Substantiation of necessity and evaluation of endothelial dysfunction correction efficiency in patients with ankylosing spondylitis
- State Pedagogical University «Ternopil State Medical University named after I.Ya. Gorbachevsky Ministry of Health of Ukraine»
Summary. Background. In recent years, sufficient data has been accumulated about the important role of the persistent inflammatory process in inflammatory diseases of the joints in the occurrence of cardiovascular diseases due to the development of endothelial dysfunction, and in the future — atherosclerosis, remodeling of the vascular wall and myocardium. Today, there is little doubt: cardiovascular events are the main cause of the fact that the level of adverse, life-threatening conditions in arthritis and spondylarthritis is much higher than that of general population. It is known that imbalance of nitric oxide production plays one of the leading roles in the pathogenesis of vascular remodeling, and there is a possibility that correction of this link in the early stages of development will prevent endothelial dysfunction (ED). Objective — to determine the prevalence of ED in patients with ankylosing spondylitis (AS) and to evaluate the effectiveness of the combined use of L-arginine for its correction. Materials and methods. The study included 110 patients. In all of them, along with the protocol examination, endothelium-dependent vasodilation (EDVD) in response to reactive hyperemia was evaluated according to the method first described by D.S. Celermajer. In order to correct ED, we have used 100 ml of 4.2% solution of a nitric oxide donor, L-arginine amino acid, as intravenous infusions followed by continued oral therapy for 1 month. Results. Reduced EDVD (<10%) was detected among patients with AS in 63.7% of cases, and the probable dependence of this quantitative index on the degree of inflammation and dyslipidemia was established. After the treatment, an increase was noted in the quantitative value of the EDVD indicator by 23.2% (p10%), endothelium state improved significantly compared to the baseline level (8.5%<EDVD<10.0%) in 20 (50%) patients, and only 3 (7.5%) patients did not report any significant changes (EDVD<8.5%) (p<0.05). Conclusions. The performed studies can confirm the significant prevalence of ED in patients with AS. The use of L-arginine in the comprehensive treatment of AS patients for 10 days with subsequent continuation of oral administration for another 1 month can significantly reduce the manifestations of ED.
Key words: ankylosing spondylitis, endothelial dysfunction, L-arginine.
- Altaany Z., Moccia F., Munaron L. et al. (2014) Hydrogen sulfide and endothelial dysfunction: relationship with nitric oxide. Curr. Med. Chem., 21(32): 3646–3661.
- Ben Assayag E., Shenhar-Tsarfaty S., Bova I. et al. (2009) Association of the –757T>C polymorphism in the CRP gene with circulating C-reactive protein levels and carotid atherosclerosis. Thromb. Res., 124(4): 458–462.
- Braun J., Sieper J. (2007) Ankylosing spondylitis. Lancet, 369: 1379–1390.
- Brown M.A., Kenna T., Wordsworth B.P. (2016) Genetics of ankylosing spondylitis-insights into pathogenesis. Nat. Rev. Rheumatol., 12: 81–91.
- Celermajer D.S., Sorensen K.E., Gooch V.M. et al. (1992) Noninvasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 340: 1111–1115.
- Chen H.A., Chen С.H., Liao H.T. et al. (2012) Clinical, functional, and radiographic differences among juvenileonset, adultonset, and late-onset ankylosing spondylitis. J. Rheumatol., 39(5): 1013–1038.
- Deyab G., Hokstad I., Whist J.E. et al. (2017) Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis. Arthritis Res. Ther., 17, 19(1): 232.
- Donald J.A., Forgan L.G., Cameron M.S. (2015) The evolution of nitric oxide signalling in vertebrate blood vessels. J. Comp. Physiol. B., 185(2): 153–171.
- Heeneman S. (2007) Cardiovascular risks in spondyloarthritites. Curr. Opin. Rheumatol., 19: 358–362.
- Kumar A., Falodia S.K., Shankar S. et al. (2009) Assessment of serum nitrite as biomarker of disease activity in ankylosing spondylitis. Indian J. Rheumatology, 4: 47–50.
- Mehta A., Patel J., Al Rifai M. et al. (2018) Inflammation and coronary artery calcification in South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Atherosclerosis, 29(270): 49–56.
- Parrinello C.M., Lutsey P.L., Ballantyne C.M. et al. (2015) Six-year change in high-sensitivity C-reactive protein and risk of diabetes, cardiovascular disease, and mortality. Am. Heart J., 170(2): 380–389.
- Paulo M., Banin T.M., de Andrade F.A., Bendhack L.M. (2014) Enhancing vascular relaxing effects of nitric oxide-donor ruthenium complexes. Future Med. Chem., 6(7): 825–838.
- Sarojini A., Sai Ravi Shanker A., Anitha M. (2013) Inflammatory Markers-Serum Level of C-Reactive Protein, Tumor Necrotic Factor-α, and Interleukin-6 as Predictors of Outcome for Peripartum Cardiomyopathy. J. Obstet. Gynaecol. India, 63(4): 234–239.
- Smith J.A. (2015) Update on ankylosing spondylitis: current concepts in pathogenesis. Curr. Allergy Asthma Rep., 15(1): 489.
- Syngle A., Vohra K., Sharma A., Kaur L. (2010) Endothelial dysfunction in ankylosing spondylitis improves after tumor necrosis factor-α Clin. Rheumatol., 29: 763–770.
- Taurog J.D., Chhabbra A., Colbert R.A. (2016) Axial spondyloarthritis and ankylosing spondylitis. New Engl. J. Med., 26: 2563–2574.
- Teupser D., Weber O., Rao T.N. et al. (2011) No reduction of atherosclerosis in C-reactive protein (CRP)-deficient mice. J. Biol. Chem., 286(8): 6272–6279.
- van der Heijde D., Ramiro S., Landewé R. et al. (2017) 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann. Rheum. Dis., 76(6): 978–991.
- Verma I., Syngle A., Krishan P., Garg N. (2017) Endothelial Progenitor Cells as a Marker of Endothelial Dysfunction and Atherosclerosis in Ankylosing Spondylitis: A Cross-Sectional Study. Int. J. Angiol., 26(1): 36–42.
- Whayne T.F. (2018) Non-traditional Cardiovascular Risk Markers in the Era of Established Major Risk Factors and Multiple Guidelines. Curr. Vasc. Pharmacol., Jan. 22 [Epub. ahead of print].
- Zhao Y., Vanhoutte P.M., Leung S.W. (2015) Vascular nitric oxide: Beyond eNOS. J. Pharmacol. Sci., 129(2): 83–94.