N-terminal pro-brain natriuretic peptide levels and diastolic dysfunction in patients with early rheumatoid arthritis before the administration of disease-modifying antirheumatic drugs


Aim. To determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with early rheumatoid arthritis (RA) before the use of disease-modifying antirheumatic drugs (DMARDs); to compare NT-proBNP values with traditional risk factors (TRF), cardiovascular diseases (CVD), inflammatory markers, and left ventricular (LV) diastolic dysfunction (DD). Subjects and methods. The investigation enrolled 74 patients with a valid RA diagnosis (the 2010 ACR/EULAR criteria), 56 (74%) women, median (Me) age, 54 years; disease duration, 7 months; seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) with no history of the use of DMARDs and glucocorticosteroids. Duplex scanning and echographic findings were used to assess TRF for CVD and carotid artery atherosclerosis (CAA) in all the patients with early RA prior to therapy. An E/A ratio was used as a criterion for LVDD. Results. NT-proBNP concentrations in patients with early RA proved to be higher than those in the control group (p<0.0001). Higher-than-normal NT-proBNP levels were seen in 36 (49%) patients. The patients with early RA and elevated NT-proBNP values were older and had a higher body mass index (BMI) than those with normal NT-proBNP levels. Those with elevated NT-proBNP concentrations were more frequently found to have CAA, coronary calcification, and coronary heart disease; their intima-media thickness was also larger and C-reactive protein (CRP) levels higher than in those with normal NT-proBNP values. There were correlations between NT-proBNP levels and erythrocyte sedimentation rate, CRP, simplified disease activity index, and clinical disease activity index. Multivariate analysis revealed that chronic heart failure (CHF), CAA, CRP and low-density lipoprotein (LDL) levels, and BMI correlated with NT-proBNP concentrations. LVDD was detected in 35 (48%) patients with early RA. The level of NT-proBNP in patients with DD was higher than in those without DD. Higher-than-normal NT-proBNP values were observed in 23 (65%) and 12 (32%) patients with and without LVDD, respectively. The optimal NT-proBNP level for CHF detection was equal to 237.4 pg/ml (86% sensitivity and 85% specificity); the area under the ROC curve was 0.879. Conclusion. Just at the early disease stage, the patients are noted to have a high NT-proBNP level that is influenced by higher BMI, low LDL levels, CAA, CHF, and high CRP values. In the patients with early RA, the diagnostically significant NT-proBNP concentration for CHF detection was higher (237 pg/ml) than in those without RA (125 pg/ml). The patients with early RA should undergo NT-proBNP determination, LVDD screening, correction of TRF for CVD, atherosclerosis treatment, and remission achievement.


