Plasma Homocysteine Concentrations In Patients With Rheumatoid Arthritis

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In this study, we investigated the concentration of serum homocysteine (Hcy) in patients with rheumatoid arthritis (RA) compared with the control group and the connection between homocysteine and parameters of inflammation and disease activity. Sixty RA patients and 20 healthy controls were included in the study, and clinical examination and investigation were performed during which disease activity was assessed. Peripheral blood samples were used for all of the assays. Levels of Hcy were 33% higher in the RA patients than in the control subjects (mean +/− SD 11.79±3.72 μmol/L versus 8.90±1.38 μmol/L; p< 0.01). A significant correlation was found between parameters of inflammation (C-reactive protein) and homocysteine in patients (r=0.322, p=0.012). Patients with high disease activity had a significantly greater increase in homocysteine (p<0.05). An increase in plasma homocysteine in RA patients is related to the parameters of inflammation and disease activity. Elevated Hcy levels occur commonly in patients with RA and may explain some of the increased cardiovascular mortality seen in RA patients.

1. Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010; 69(2): 312-325.

2. Martin-Martinez MA, Gonzalez-Juanatey C, Castaneda S, Llorca J, et al. Recommendations for the management of cardiovascular risk in patients with rheumatoid arthritis: scientific evidence and expert opinion. Semin Arthritis Rheum. 2014; 44(1): 1-8.

3. Borman P, Taşbaş O, Karabulut H, Tukun A, Yorgancıoğlu R. Thymidylate synthase genetic polymorphism and plasma total homocysteine level in a group of Turkish patients with rheumatoid arthritis: relationship with disease activity and methotrexate toxicity. Rev Bras Reumatol. 2015. pii: S0482-5004(15)00017-0. doi: 10.1016/j.rbr.2014.12.001.

4. Selhub J. The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr. 2006; 136(6): 1726-1730.

5. Sarwar AB, Sarwar A, Rosen BD, Nasir K. Measuring subclinical atherosclerosis: is homocysteine relevant? Clin Chem Lab Med. 2007; 45(12): 1667-1677.

6. Baskan BM, Sivas F, Aktekin LA, Dogan YP, Ozoran K, Bodur H. Serum homocysteine level in patients with ankylosing spondylitis. Rheumatol Int. 2009; 29(12): 1435-1439.

7. Choi ST, Kim JS, Song JS. Elevated serum homocysteine levels were not correlated with serum uric acid levels, but with decreased renal function in gouty patients. Korean Med Sci. 2014; 29(6): 788-792.

8. Caramaschi P, Martinelli N, Biasi D, Carletto A, Faccini G, Volpe A, et al. Homocysteine plasma concentration is related to severity of lung impairment in scleroderma. J Rheumatol. 2003; 30(2): 298-304.

9. Perna M1, Roman MJ, Alpert DR, Crow MK et al. Relationship of asymmetric dimethylarginine andhomocysteine to vascular aging in systemic lupus erythematosus patients. Arthritis Rheum. 2010; 62(6): 1718-1722.

10. Jednacz E, Rutkowska-Sak L. Atherosclerosis in juvenile idiopathic arthritis. Mediators Inflamm. 2012; 2012: 714732.

11. Slot O. Homocysteine, a marker of cardiovascular disease risk, is markedly elevated in patients with gout. Ann Rheum Dis. 2013; 72(3): 457.

12. Aletaha D, Neogi T, SIlman A, Funovits J, Felson DT et al. 2010 rheumatoid arthritis classification criteria: an America college of rhuematology/European League against Rheumatism collaborative initiative. Ann Rheum Dis. 2010; 69: 1580–1588.

13. Prevoo ML, van’t Hof MA, Kuper HH et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995; 38: 44–48.

14. Van Ede AE, Laan RF, Blom HJ et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatology. 2002; 41(6): 658-665.

15. Kayacelebi AA, Willers J, Pham VV et al. Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease. Amino Acids. 2015 Jan 25. [Epub ahead of print].

16. Willers J, Hahn A. Cardiovascular risk in patients with risk parameters and a German risk score model. Rheumatol Int. 2012; 32(12): 3741-3749.

17. Rezuş E, Floria M, Grigoriu A, Tamba BI, Rezus C. Cardiovascular Risk Factors In Chronic Inflammatory Rheumatic Diseases: Modern Assessment And Diagnosis. Curr Vasc Pharmacol. 2015 Jan 4. [Epub ahead of print].

18. Szekanecz Z, Kerekes G, Der H, Sandor Z et al. Accelerated atherosclerosis in rheumatoid arthritis. Ann N Y Acad Sci. 2007; 1108: 349-358. 19. Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. Arthritis and Rheumatism. 2005; 52(8): 2293–2299.

20. Gonzalez-Gay MA, Gonzalez-Juanatey C, Pineiro A, Garcia-Porrua C, Testa A, Llorca J. High-grade Creactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatology. 2005; 32(7): 1219–1223.

21. Gonzalez-Gay MA, Gonzalez-Juanatey C, Lopez-Diaz MJ, et al. HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum. 2007; 57(1): 125-132.

22. Palomino-Morales R, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, et al. A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis. Arthritis Res Ther. 2010; 12(2): R71.

23. Nowakowska-Plaza A, Potaczek DP, Gluszko P, Undas A. Antibodies to N-homocysteinylated albumin and haemoglobin in patients with rheumatoid arthritis: a 2014; 43(1): 17-21.

24. Woolf K, Manore MM. Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis. J Am Diet Assoc. 2008; 108(3): 443-453.

25. van Ede AE, Laan RF, Blom HJ, Boers GH et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatology. 2002; 41(6): 658-665.

26. Galiutina OIu, Bychak OV. Relationship of silent myocardial ischiemia with the course of rheumatoid arthritis and hyperhomocysteinemia. Lik Sprava. 2011; (1-2): 48-52.

Serbian Journal of Experimental and Clinical Research

The Journal of Faculty of Medical Sciences, University of Kragujevac

Journal Information

CiteScore 2017: 0.21

SCImago Journal Rank (SJR) 2017: 0.126
Source Normalized Impact per Paper (SNIP) 2017: 0.081


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