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Relationship of serum osteoprotegerin with arterial stiffness, preclinical atherosclerosis, and disease activity in patients with ankylosing spondylitis

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Abstract

Patients with ankylosing spondylitis (AS) reportedly have a higher mortality and morbidity risk. Osteoprotegerin (OPG) was recently defined as an important cardiovascular (CV) marker in the general population. We aimed to assess the relationship of serum OPG levels with arterial stiffness, carotid intima media thickness (CIMT), and clinical and laboratory data in AS patients. We examined 60 AS patients without CV disease or risk factors and 50 healthy controls. Disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), whereas functional capacity was evaluated using the Bath Ankylosing Spondylitis Functional Index (BASFI). Serum OPG levels were measured with the enzyme-linked immunosorbent assay. Carotid-femoral pulse wave velocity (PWV) was used as an indicator of arterial stiffness, whereas CIMT (examined via carotid ultrasonography) was used to evaluate preclinical atherosclerosis. The mean serum OPG level, PWV, and CIMT were significantly higher in AS patients than in controls (106.7 ± 50.9 vs. 58.1 ± 12.7 pg/mL; 7.4 ± 1.8 vs. 6.2 ± 1.2 m/s; 0.72 ± 0.13 vs. 0.57 ± 0.07 mm, respectively; P < 0.001 for all). In AS patients, the serum OPG levels were not significantly correlated with PWV and CIMT but were significantly correlated with erthrocyte sedimentation rate, BASFI, and ASDAS. AS patients without CV disease or risk exhibited high OPG levels and increased PWV and CIMT values. Although OPG levels were not significantly correlated with PWV or CIMT, future long-term follow-up studies will help define the predictive value of OPG in these patients.

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References

  1. Choe JY, Lee MY, Rheem I, Rhee MY, Park SH, Kim SK (2008) No differences of carotid intima-media thickness between young patients with ankylosing spondylitis and healthy controls. Joint Bone Spine 75:548–553

    Article  CAS  PubMed  Google Scholar 

  2. Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK et al (2010) EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 69(2):325–331

    Article  CAS  PubMed  Google Scholar 

  3. John H, Kitas G (2012) Inflammatory arthritis as a novel risk factor for cardiovascular disease. Eur J Int Med 23:575–579

    Article  Google Scholar 

  4. Tyrrell PN, Beyene J, Feldman BM, McCrindle BW, Silverman ED, Bradley TJ (2010) Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol 30(5):1014–1026

    Article  CAS  PubMed  Google Scholar 

  5. Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Martin J, Llorca J (2008) Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum 38(2):67–70

    Article  PubMed  Google Scholar 

  6. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Colloborative Research Group. N Engl J Med 340:14–22

    Article  PubMed  Google Scholar 

  7. Mathieu S, Joly H, Baron G, Tournadre A, Dubost JJ, Ristori JM, Lusson JR, Soubrier M (2008) Trend towards increased arterial stiffness or intima-media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease. Rheumatology 47:1203–1207

    Article  CAS  PubMed  Google Scholar 

  8. Venuraju SM, Yerramasu A, Corder R, Lahiri A (2010) Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol 55(19):2049–2061

    Article  CAS  PubMed  Google Scholar 

  9. Van Campenhout A, Golledge J (2009) Osteoprotegerin, vascular calcification and atherosclerosis. Atherosclerosis 204(2):321–329

    Article  PubMed  Google Scholar 

  10. Asanuma YF, Shimada Y, Kouzu N, Yokota K, Nakajima K, Sato K, Akiyama Y, Isozaki M, Mikami AS, Kobayashi H, Mimura T (2013) Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis. Mod Rheumatol 23(2):269–275

    Article  CAS  PubMed  Google Scholar 

  11. Hofbauer LC, Schoppet M (2004) Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292:490–495

    Article  CAS  PubMed  Google Scholar 

  12. Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, Nishizawa Y (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106:1192–1194

    Article  CAS  PubMed  Google Scholar 

  13. Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC (2003) Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 88:1024–1028

    Article  CAS  PubMed  Google Scholar 

  14. Rhee EJ, Lee WY, Kim SY, Kim BJ, Sung KC, Kim BS, Kang JH, Oh KW, Oh ES, Baek KH, Kang MI, Woo HY, Park HS, Kim SW, Lee MH, Park JR (2005) Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein. Clin Sci 108:237–243, Lond

    Article  CAS  PubMed  Google Scholar 

  15. Hosbond SE, Poulsen TS, Diederichsen AC, Nybo M, Rasmussen LM, Mickley H (2012) Osteoprotegerin as a marker of atherosclerosis: a systematic update. Scand Cardiovasc J 46(4):203–211

