Massaro JM, Lipinska I et al (2004) Brachial artery vasodilator function and systemic inflammation in the Framingham Offspring Study. Circulation 110:3604–3609CrossRefPubMedGoogle Scholar
  36. 36.
    Bergholm R, Leirisalo-Repo M, Vehkavaara S, Mäkimattila S, Taskinen MR, Yki-Järvinen H (2002) Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Arterioscler Thromb Vasc Biol 22:1637–1641CrossRefPubMedGoogle Scholar
  37. 37.
    Koppenol WH et al (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5:834–842CrossRefPubMedGoogle Scholar
  38. 38.
    Sierksma A, van der Gaag MS, Grobbee DE, Hendriks HF (2003) Acute and chronic effects of dinner with alcoholic beverages on nitric oxide metabolites in healthy men. Clin Exp Pharmacol Physiol 30:504–506CrossRefPubMedGoogle Scholar
  39. 39.
    Kumar A, Falodia SK, Shankar S, Grover R, Marwaha V, Aneja R, Srivastava K, Das N (2009) Assessment of serum nitrite as biomarker of disease activity in ankylosing spondylitis. Indian J Rheumatology 4:47–50CrossRefGoogle Scholar
  40. 40.
    Sari I, Kebapcilar L, Alacacioglu A, Bilgir O, Yildiz Y, Taylan A (2009) Increased levels of asymmetric dimethylarginine (ADMA)in patients with ankylosing spondylitis. Inter Med 48:1363–1368CrossRefGoogle Scholar
  41. 41.
    Boger RH (2006) Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond. Ann Med 38:126–136CrossRefPubMedGoogle Scholar
  42. 42.
    Boger RH, Maas R, Schulze F, Schwedhelm E (2005) Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality. Clin Chem Lab Med 43:1124–1129CrossRefPubMedGoogle Scholar
  43. 43.
    Kiortsis DN, Mavridis AK, Filippatos TD, Vasakos S, Nikas SN, Drosos AA (2006) Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis. J Rheumatol 33:921–933PubMedGoogle Scholar
  44. 44.
    Popa C, Netea MG, Radstake T et al (2005) Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis. Ann Rheum Dis 64:303–5CrossRefPubMedGoogle Scholar
  45. 45.
    Farkouh ME, Greenberg JD, Jeger RV, Ramanathan K, Verheugt FW, Chesebro JH et al (2007) Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis 66:764–70CrossRefPubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  • Ashit Syngle
    • 1
    • 2
  • Kanchan Vohra
    • 3
  • Anjali Sharma
    • 3
  • L. Kaur
    • 4
  1. 1.Healing Touch City ClinicChandigarhIndia
  2. 2.Fortis Multispeciality HospitalMohaliIndia
  3. 3.Department of Pharmaceutical Sciences and Drug ResearchPunjabi UniversityPatialaIndia
  4. 4.Prime DiagnosticsChandigarhIndia

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