Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate

ÇINAR, Ziynet; HAYTA, Emrullah; HİZMETLİ, Sami; ATALAR, Mehmet Haydar

Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate

Emrullah HAYTA, (Cumhuriyet Üniversitesi, Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, Sivas, Türkiye)

Sami HİZMETLİ, (Cumhuriyet Üniversitesi, Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, Sivas, Türkiye)

Mehmet Haydar ATALAR, (Cumhuriyet Üniversitesi, Tıp Fakültesi, Radyoloji Anabilim Dalı, Sivas, Türkiye)

Ziynet ÇINAR (Cumhuriyet Üniversitesi, Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Sivas, Türkiye)

Archives of Rheumatology

6 0

Yıl: 2015 Cilt: 30 Sayı: 3 Sayfa Aralığı: 214 - 220 Metin Dili: İngilizce İndeks Tarihi: 29-07-2022

Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate

Öz:

Objectives: This study aims to evaluate the relationship between serum homocysteine levels and atherosclerotic plaques in carotid arteries in female patients with rheumatoid arthritis (RA). Patients and methods: Fifty-eight females with RA (mean age 45.50±11.69 years; range 42 to 60 years) and 22 female controls (mean age 47.3±8.9 years; range 38 to 62 years) with mechanical low back pain were included in the study. RA patients were divided into two groups: patients who were under methotrexate (MTX) therapy at least for two years (MTX group, n=32), and patients who did not receive MTX at least for past two years (nonMTX-disease-modifying antirheumatic drug group, n=26). RA patients disease activity scores in 28 joints were calculated. Carotid intima-media thickness and presence of atherosclerotic plaque were evaluated by high-resolution B-mode ultrasonography. Results: Plasma homocysteine levels were higher in MTX and non-MTX-disease-modifying antirheumatic drug groups compared to controls (16.88±6.84 and 10.37±2.54 μmol/L, respectively) and the difference was statistically significant (p=0.001). In MTX, non-MTX-disease-modifying antirheumatic drug and control groups, atherosclerotic plaque was detected in 11 (34.5%) and four (15.4%) patients, and one patient (4.5%), respectively. Carotid intima-media thickness was significantly higher in MTX group compared to other two groups and the difference was statistically significant (p=0.002). Pearson correlation analysis revealed a significant correlation between intima-media thickness and homocysteine levels in MTX group (r=0.49, p=0.006). Conclusion: According to our study results, methotrexate treatment in female patients with RA increases plasma homocysteine levels and prevalence of atherosclerotic plaque. High homocysteine levels in these patients may be a cause of atherosclerosis.

Anahtar Kelime:

Konular: Romatoloji

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Maini RN, Zvaifler NJ. Rheumatoid arthritis and spondyloarthropathy. In: Klippel JH, Dieppe PA, editors. Rheumatology. St Louis: Mosby; 1994. p. 3:1,1-40:1.
2. Kerekes G, Szekanecz Z, Dér H, Sándor Z, Lakos G, Muszbek L, et al. Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity. J Rheumatol 2008;35:398-406.
3. Kapetanovic MC, Lindqvist E, Simonsson M, Geborek P, Saxne T, Eberhardt K. Prevalence and predictive factors of comorbidity in rheumatoid arthritis patients monitored prospectively from disease onset up to 20 years: lack of association between inflammation and cardiovascular disease. Scand J Rheumatol 2010;39:353-9.
4. Ciftci O, Yilmaz S, Topcu S, Caliskan M, Gullu H, Erdogan D, et al. Impaired coronary microvascular function and increased intima-media thickness in rheumatoid arthritis. Atherosclerosis 2008;198:332-7.
5. del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001;44:2737-45.
6. van Ede AE, Laan RF, Blom HJ, Boers GH, Haagsma CJ, Thomas CM, et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatology (Oxford) 2002;41:658-65.
7. Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis 2011;34:75-81.
8. Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate. Clin Chem 2000;46:1277-83.
9. Ferretti G, Bacchetti T, Moroni C, Vignini A, Nanetti L, Curatola G. Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells. J Cell Biochem 2004;92:351-60.
10. Wållberg-Jonsson S, Ohman M, Rantapää-Dahlqvist S. Which factors are related to the presence of atherosclerosis in rheumatoid arthritis? Scand J Rheumatol 2004;33:373-9.
11. Jacobsson LT, Knowler WC, Pillemer S, Hanson RL, Pettitt DJ, McCance DR, et al. A cross-sectional and longitudinal comparison of the Rome criteria for active rheumatoid arthritis (equivalent to the American College of Rheumatology 1958 criteria) and the American College of Rheumatology 1987 criteria for rheumatoid arthritis. Arthritis Rheum 1994;37:1479-86.
12. Kang SS, Wong PW, Malinow MR. Hyperhomocyst(e) inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr 1992;12:279-98.
13. Jadhav UM, Kadam NN. Apolipoproteins: correlation with carotid intimamedia thickness and coronary artery disease. J Assoc Physicians India 2004;52:370-5.
14. Mitu F, Mitu M, Turiceanu M, Caliap TA, Leatu CG. The importance of carotid ultrasound in the risk stratification of patients with ischaemic heart disease. Rev Med Chir Soc Med Nat Iasi 2008;112:337-42. [Abstract]
15. Rosvall M, Janzon L, Berglund G, Engström G, Hedblad B. Incidence of stroke is related to carotid IMT even in the absence of plaque. Atherosclerosis 2005;179:325-31.
16. Polak JF, Backlund JY, Cleary PA, Harrington AP, OLeary DH, Lachin JM, et al. Progression of carotid artery intima-media thickness during 12 years in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Diabetes 2011;60:607-13.
17. Kim HS, Cho KI. Association of carotid artery parameters of atherosclerosis in coronary artery disease. J Cardiovasc Ultrasound 2013;21:72-80.
18. Gómez-Vaquero C, Corrales A, Zacarías A, Rueda-Gotor J, Blanco R, González-Juanatey C, et al. SCORE and REGICOR function charts underestimate the cardiovascular risk in Spanish patients with rheumatoid arthritis. Arthritis Res Ther 2013;15:91.
19. Gonzalez A, Maradit Kremers H, Crowson CS, Ballman KV, Roger VL, Jacobsen SJ, et al. Do cardiovascular risk factors confer the same risk for cardiovascular outcomes in rheumatoid arthritis patients as in non-rheumatoid arthritis patients? Ann Rheum Dis 2008;67:64-9.
20. González-Gay MA, González-Juanatey C. Implication of new atherosclerotic carotid plaques in the cardiovascular outcome of patients with rheumatoid arthritis. Arthritis Res Ther 2012;14:105.
21. Gkaliagkousi E, Gavriilaki E, Doumas M, Petidis K, Aslanidis S, Stella D. Cardiovascular risk in rheumatoid arthritis: pathogenesis, diagnosis, and management. J Clin Rheumatol 2012;18:422-30.
22. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325:1202.
23. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a metaanalysis. JAMA 2002;288:2015-22.
24. Cleophas TJ, Hornstra N, van Hoogstraten B, van der Meulen J. Homocysteine, a risk factor for coronary artery disease or not? A meta-analysis. Am J Cardiol 2000;86:1005-9.
25. Roubenoff R, Dellaripa P, Nadeau MR, Abad LW, Muldoon BA, Selhub J, et al. Abnormal homocysteine metabolism in rheumatoid arthritis. Arthritis Rheum 1997;40:718-22.
26. Cisternas M, Gutiérrez MA, Klaassen J, Acosta AM, Jacobelli S. Cardiovascular risk factors in Chilean patients with rheumatoid arthritis. J Rheumatol 2002;29:1619-22.
27. Lopez-Olivo MA, Gonzalez-Lopez L, GarciaGonzalez A, Villa-Manzano AI, Cota-Sanchez AR, Salazar-Paramo M, et al. Factors associated with hyperhomocysteinaemia in Mexican patients with rheumatoid arthritis. Scand J Rheumatol 2006;35:112-6.
28. Hoekstra M, Haagsma CJ, Doelman CJ, van de Laar MA. Intermittent rises in plasma homocysteine in patients with rheumatoid arthritis treated with higher dose methotrexate. Ann Rheum Dis 2005;64:141-3.
29. Morgan SL, Baggott JE, Lee JY, Alarcón GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998;25:441-6.
30. Yang HT, Lee M, Hong KS, Ovbiagele B, Saver JL. Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials. Eur J Intern Med 2012;23:745-54.
31. Haagsma CJ, Blom HJ, van Riel PL, vant Hof MA, Giesendorf BA, van Oppenraaij-Emmerzaal D, et al. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis 1999;58:79-84.
32. Hernanz A, Plaza A, Martín-Mola E, De Miguel E. Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women. Clin Biochem 1999;32:65-70.
33. Cuomo G, Di Micco P, Niglio A, La Montagna G, Valentini G. Atherosclerosis and rheumatoid arthritis: relationships between intima-media thickness of the common carotid arteries and disease activity and disability. Reumatismo 2004;56:242-6. [Abstract]
34. Nagata-Sakurai M, Inaba M, Goto H, Kumeda Y, Furumitsu Y, Inui K, et al. Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis. Arthritis Rheum 2003;48:3061-7.

