Skip to main content
SpringerLink
Log in

Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Enhanced cardiovascular risk in ankylosing spondylitis (AS) provides a strong rationale for early therapeutical intervention. In view of the proven benefit of statins in atherosclerotic vascular disease, we aimed to investigate the effect of rosuvastatin on endothelial dysfunction (ED) and inflammatory disease activity in AS. In a single-blind, placebo-controlled, parallel study, 32 AS patients were randomized to receive 24 weeks of treatment with rosuvastatin (10 mg/day, n = 17) and placebo (n = 15) as an adjunct to existing stable antirheumatic drugs. Flow-mediated dilatation (FMD) was assessed by AngioDefender™ (Everest Genomic Ann Arbor, USA). Inflammatory measures (BASDAI, BASFI, CRP and ESR) and pro-inflammatory cytokines (tumour necrosis factor-alpha [TNF-α], interleukin-6 [IL-6] and interleukin-1 [IL-1]) were measured at baseline and after treatment. Lipids and adhesion molecules (intracellular adhesion molecule [ICAM-1] and vascular cell adhesion molecule [VCAM-1]) were estimated at baseline and after treatment. At baseline, inflammatory measures, pro inflammatory cytokines and adhesion molecules were elevated among both groups. After treatment with rosuvastatin, FMD improved significantly (p < 0.01). Levels of inflammatory measures, TNF-α, IL-6 and ICAM-1 decreased significantly (p < 0.01) after treatment with rosuvastatin. Rosuvastatin exerted positive effect on lipid spectrum. No significant change in the placebo group. Significant negative correlation was observed between FMD and IL-6, ICAM-1, CRP after treatment with rosuvastatin. First study to show that rosuvastatin improves inflammatory disease activity and ED in AS. Rosuvastatin lowers the proinflammatory cytokines, especially IL-6 and TNF-α, which downregulates adhesion molecules and CRP production which in turns improves ED. Improvement in ED in AS occurs through both cholesterol-independent and cholesterol-dependent pathways. Rosuvastatin can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation of AS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lautermann D, Braun J (2002) Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol 20:S11–S15

    CAS  PubMed  Google Scholar 

  2. Divecha H, Sattar N, Rumley A, Cherry L, Lowe GD, Sturrock R (2005) Cardiovascular risk parameters in men with ankylosing spondylitis in comparison with non-inflammatory control subjects: relevance of systemic inflammation. Clin Sci (Lond) 109:171–176

    Article  CAS  Google Scholar 

  3. Heeneman S, Daemen MJ (2007) Cardiovascular risks in spondyloarthritides. Curr Opin Rheumatol 19:358–362

    Article  PubMed  Google Scholar 

  4. Abou-Raya A, Abou-Raya S (2006) Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. Autoimmun Rev 5:331–337

    Article  CAS  PubMed  Google Scholar 

  5. Vaudo G, Marchesi S, Gerli R, Allegrucci R, Giordano A, Siepi D, Pirro M, Shoenfeld Y, Schillaci G, Mannarino E (2004) Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis 63:31–35

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. 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 26:1125–1131

    Article  CAS  PubMed  Google Scholar 

  7. Scandinavian Simvastatin Survival Study Group (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389

    Google Scholar 

  8. Heart Protection Study Collaborative Group (2002) MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 360:7–22

    Article  Google Scholar 

  9. Jain MK, Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4:977–987

    Article  CAS  PubMed  Google Scholar 

  10. Greenwood J, Mason JC (2007) Statins and the vascular endothelial inflammatory response. Trends Immunol 28:1–19

    Article  CAS  Google Scholar 

  11. Kaisa M, Mäki-Petäjä KM, Booth AD, Hall FC, Wallace SML, Brown J, McEniery CM, Wilkinson IB (2007) Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol 50:852–858

    Article  Google Scholar 

  12. Tan KCB, Chow WS, Tam VHG et al (2002) Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilatation in type 2 diabetes mellitus. J Clin Endocrinol Metab 87:563–568

    Article  CAS  PubMed  Google Scholar 

  13. Marchesi S, Lupattelli G, Siepi D et al (2000) Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women. J Cardiovasc Pharmacol 36:617–621