    Article  CAS  PubMed  Google Scholar 

  16. Van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368

    Article  PubMed  Google Scholar 

  17. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21:2286–2291

    CAS  PubMed  Google Scholar 

  18. Machado P, Landewé R, Lie E, Kvien TK, Braun J, Baker D, van der Heijde D (2011) Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis 70:47–53

    Article  PubMed  Google Scholar 

  19. Calin A, Garrett S, Whitelock H, Kennedy LG, O’Hea J, Mallorie P, Jenkinson T (1994) A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 21:2281–2285

    CAS  PubMed  Google Scholar 

  20. Kiechl S, Werner P, Knoflach M, Furtner M, Willeit J, Schett G (2006) The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease. Expert Rev Cardiovasc Ther 4(6):801–811

    Article  CAS  PubMed  Google Scholar 

  21. Grisar J, Bernecker PM, Aringer M, Redlich K, Sedlak M, Wolozcszuk W, Spitzauer S, Grampp S, Kainberger F, Ebner W, Smolen JS, Pietschmann P (2002) Ankylosing spondylitis, psoriatic arthritis, and reactive arthritis show increased bone resorption, but differ with regard to bone formation. J Rheumatol 29:1430–1436

    PubMed  Google Scholar 

  22. Chen CH, Chen HA, Liao HT, Liu CH, Tsai CY, Chou CT (2010) Soluble receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical mobility and reflects systemic inflammation. Clin Rheumatol 29(10):1155–1161

    Article  PubMed  Google Scholar 

  23. Kwon SR, Lim MJ, Suh CH, Park SG, Hong YS, Yoon BY, Kim HA, Choi HJ, Park W (2012) Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy. Rheumatol Int 32(8):2523–2527

    Article  CAS  PubMed  Google Scholar 

  24. Sveaas SH, Berg IJ, Provan SA, Semb AG, Olsen IC, Ueland T, Aukrust P, Vøllestad N, Hagen KB, Kvien TK, Dagfinrud H (2015) Circulating levels of inflammatory cytokines and cytokine receptors in patients with ankylosing spondylitis: a cross-sectional comparative study. Scand J Rheumatol 44(2):118–124

    Article  CAS  PubMed  Google Scholar 

  25. Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, Santer P, Smolen J, Poewe W, Willeit J (2004) Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 109(18):2175–2180

    Article  CAS  PubMed  Google Scholar 

  26. Genre F, López-Mejías R, Miranda-Filloy JA, Ubilla B, Carnero-López B, Palmou-Fontana N, Gómez-Acebo I, Blanco R, Rueda-Gotor J, Pina T, González-Juanatey C, Llorca J, González-Gay MÁ (2014) Osteoprotegerin correlates with disease activity and endothelial activation in non-diabetic ankylosing spondylitis patients undergoing TNF-α antagonist therapy. Clin Exp Rheumatol 32(5):640–646

    PubMed  Google Scholar 

  27. Asanuma Y, Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM (2007) Serum osteoprotegerin is increased and independently associated with coronary-artery atherosclerosis in patients with rheumatoid arthritis. Atherosclerosis 135–41

  28. Dessein PH, López-Mejias R, González-Juanatey C, Genre F, Miranda-Filloy JA, Llorca J, González-Gay MA (2014) Independent relationship of osteoprotegerin concentrations with endothelial activation and carotid atherosclerosis in patients with severe rheumatoid arthritis. J Rheumatol 41(3):429–436

    Article  CAS  PubMed  Google Scholar 

  29. Nurhamed MT, van der Horst-Bruinsma, Maksymowych WP (2012) Cardiovascular and cerebrovascular diseases in ankylosing spondylitis: current insights. Curr Rheumatol Rep 14:415–421

    Article  Google Scholar 

  30. Peters MJ, van Eijk IC, Smulders YM, Serne E, Dijkmans BA, van der Horst-Bruinsma IE, Nurmohamed MT (2010) Signs of accelerated preclinical atherosclerosis in patients with ankylosing spondylitis. J Rheumatol 37(1):161–166

    Article  PubMed  Google Scholar 

  31. Bodnár N, Kerekes G, Seres I, Paragh G, Kappelmayer J, Némethné ZG, Szegedi G, Shoenfeld Y, Sipka S, Soltész P, Szekanecz Z, Szántó S (2011) Assessment of subclinical vascular disease associated with ankylosing spondylitis. J Rheumatol 38(4):723–729

    Article  PubMed  Google Scholar 

  32. Hamdi W, Chelli Bouaziz M, Zouch I, Ghannouchi MM, Haouel M, Ladeb MF, Kchir MM (2012) Assessment of preclinical atherosclerosis in patients with ankylosing spondylitis. J Rheumatol 39(2):322–326

    Article  CAS  PubMed  Google Scholar 

  33. Chen Y, Chung HY, Zhao CT, Wong A, Zhen Z, Tsang HH, Lau CS, Tse HF, Yiu KH (2015) Left ventricular myocardial dysfunction and premature atherosclerosis in patients with axial spondyloarthritis. Rheumatology (Oxford) 54(2):292–301

    Article  Google Scholar 

  34. Gonzalez-Jaunatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Dierssen T, Vaqueiro I, Blanco R, Martin J, Llorca J, Gonzalaez-Gay MA (2009) The high prevalence of subclinical atherosclerosis in patients with ankylosing spondylitis without clinically evident cardiovascular disease. Medicine (Baltimore) 88(6):358–365

    Article  Google Scholar 

  35. Berg IJ, Semb AG, van der Heijde D, Kvien TK, Olsen IC, Dagfinrud H, Provan SA (2015) CRP and ASDAS are associated with future elevated arterial stiffness, a risk marker of cardiovascular disease, in patients with ankylosing spondylitis: results after 5-year follow-up. Ann Rheum Dis 74(8):1562–1566

    Article  PubMed  Google Scholar 

  36. Jain S, Khera R, Corrales-Medina VF, Townsend RR, Chirinos JA (2014) Inflammation and arterial stiffness in humans. Atherosclerosis 237(2):381–390

    Article  CAS  PubMed  Google Scholar 

  37. Capkın E, Kiriş A, Karkucak M, Durmuş I, Gökmen F, Cansu A, Tosun M, Ayar A (2011) Investigation of effects of different treatment modalities on structural and functional vessel wall properties in patients with ankylosing spondylitis. Joint Bone Spine 78:378–382

    Article  PubMed  Google Scholar 

  38. Berg IJ, van der Heijde D, Dagfinrud H, Seljeflot I, Olsen IC, Kvien TK, Semb AG, Provan SA (2015) Disease activity in ankylosing spondylitis and associations to markers of vascular pathology and traditional cardiovascular disease risk factors: a cross-sectional study. J Rheumatol 42(4):645–653

    Article  CAS  PubMed  Google Scholar 

  39. Capkın E, Karkucak M, Kiriş A, Durmuş I, Karaman K, Karaca A, Tosun M, Ayar A (2012) Anti-TNF-α therapy may not improve arterial stiffness in patients with AS: a 24-week follow-up. Rheumatology 51:910–914

    Article  PubMed  Google Scholar 

  40. Mathieu S, Pereira B, Couderc M, Rabois E, Dubost JJ, Soubrier M (2013) No significant changes in arterial stiffness in patients with ankylosing spondylitis after tumour necrosis factor alpha blockade treatment for 6 and 12 months. Rheumatology 52:204–209

    Article  CAS  PubMed  Google Scholar 

  41. Angel K, Provan A, Gulseth HL, Mowinckel P, Kristian TK, Atar D (2010) Tumor Necrosis factor-α antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study. Hypertension 55:333–338

    Article  CAS  PubMed  Google Scholar 

  42. Taylan A, Sari I, Akinci B, Bilge S, Kozaci D, Akar S, Colak A, Yalcin H, Gunay N, Akkoc N (2012) Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis. BMC Musculoskelet Disord 13:191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

    Münevver Serdaroğlu Beyazal, Aysegül Kücükali Türkyılmaz & Gül Devrimsel

  2. Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Kliniği, Recep Tayyip Erdoğan Üniversitesi, 53100, Rize, Turkey

    Münevver Serdaroğlu Beyazal

  3. Department of Cardiology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

    Turan Erdoğan & Ismail Sahin

  4. Department of Biochemistry, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

    Medine Cumhur Cüre

  5. Department of Radiology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

    Mehmet Beyazal

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  1. Münevver Serdaroğlu Beyazal
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Serdaroğlu Beyazal, M., Erdoğan, T., Türkyılmaz, A.K. et al. Relationship of serum osteoprotegerin with arterial stiffness, preclinical atherosclerosis, and disease activity in patients with ankylosing spondylitis. Clin Rheumatol 35, 2235–2241 (2016). https://doi.org/10.1007/s10067-016-3198-9

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