  1. Avina-Zubieta J, Choi H, Sadatsafavi M et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690-1697. doi: 10.1002/art.24092.
  2. Maradit-Kremers H, Nicola PJ, Crowson CS et al. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005;52:722-772. doi: 10.1002/art.24092.
  3. Davis JM 3rd, Roger VL, Crowson CS et al. The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population. Arthritis Rheum. 2008;58:2603-2611. doi: 10.1002/art.24092.
  4. Кириллова И.Г., Новикова Д.С., Попкова Т.В. и др. Диастолическая дисфункция левого и правого желудочков у больных ранним ревматоидным артритом до назначения базисной противовоспалительной терапии. Терапевтический архив. 2015;37(5):16-23.
  5. Munagala VK, Burnett JC, Redfield MM. The natriuretic peptides in cardiovascular medicine. Curr Probl Cardiol. 2004;29:707-769. doi: 10.1016/j.cpcardiol.2004.07.002.
  6. Di AE, Chowdhury R, Sarwar N et al. B-type natriuretic peptides and cardiovascular risk: systematic review and meta-analysis of 40 prospective studies. Circulation. 2009;120:2177-2187. doi: 10.1161/circulationaha.109.884866.
  7. Maisel AS, Krishnaswamy P, Nowak RM et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161-167. doi: 10.1056/nejmoa020233.
  8. Dinh W, Futh R, Nickl W et al. Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders. Cardiovasc Diabetol. 2009;8:58. doi: 10.1186/1475-2840-8-58.
  9. Provan S, Angel K, Semb A et al. NT-proBNP predicts mortality in patients with rheumatoid arthritis: results from 10-year follow-up of the EURIDISS study. Ann Rheum Dis. 2010;69:1946-1950. doi: 10.1136/ard.2009.127704.
  10. Mirjafari H, Welsh P, Suzanne M et al. N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR). Ann Rheum Dis. 2014;73:684-690. doi: 10.1136/annrheumdis-2012-202848.
  11. Рекомендации по кардиоваскулярной профилактике. Комитет экспертов РКО. Кардиоваскулярная терапия и профилактика. 2011;10(6)Приложение 2.
  12. Lafitte S. Do we need new echocardiographic prognosticators for the management of heart failure patients? J Am Coll Cardiol. 2009;54:625-627. doi: 10.1016/j.jacc.2009.04.058.
  13. Lang RM, Bierig RB., Devereux А et al. Recommendations for chamber quantification. Eur J Echocardiography. 2006;7:79-108. doi: 10.1016/j.euje.2005.12.014.
  14. Lang RM, Bierig RB, Devereux, et al. Recommendations for chamber quantification. J Am Soc Echocardiogr. 2005;18:1440-1463. doi: 10.1016/j.echo.2005.10.005.
  15. Национальные рекомендации ОССН, РКО И РНМОТ по диагностике и лечению хронической сердечной недостаточности (четвертый пересмотр). Сердечная недостаточность. 2013;81(7):379-472.
  16. Moraes J, Ribeiro A, Saad C et al. NT-proBNP levels may be influenced by inflammation in active ankylosing spondylitis receiving TNF blockers: a pilot study. Clin Rheumatol. 2013;32:879-883. doi: 10.1007/s10067-013-2182-x.
  17. Crowson C, Myasoedova E, Davis J et al. Use of B-Type Natriuretic Peptide as a screening tool for left ventricular diastolic dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease. Arthritis Care Res. 2011;63(5):729-734. doi: 10.1002/acr.20425.
  18. Casserly BP, Sears EH, Gartman EJ. The role of natriuretic peptides in inflammation and immunity. Recent Pat Inflamm Allergy Drug Discov. 2010;4:90-104. doi: 10.2174/187221310791163125.
  19. Shaw SM, Fildes JE, Puchalka CM et al. BNP directly immunoregulates the innate immune system of cardiac transplant recipients in vitro. Transpl Immunol. 2009;20:199-202. doi: 10.1016/j.trim.2008.08.010.
  20. Omland T, Hagve TA. Natriuretic peptides: physiologic and analytic considerations. Heart Fail Clin. 2009;5:471-487. doi: 10.1016/j.hfc.2009.04.05.
  21. Paganelli R, Di Iorio A, Cherubini A et al. Frailty of older age: the role of the endocrineimmune interaction. Curr Pharm Des. 2006;12:3147-3159. doi: 10.2174/138161206777947533.
  22. Redfield MM, Rodeheffer RJ, Jacobsen SJ et al. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol. 2002;40:976-982. doi: 10.1016/s0735-1097(02)02059-4.
  23. Crowson CS, Liang KP, Therneau TM et al. Could accelerated aging explain the excess mortality in patients with seropositive rheumatoid arthritis? Arthritis Rheum. 2010;62:378-382. doi: 10.1002/art.27194.
  24. Ajeganova S, Andersson ML, Hafstrom I. Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: A long-term followup from disease onset. Arthr Care Res. 2013;65:78-87. doi: 10.1002/acr.21710.
