Cardiovascular diseases in patients with rheumatoid arthritis during long-term methotrexate therapy


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AIM: To compare the prevalence of risk factors, clinical and subclinical manifestations of cardiovascular diseases (CVD) and their complications in methotrexate (MT)-treated and untreated patients with rheumatoid arthritis/MATERIAL AND METHODS: The investigation enrolled 193 patients (168 women and 25 men) less than 60 years of age (mean age 49 [44; 53] years) with RA. The patients were divided into 2 groups: 1) 69 patients who received MT in a dose of 15.1 [10.2; 21] mg/week for at least 12 months (mean disease duration 25 [18; 48] months); 2) 124 patients who did not take MT. The patient groups were matched for age, gender, disease duration, RA activity, and the rate of rheumatoid factor (RF) seropositivity and extraarticular manifestations/RESULTS: Dyslipidemia was significantly less frequently identified in MT-treated patients (35/69 or 51%) than in MT-untreated ones (85/124 or 69%; p=0.01). The serum from the patients treated with MT exhibited higher high-density lipoprotein cholesterol concentrations ((1.8 [0.9; 2.0] mmol/l) than in those untreated with MT (1.2 [1.0; 1.6] mmol/l; р=0,047). In Group 1, hypertension (49%) and diabetes mellitus (3%) were slightly rare than in Group 2 (62 and 13%, respectively; p>0.05). Carotid atherosclerotic plaques were found in 19 and 16% and intima-media thickness (IMT) enlargement was seen in 53 and 56% of the patients in Groups 1 and 2, respectively. Silent myocardial ischemia was diagnosed in every 10 patients; heart disease (exertional angina, myocardial infarction) was in every 5 patients in both groups. Aortocoronary bypass surgery was performed in 2 (3%) patients from those who received MT and had experienced MI and in one (1.6%) patient from the MT-untreated group/CONCLUSION: Long-term MT therapy was associated with the lower rate of dyslipidemia, but it failed to affect the incidence of CVD in patients with RA.

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Сердечно-сосудистые заболевания у больных ревматоидным артритом на фоне длительной терапии метотрексатом. - Резюме. Цель исследования. Сопоставить распространенность факторов риска, клинических и субклинических проявлений сердечно-сосудистых заболеваний (CCЗ) и их осложнений у больных ревматоидным артритом (РА), получавших терапию метотрексатом (МТ) и без таковой. Материалы и методы. В исследование включили 193 пациентов с РА (168 женщин и 25 мужчин) моложе 60 лет (средний возраст 49 [44; 53] лет). Пациенты были разделены на 2 группы: 1-я включала 69 больных, получавших МТ не менее 12 мес (средняя длительность терапии 25 [18; 48] мес) в дозе 15,1 [10, 2; 21] мг/нед, 2-я группа - 124 пациента без терапии МТ. Группы больных были сопоставимы по возрасту, полу, продолжительности заболевания, активности РА, частоте серопозитивности по ревматоидному фактору (РФ) и внесуставных проявлений. Результаты. Дислипидемия достоверно реже выявлялась у больных, получавших терапию МТ (35/69, или 51%), по сравнению с пациентами без таковой (85/124, или 69%; р=0,01). В сыворотке больных, получавших МТ, обнаружена более высокая концентрация холестерина липопротеидов высокой плотности (1,8 [0, 9; 2, 0] ммоль/л) по сравнению с группой пациентов, не получавших МТ (1,2 [1, 0; 1, 6] ммоль/л; р=0,047). В 1-й группе больных артериальная гипертония (49%) и сахарный диабет (3%) встречались несколько реже, чем у пациентов 2-й группы (62 и 13% соответственно; р>0,05). Атеросклеротические бляшки сонных артерии обнаружены у 19 и 16%, увеличение толщины комплекса интима-медиа (ТИМ) - у 53 и 56% больных 1-й и 2-й групп соответственно. Безболевая ишемия миокарда диагностирована у каждого 10-го больного, ишемическая болезнь сердца (стенокардия напряжения, инфаркт миокарда) - у каждого 5-го больного в обеих группах. Аортокоронарное шунтирование выполнено 2 (3%) пациентам получавшим МТ и перенесшим ИМ, и 1 (1,6%) больному без МТ. Заключение. Длительная терапия МТ ассоциировалась с меньшей частотой дислипидемий, но не влияла на частоту развития ССЗ у больных РА.
