The Reasons of Higher NT-proBNP Depend On Very Different Conditions

Mehmet Aydogan, MD,

Other Contributors:

April 12, 2013

Dear Editor,

We read the article ''N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis (IP): results from the Norfolk Arthritis Registry (NOAR).'' by Mirjafari et al with interest(1). The authors aimed to measure serum NT-pro-BNP levels in a large, well characterised inception cohort of patients with early IP and to examine baseline association of NT-pro-BNP levels with IP disease phenotype, clinical cardiovascular diseases (CVD) risk markers and subclinical atherosclerosis surrogates. They concluded that in early IP patients, elevated NT-pro-BNP is related to Health Assessment Questionnaire (HAQ) and CRP and predicts all-cause and CVD mortality independently of conventional CVD risk factors.

The neurohormone B-type natriuretic peptide (BNP) is a regulator of cardiovascular function. BNP is produced primarily in the ventricular myocardium. and production of them is controlled by stretch receptors. The precursor protein pro-B-type natriuretic peptide is reserve to form BNP and the amino terminal N-terminal pro-B-type natriuretic peptide (NT- proBNP), both of which circulate in the plasma (2,3). Although most widely used as a marker of systolic heart failure, elevated natriuretic peptide levels (NPs) have been reported in patients with diastolic dysfunction (4). Therefore, it's important to determine diastolic and systolic function by echocardiography. Performing of echocardiography is also important for measurement of pulmonary artery pressure. Because pulmonary arterial hypertension (PAH) is common with rheumatic diseases and high NP levels may be a result of the increase in pulmonary pressure (5-7). On the other hand, high levels of NPs can be seen in many cases which increase cardiac output and cardiac stress such as sepsis, cirrhosis, hyperthyroidism, renal failure(8-10). Reduction of renal clearance of NPs may be another reason of elevated NPs in renal failure. That's why, determination of liver and renal function tests, thyroid hormones profile may reveal a stronger results in such a study. Another group of diseases seen in the high levels of NPs is respiratory system diseases. NPs levels are elevated in response to pressure of right heart in respiratory diseases such as COPD, pulmonary embolism, interstitial lung disease (11,12). In addition, cor pulmonale, secondary pulmonary hypertension, or hypoxemia may represent important stimuli for the release of NP from the right heart. In conclusion, elevated NT-pro-BNP predicts all-cause and CVD mortality independently of conventional CVD risk factors and more importantly is related to HAQ and CRP as presented in the current study. However the reasons of higher NT-pro-BNP depend on very different conditions and the pivotal roles of those factors evaluate further large-scale prospective randomized clinical trials.


1. Mirjafari H, Welsh P, Verstappen SM, et al. N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis (IP): results from the Norfolk Arthritis Registry (NOAR). Ann Rheum Dis 2013 Mar 19. [Epub ahead of print].

2. Palazzuoli A, Gallotta M, Quatrini I, et al. Natriuretic peptides (BNP and NT-proBNP): measurement and relevance in heart failure. Vasc Health Risk Manag 2010;6:411-8.

3. Hall C. Essential biochemistry and physiology of (NT-pro)BNP. Eur J Heart Fail 2004;6(3):257-60.

4. Tschöpe C, Kasner M, Westermann D, et al. The role of NT-proBNP in the diagnostics of isolated diastolic dysfunction: correlation with echocardiographic and invasive measurements. Eur Heart J 2005;26(21):2277-84.

5. Andersen CU, Mellemkjaer S, Nielsen-Kudsk JE, et al. Diagnostic and prognostic role of biomarkers for pulmonary hypertension in interstitial lung disease. Respir Med 2012;106(12):1749-55.

6. Tian Z, Guo XX, Li MT, et al. [The value of brain natriuretic peptide in connective tissue diseases associated with pulmonary arterial hypertension]. Zhonghua Nei Ke Za Zhi 2011 ;50(2):102-6.

7. Clements PJ, Tan M, McLaughlin VV, et al. The pulmonary arterial hypertension quality enhancement research initiative: comparison of patients with idiopathic PAH to patients with systemic sclerosis- associated PAH. Ann Rheum Dis 2012;71(2):249-52

8. Bodlaj G, Pichler R, Brandst?tter W, et al. Hyperthyroidism affects arterial stiffness, plasma NT-pro-B-type natriuretic peptide levels, and subendocardial perfusion in patients with Graves' disease. Ann Med 2007;39(8):608-16.

9. Ljubicic N, Gomerci? M, Zekanovi? D, et al. New insight into the role of NT-proBNP in alcoholic liver cirrhosis as a noninvasive marker of esophageal varices. Croat Med J 2012;53(4):374-8.

10. Ookura H, Ito H, Yoshioka H, et al. Study on the diagnostic role of NT -proBNP assay for assessment of cardiac function, and the effect of renal function--comparable study with BNP. Rinsho Byori 2010;58(2):139-47.

11. Marcun R, Sustic A, Brguljan PM, et al. Cardiac biomarkers predict outcome after hospitalisation for an acute exacerbation of chronic obstructive pulmonary disease. Int J Cardiol 2012;161(3):156-9.

12. Winkler BE, Schuetz W, Froeba G, et al. N-terminal prohormone of brain natriuretic peptide: a useful tool for the detection of acute pulmonary artery embolism in post-surgical patients. Br J Anaesth 2012;109(6):907-10.

Conflict of Interest:

None declared

Conflict of Interest

None declared