    Article  CAS  PubMed  Google Scholar 

  14. Timár O, Szekanecz Z, Kerekes G et al (2013) Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis—a prospective case-series study. Arthritis Res Ther 15:1–9

    Article  Google Scholar 

  15. Vander 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  CAS  Google Scholar 

  16. Garrett S, Jenkinson T, Kennedy LG et al (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 

  17. Calin A, Garrett S, Whitelock H et al (1996) A new approach to defining functional ability in ankylosing spondylitis: the development of the bath ankylosing spondylitis functional index. J Rheumatol 21:2281–2285

    Google Scholar 

  18. Sari I, Okan T, Akar S et al (2006) Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology 45:283–286

    Article  CAS  PubMed  Google Scholar 

  19. 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

    Google Scholar 

  20. 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 34:585–592

    Article  PubMed  Google Scholar 

  21. Caliskan M, Erdogan D, Gullu H et al (2008) Impaired coronary microvascular and left ventricular diastolic functions in patients with ankylosing spondylitis. Atherosclerosis 196:306–312

    Article  CAS  PubMed  Google Scholar 

  22. 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) 47:1203–1207

    Article  CAS  Google Scholar 

  23. Syngle A, Vohra K, Kaur L, Sharma S (2009) Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis. Scand J Rheumatol 38:15–22

    Article  CAS  PubMed  Google Scholar 

  24. Syngle A, Vohra k, Sharma A, Kaur L (2010) Endothelial dysfunction in ankylosing spondylitis improves after tumor necrosis factor-alpha blockade. Clin Rheumatol 29:763–770

    Article  PubMed  Google Scholar 

  25. Ferreira GA, Navarro TP, Telles RW, Andrade LEC, Sato EI (2007) Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial. Rheumatology 46:1560–1565

    Article  CAS  PubMed  Google Scholar 

  26. Tikiz C, Utuk O, Pirildar T et al (2005) Effects of angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with long term rheumatoid arthritis. J Rheumatol 32:2095–2101

    CAS  PubMed  Google Scholar 

  27. Ii M, Losordo DW (2007) Statins and the endothelium. Vascul Pharmacol 46:1–9

    Article  CAS  PubMed  Google Scholar 

  28. van Denderen JC, Peters MJL, van Halm VP, van der Horst-Bruinsma IE, Dijkmans BAC, Nurmohamed MT (2006) Statin therapy might be beneficial for patients with ankylosing spondylitis. Ann Rheum Dis 65:695–696

    Article  PubMed Central  PubMed  Google Scholar 

  29. McCarey DW, McInnes IB, Madhok R et al (2004) Trial of atorvastatin in rheumatoid arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 363:2015–2021

    Article  CAS  PubMed  Google Scholar 

  30. Holschermann H, Schuster D, Parviz B, Haberbosch W, Tillmanns H, Muth H (2006) Statins prevent NF-kappa B transactivation independently of the IKK-pathway in human endothelial cells. Atherosclerosis 185:240–245

    Article  PubMed  Google Scholar 

  31. van Halm VP, van Denderen JC, Peters MJL et al (2006) Increased disease activity is associated with a deteriorated lipid profile in patients with ankylosing spondylitis. Ann Rheum Dis 65:1473–1477

    Article  PubMed Central  PubMed  Google Scholar 

  32. Cui Y, Blumenthal RS, Flaws JA et al (2001) Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med 161:1413–1419

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by University Grant Commission, New Delhi, India, [F.No. 41-725/2012 (SR)] for providing the grant to conduct this study.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, Punjab, India

    Nidhi Garg & Pawan Krishan

  2. Cardio Rheuma & Healing Touch City Clinic, Chandigarh and Fortis Multi Speciality Hospital, Mohali, India

    Ashit Syngle

Authors
  1. Nidhi Garg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pawan Krishan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashit Syngle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashit Syngle.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garg, N., Krishan, P. & Syngle, A. Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis. Clin Rheumatol 34, 1065–1071 (2015). https://doi.org/10.1007/s10067-015-2912-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-015-2912-3

Keywords

Search

Navigation