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References

  1. Ревматология: национальное руководство. Под ред. Е.Л. Насонова, В.А. Насоновой. М: ГЭОТАР-Медиа 2008; 720.
  2. Meune C., Touze E., Trinqurte L., Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology 2009; 48: 1309-1313.
  3. van Halm V.P., Peters M.J., Voskuyl A.E. et al. Rheumatoid arthritis versus type 2 diabetes as a risk factor for cardiovascular disease: a cross-sectional study. Ann Rheum Dis 2009; 68: 1395-1400.
  4. Nielen M.M., van Sijl A.M., Peters M.J. et al. Cardiovascular disease prevalence in patients with inflammatory arthritis, diabetes mellitus and osteoarthritis: a cross-sectional study in primary care. BMC Musculoskelet Disord 2012; 13: 150.
  5. Goodson N.J., Symmons D.P., Scott D.G. et al. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year follow up study of a primary care-based inception cohort. Arthritis Rheum 2005; 52: 2293-2299.
  6. Poole C.D., Conway P., Currie C.J. An evaluation of the association between C-reactive protein, the change in C-reactive protein over one year, and all-cause mortality in chronic immune-mediated inflammatory disease managed in UK general practice. Rheumatology (Oxford) 2009; 48: 78-82.
  7. Jacobsson L.T., Turesson C., Hanson R.L. et al. Joint swelling as a predictor of death from cardiovascular disease in a population study of Pima Indians. Arthritis Rheum 2001; 44: 1170-1176.
  8. Rho Y.H., Chung C.P., Oeser A. et al. Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum 2009; 61 (11): 1580-1585.
  9. Goodson N.J., Wiles N.J., Lunt M. et al. Mortality on early inflammatory arthritis: cardiovascular mortality in seropositive patients. Arthritis Rheum 2002; 46: 2010-2019.
  10. López-Longo F.J., Oliver-Mi?arro D., de la Torre I. et al. Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Rheum 2009; 61: 419-424.
  11. Попкова Т.В., Новикова Д.С., Насонов Е.Л. Атеросклероз при ревматических заболеваниях. В кн.: Ревматология: клинические рекомендации. M: ГЭОТАР-Медиа 2010: 678-702.
  12. Choi H.K., Hern?n M.A., Seeger J.D. et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359 (9313): 1173-1177.
  13. Mikuls T.R., Fay B.T., Michaud K. et al. Associations of disease activity and treatments with mortality in men with rheumatoid arthritis: results from the VARA registry. Rheumatology (Oxford) 2011; 50 (1): 101-109.
  14. vanHalm V.P., Nurmohamed M.T., Twisk J.W. Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. Arthritis Res Ther 2006; 8 (5): R151.
  15. Hochberg M.C., Johnston S.S., John A.K. The incidence and prevalence of extra-articular and systemic manifestations in a cohort of newly-diagnosed patients with rheumatoid arthritis between 1999 and 2006. Curr Med Res Opin 2008; 24 (2): 469-480.
  16. Naranjo A., Sokka T., Descalzo M.A. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res Ther 2008; 10 (2): R30.
  17. Goodson N.J. The mortality association with DMARD usein early inflammatory polyarthritis. Rheumatology 2008; 47: 49.
  18. Greenberg J.D., Kremer J.M., Curtis J.R. Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann Rheum Dis 2011; 70: 576-582.
  19. Radovits B.J., Popa-Diaconu D.A., Popa C. Disease activity as a risk factor for myocardial infarction in rheumatoid arthritis. Ann Rheum Dis 2009; 68 (8): 1271-1276.
  20. Suissa S., Bernatsky S., Hudson M. Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum 2006; 55 (4): 531-536.
  21. Edwards C.J. Myocardial infarction in rheumatoid arthritis. The effects of DMARDs and prednisolone. Arthritis Rheum 2008; 56: 668.
  22. Micha R., Imamura F., Wyler von Ballmoos M. et al. Systemic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 2011; 108 (9): 1362-1370.
  23. Westlake S.L., Colebatch A.N., Baird J. et al. The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systemic literature review. Rheumatology 2010; 49: 295-307.
  24. Reiss A.B., Carsons S.E., Anwar K. et al. Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum 2008; 58 (12): 3675-3683.
  25. Coomes E., Chan E.S.L., Reiss A.B. Methotrexate in atherogenesis and cholesterol metabolism. Cholesterol 2011; 2011: 503028.