  25. Kenchaiah S, Evans JC, Levy D et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305-313. doi: 10.1056/nejmoa020245.
  26. Slack JD, Waller B. Acute congestive-heart-failure due to the artritis of rheumatoid-arthritis: Early diagnosis by endomyocardial biopsy — a case-report. Angiology. 1986;37:477-482. doi: 10.1177/000331978603700609.
  27. Vasan RS, Benjamin EJ, Larson MG et al. Plasma natriuretic peptides for community screening for left ventricular hypertrophy and systolic dysfunction: The Framingham heart study. J Am Med Assoc. 2002;288:1252-1259. doi: 10.1001/jama.288.10.1252.
  28. Targońska-Stępniak B, Majdan M. Amino-terminal pro-brain natriuretic peptide as a prognostic marker in patients with rheumatoid arthritis. Clin Rheumatol. 2011;30:61-69. doi: 10.1007/s10067-010-1622-0.
  29. Lorgis L, Zeller M, Dentan G et al. High levels of N-terminal pro B- type natriuretic peptide is associated with ST resolution failure after reperfusion for acute myocardial infarction. An Int J Med. 2007;100(4):211-216. doi: 10.1093/qjmed/hcm013.
  30. Bold A, Bold М. Determinants of natriuretic peptide production by the heart: basic and clinical implications. J Invest Med. 2005;53(7):371-377. doi: 10.2310/6650.2005.53710.
  31. Sahinarslan A, Güz G, Mutluay R et al. The impact of dialysis type on biomarkers for cardiovascular diseases. Turk Kardiyol Dern Ars. 2011;39:6:456-462. doi: 10.5543/tkda.2011.01289.
  32. Барбараш О.Л., Усольцева Е.Н., Шафранская К.С. Возможность использования N-терминального фрагмента мозгового натрийуретического пропептида как маркера мультифокального атеросклероза у больных инфарктом миокарда с подъемом сегмента ST. Российский кардиологический журнал. 2012;3:12-18.
  33. Felker GM, Petersen JW, Mark DB. Natriuretic peptides in the diagnosis and management of heart failure. CMAJ. 2006;175:611-617. doi: 10.1503/cmaj.060236.
  34. Maradit-Kremers H, Nicola PJ, Crowson CS et al. Raised erythrocyte sedimentation rate signals heart failure in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66:76-80. doi: 10.1136/ard.2006.053710.
  35. Kumar A, Thota V, Dee L et al. Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med. 1996;3:949-958. doi: 10.1016/s0300-9572(96)90072-6.
  36. Peters MJ, Welsh P, McInnes IB et al. TNF- blockade therapy reduces circulating NT-proBNP levels in RA patients with active disease: results from prospective cohort study. Ann Rheum Dis. 2009;69:1281-1285. doi: 10.1136/ard.2009.119412.
  37. Myasoedova E, Crowson CS, Kremers HM et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011;70(3):482-487. doi: 10.1136/ard.2010.135871.
  38. Giannoni A, Tani C, Clerico A et al. When the heart is burning: amino-terminal pro-brain natriuretic peptide as an early marker of cardiac involvement in active autoimmune rheumatic disease. Int J Cardiol. 2009;148(2):161-167. doi: 10.1016/j.ijcard.2009.10.048.
  39. Solus J, Chung CP, Oeser A et al. Amino-terminal fragment of the prohormone brain- B-Type natriuretic peptide in rheumatoid arthritis. Arthritis Rheum. 2008;58:2662-2669. doi: 10.1002/art.23796.
  40. Nicola PJ, Maradit-Kremers H, Roger VL et al. The risk of congestive heart failure in rheumatoid arthritis. Arthritis Rheum. 2005;2:412-420. doi: 10.1002/art.20855.
  41. Al-Barjas M, Nair D, Morris R et al. How can the role of N terminal pro B Natriuretic Peptide (NT-proBNP) be optimized in heart failure screening? A prospective observation comparative study. Eur J Heart Fail. 2004;3:51 Suppl 1. doi: 10.1016/s1567-4215(04)90150-6.
  42. Lubien E, DeMaria A, Krishnaswamy P, Clopton P, Koon J, Kazanegra R, Gardetto N, Wanner E, Maisel AS. Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings. Circulation. 2002;105:595-601. doi: 10.1161/hc0502.103010.



Abstract - 95

PDF (Russian) - 15


Article Metrics

Metrics Loading ...


  • There are currently no refbacks.

Copyright (c) 2020 Kirillova I.G., Novikova D.S., Popkova T.V., Aleksandrova E.N., Novikov A.A., Gorbunova Y.N., Markelova E.I., Korsakova Y.O., Glukhova S.I., Volkov A.V., Luchikhina E.L., Demidova N.V., Kasumova K.A., Vladimirov S.A., Kanonirova M.A., Lukina G.L., Karateev D.E., Nasonov E.L.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Novoslobodskaya str 31c4., Moscow, 127005, Russian Federation

Managing Editor:


© 2018 "Consilium Medicum" Publishing house

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies