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Published in: Clinical Rheumatology 7/2010

01-07-2010 | Original Article

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

Authors: Ashit Syngle, Kanchan Vohra, Anjali Sharma, L. Kaur

Published in: Clinical Rheumatology | Issue 7/2010

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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.
Literature
1.
go back to reference Agarwal V (2010) Spondyloarthropathies. In: Syngle A, Deodhar SD (eds) Rheumatology principles and practice. Jaypee, India, pp 179–189 Agarwal V (2010) Spondyloarthropathies. In: Syngle A, Deodhar SD (eds) Rheumatology principles and practice. Jaypee, India, pp 179–189
2.
go back to reference 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 45:283–286CrossRefPubMed 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 45:283–286CrossRefPubMed
3.
go back to reference Lautermann D, Barun J (2002) Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol 20:S11–S15PubMed Lautermann D, Barun J (2002) Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol 20:S11–S15PubMed
4.
go back to reference Lehtinen K (1993) Mortality and causes of death in 398 patients admitted with ankylosing spondylitis. Ann Rheum Dis 52:174–176CrossRefPubMed Lehtinen K (1993) Mortality and causes of death in 398 patients admitted with ankylosing spondylitis. Ann Rheum Dis 52:174–176CrossRefPubMed
5.
go back to reference 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 34:585–592CrossRefPubMed 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 34:585–592CrossRefPubMed
6.
go back to reference 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 09:171–176 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 09:171–176
7.
go back to reference Heeneman S, Daemen MJ (2007) Cardiovascular risks in spondyloarthritides. Curr Opin Rheumatol 19:358–362CrossRefPubMed Heeneman S, Daemen MJ (2007) Cardiovascular risks in spondyloarthritides. Curr Opin Rheumatol 19:358–362CrossRefPubMed
8.
go back to reference 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 66:362–366 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 66:362–366
9.
go back to reference Gonzalez-Gay MA, Gonzalez Juananey C, Martin J (2005) Rheumatoid arthritis; a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 35:8–17CrossRefPubMed Gonzalez-Gay MA, Gonzalez Juananey C, Martin J (2005) Rheumatoid arthritis; a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 35:8–17CrossRefPubMed
10.
go back to reference 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 349:2399–2406CrossRefPubMed 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 349:2399–2406CrossRefPubMed
11.
go back to reference Poddubnyĭ DA, Rebrov AP (2007) Endothelial dysfunction in patients with Bechterew’s disease (ankylosing spondylitis). Klin Med (Mosk) 85:66–69 Poddubnyĭ DA, Rebrov AP (2007) Endothelial dysfunction in patients with Bechterew’s disease (ankylosing spondylitis). Klin Med (Mosk) 85:66–69
12.
go back to reference 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 26:1125–1131CrossRefPubMed 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 26:1125–1131CrossRefPubMed
13.
go back to reference 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 63:31–35CrossRefPubMed 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 63:31–35CrossRefPubMed
14.
go back to reference Davignon J, Ganz P (2004) Role of endothelial dysfunction in atherosclerosis. Circulation 09:III27–32 Davignon J, Ganz P (2004) Role of endothelial dysfunction in atherosclerosis. Circulation 09:III27–32
15.
go back to reference Blake GJ, Ridker PM (2001) Novel clinical markers of vascular wall inflammation. Circ Res 89:763–771CrossRefPubMed Blake GJ, Ridker PM (2001) Novel clinical markers of vascular wall inflammation. Circ Res 89:763–771CrossRefPubMed
16.
go back to reference 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 106:2184–2187CrossRefPubMed 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 106:2184–2187CrossRefPubMed
17.
go back to reference Zochling J (2008) Assessment and treatment of ankylosing spondylitis: current status and future directions. Current Opinion in Rheumatology 20:398–403CrossRefPubMed Zochling J (2008) Assessment and treatment of ankylosing spondylitis: current status and future directions. Current Opinion in Rheumatology 20:398–403CrossRefPubMed
18.
go back to reference Syngle A (2006) Arthritis and its treatment. In: Rattan S, Kassem M (eds) Prevention and treatment of age-related diseases. Springer, the Netherlands, pp 105–32CrossRef Syngle A (2006) Arthritis and its treatment. In: Rattan S, Kassem M (eds) Prevention and treatment of age-related diseases. Springer, the Netherlands, pp 105–32CrossRef
19.
go back to reference 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 48:2224–2233CrossRef 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 48:2224–2233CrossRef
20.
go back to reference Cardillo C, Schinzari F, Mores N et al (2006) Intravascular tumor necrosis factor α blockade reverses endothelial dysfunction in rheumatoid arthritis. Clin Pharmacol Ther 80:275–281CrossRefPubMed Cardillo C, Schinzari F, Mores N et al (2006) Intravascular tumor necrosis factor α blockade reverses endothelial dysfunction in rheumatoid arthritis. Clin Pharmacol Ther 80:275–281CrossRefPubMed
21.
go back to reference Booth AD, Jayne DR, Kharbanda RK et al (2004) Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation 109:1718–1723CrossRefPubMed Booth AD, Jayne DR, Kharbanda RK et al (2004) Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation 109:1718–1723CrossRefPubMed
22.
go back to reference 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 83:70–76CrossRefPubMed 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 83:70–76CrossRefPubMed
23.
go back to reference 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 27:361–368CrossRef 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 27:361–368CrossRef
24.
go back to reference Zochling J, Braun J, van der Heijde D (2007) Assessments in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 21:699–712CrossRef Zochling J, Braun J, van der Heijde D (2007) Assessments in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 21:699–712CrossRef
25.
go back to reference Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS (2002) Spectrophotometric determination of serum nitrite and nitrate by copper–cadmium alloy. Anal Biochem 306:79–82CrossRefPubMed Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS (2002) Spectrophotometric determination of serum nitrite and nitrate by copper–cadmium alloy. Anal Biochem 306:79–82CrossRefPubMed
26.
go back to reference Wanchu A, Khullar M, Sud A, Bambrey P (1999) Nitric oxide production is increased in patients with inflammatory myositis. Nitric oxide 3:454–458CrossRefPubMed Wanchu A, Khullar M, Sud A, Bambrey P (1999) Nitric oxide production is increased in patients with inflammatory myositis. Nitric oxide 3:454–458CrossRefPubMed
27.
go back to reference Himento M, Ishibashi T, Nakano S, Furuya K, Kigoshi T, Uchida K et al (2003) A practical procedure for achieving a steady state of NO x concentration in plasma: with special reference to NO x content of Japanese daily food. Tohoku J Exp Med 199:95–110CrossRef Himento M, Ishibashi T, Nakano S, Furuya K, Kigoshi T, Uchida K et al (2003) A practical procedure for achieving a steady state of NO x concentration in plasma: with special reference to NO x content of Japanese daily food. Tohoku J Exp Med 199:95–110CrossRef
28.
go back to reference Zochling J, Braun J, van der Heijde D (2006) Assessments in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 20:521–537CrossRef Zochling J, Braun J, van der Heijde D (2006) Assessments in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 20:521–537CrossRef
29.
go back to reference Karoli NA, Rebrov AP (2007) Vascular wall lesion and disorder of endothelial vasoregulating function in patients with ankylosing spondylitis. Klin Med (Mosk) 85:54–57 Karoli NA, Rebrov AP (2007) Vascular wall lesion and disorder of endothelial vasoregulating function in patients with ankylosing spondylitis. Klin Med (Mosk) 85:54–57
30.
go back to reference Caliskan M, Erdogan D, Gullu H et al (2008) Impaired coronary microvascular and left ventricular diastolic functions in patients with ankylosing spondylitis. Atherosclerosis 196:306–312CrossRefPubMed Caliskan M, Erdogan D, Gullu H et al (2008) Impaired coronary microvascular and left ventricular diastolic functions in patients with ankylosing spondylitis. Atherosclerosis 196:306–312CrossRefPubMed
31.
go back to reference 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) 47:1203–7CrossRef 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) 47:1203–7CrossRef
32.
go back to reference Syngle A, Vohra K, Kaur L, Sharma S (2009) Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis. Scand J Rheumatol 38:15–22CrossRefPubMed Syngle A, Vohra K, Kaur L, Sharma S (2009) Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis. Scand J Rheumatol 38:15–22CrossRefPubMed
33.
go back to reference 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 21:2103–2110CrossRefPubMed 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 21:2103–2110CrossRefPubMed
34.
go back to reference 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 73:205–209PubMed 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 73:205–209PubMed
35.
go back to reference 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 110:3604–3609CrossRefPubMed 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 110:3604–3609CrossRefPubMed
36.
go back to reference 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 22:1637–1641CrossRefPubMed 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 22:1637–1641CrossRefPubMed
37.
go back to reference Koppenol WH et al (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5:834–842CrossRefPubMed Koppenol WH et al (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5:834–842CrossRefPubMed
38.
go back to reference 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 30:504–506CrossRefPubMed 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 30:504–506CrossRefPubMed
39.
go back to reference 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 4:47–50CrossRef 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 4:47–50CrossRef
40.
go back to reference 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 48:1363–1368CrossRef 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 48:1363–1368CrossRef
41.
go back to reference Boger RH (2006) Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond. Ann Med 38:126–136CrossRefPubMed Boger RH (2006) Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond. Ann Med 38:126–136CrossRefPubMed
42.
go back to reference 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 43:1124–1129CrossRefPubMed 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 43:1124–1129CrossRefPubMed
43.
go back to reference 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 33:921–933PubMed 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 33:921–933PubMed
44.
go back to reference 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 64:303–5CrossRefPubMed 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 64:303–5CrossRefPubMed
45.
go back to reference 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 66:764–70CrossRefPubMed 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 66:764–70CrossRefPubMed
Metadata
Title
Endothelial dysfunction in ankylosing spondylitis improves after tumor necrosis factor-α blockade
Authors
Ashit Syngle
Kanchan Vohra
Anjali Sharma
L. Kaur
Publication date
01-07-2010
Publisher
Springer-Verlag
Published in
Clinical Rheumatology / Issue 7/2010
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-010-1402-x

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