  26. Chen D.Y., Chih H.M., Lan J.L. et al. Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment. BMC Med 2011; 9: 4.
  27. Toms T.E., Panoulas V.F., John H. et al. Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study. Arthritis Res Ther 2009; 11 (4): R110.
  28. Barzi F., Patel A., Woodward M. et al. Asia Pacific Cohort Studies Collaboration. A comparison of lipid variables as predictors of cardiovascular disease in the Asia Pacific region. Ann Epidemiol 2005; 15 (5): 405-413.
  29. Bittner V., Johnson B.D., Zineh I. et al. The triglyceride/high-density lipoprotein cholesterol ratio predicts all-cause mortality in women with suspected myocardial ischemia: a report from the Women's Ischemia Syndrome Evaluation (WISE). Am Heart J 2009; 157 (3): 548-555.
  30. Georgiadis A.N., Papavasiliou E.C., Lourida E.S. et al. Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment--a prospective, controlled study. Arthritis Res Ther 2006; 8 (3): R82.
  31. Park Y.B., Choi H.K., Kim M.Y. et al. Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: a prospective study. Am J Med 2002; 113 (3): 188-193.
  32. Dessein P.H., Joffe B.I., Stanwix A.E. Effects of disease modifying agents and dietary intervention on insulin resistance and dyslipidemia in inflammatory arthritis: a pilot study. Arthritis Res 2002; 4 (6): R12.
  33. Chen D.Y., Chih H.M., Lan J.L. et al. Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment. BMC Med 2011; 9: 4.
  34. Panoulas V.F., Douglas K.M., Milionis H.J. et al. Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis. Rheumatology (Oxford) 2007; 46 (9): 1477-1482.
  35. Raterman H.G., Voskuyl A.E., Dijkmans B.A., Nurmohamed M.T. Use of methotrexate therapy is not associated with decreased prevalence of metabolic syndrome. Arthritis Res Ther 2009; 11 (5): 413; author reply 414.
  36. Joost H.G., Weber T.M., Cushman S.W., Simpson I.A. Insulin-stimulated glucose transport in rat adipose cells. Modulation of transporter intrinsic activity by isoproterenol and adenosine. J Biol Chem 1986; 261 (22): 10033-10036.
  37. Hajer G.R., van der Graaf Y., Olijhoek J.K. et al. SMART Study Group. Levels of homocysteine are increased in metabolic syndrome patients but are not associated with an increased cardiovascular risk, in contrast to patients without the metabolic syndrome. Heart 2007; 93 (2): 216-220.
  38. Bulgarelli A., Martins Dias A.A., Caramelli B., Maranhão R.C. Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits. J Cardiovasc Pharmacol 2012; 59 (4): 308-314.
  39. Marks J.L., Edwards C.J. Protective effect of methotrexate in patients with rheumatoid arthritis and cardiovascular comorbidity. Ther Adv Musculoskelet Dis 2012; 4 (3): 149-157.
  40. Ristić G.G., Lepić T., Glisić B. et al. Rheumatoid arthritis is an independent risk factor for increased carotid intima-media thickness: impact of anti-inflammatory treatment. Rheumatology (Oxford). 2010; 49 (6): 1076-1081.
  41. Georgiadis A.N., Voulgari P.V., Argyropoulou M.I. et al. Early treatment reduces the cardiovascular risk factors in newly diagnosed rheumatoid arthritis patients. Semin Arthritis Rheum 2008; 38 (1): 13-19.
  42. Turiel M., Tomasoni L., Sitia S. et al. Effects of long-term disease-modifying antirheumatic drugs on endothelial function in patients with early rheumatoid arthritis. Cardiovasc Ther 2010; 28 (5): e53-64.
  43. Wallberg-Jonsson S., Ohman M. and Rantapaa Dahlqvist S. Which factors are related to the presence of atherosclerosis in rheumatoid arthritis? Scand J Rheumatol 2004; 33: 373-379.
  44. Kumeda Y., Inaba M., Goto H. et al. Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum 2002; 46 (6): 1489-1497.
  45. Новикова Д.С., Попкова Т.В., Герасимов А.Н. и др. Взаимосвязь кардиоваскулярных факторов риска с ригидностью артериальной стенки у женщин с высокой активностью ревматоидного артрита. Рацион фармакотер в кардиол 2012; 6: 756-765.
  46. Endean A. The risk of stroke in patients with rheumatoid arthritis compared to the general population. Arhritis Rheum 2007; 56: S293.

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