APA	HAYTA E, HİZMETLİ S, ATALAR M, ÇINAR Z (2015). Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. , 214 - 220.
Chicago	HAYTA Emrullah,HİZMETLİ Sami,ATALAR Mehmet Haydar,ÇINAR Ziynet Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. (2015): 214 - 220.
MLA	HAYTA Emrullah,HİZMETLİ Sami,ATALAR Mehmet Haydar,ÇINAR Ziynet Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. , 2015, ss.214 - 220.
AMA	HAYTA E,HİZMETLİ S,ATALAR M,ÇINAR Z Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. . 2015; 214 - 220.
Vancouver	HAYTA E,HİZMETLİ S,ATALAR M,ÇINAR Z Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. . 2015; 214 - 220.
IEEE	HAYTA E,HİZMETLİ S,ATALAR M,ÇINAR Z "Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate." , ss.214 - 220, 2015.
ISNAD	HAYTA, Emrullah vd. "Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate". (2015), 214-220.

APA	HAYTA E, HİZMETLİ S, ATALAR M, ÇINAR Z (2015). Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. Archives of Rheumatology, 30(3), 214 - 220.
Chicago	HAYTA Emrullah,HİZMETLİ Sami,ATALAR Mehmet Haydar,ÇINAR Ziynet Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. Archives of Rheumatology 30, no.3 (2015): 214 - 220.
MLA	HAYTA Emrullah,HİZMETLİ Sami,ATALAR Mehmet Haydar,ÇINAR Ziynet Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. Archives of Rheumatology, vol.30, no.3, 2015, ss.214 - 220.
AMA	HAYTA E,HİZMETLİ S,ATALAR M,ÇINAR Z Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. Archives of Rheumatology. 2015; 30(3): 214 - 220.
Vancouver	HAYTA E,HİZMETLİ S,ATALAR M,ÇINAR Z Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate. Archives of Rheumatology. 2015; 30(3): 214 - 220.
IEEE	HAYTA E,HİZMETLİ S,ATALAR M,ÇINAR Z "Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate." Archives of Rheumatology, 30, ss.214 - 220, 2015.
ISNAD	HAYTA, Emrullah vd. "Association of Plasma Homocysteine Level and Carotid Intima-Media Thickness in Rheumatoid Arthritis Patients Receiving Methotrexate". Archives of Rheumatology 30/3 (2015), 214-220.