European Heart Journal Advance Access originally published online on December 12, 2006
European Heart Journal 2007 28(1):140-141; doi:10.1093/eurheartj/ehl425
N-terminal brain natriuretic peptide in scleroderma-associated pulmonary arterial hypertension
Pulmonary and Critical Care Medicine
Johns Hopkins University
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E-mail address: smathai4{at}jhmi.edu
Pulmonary and Critical Care Medicine
Johns Hopkins University
1830 East Monument Street
Baltimore
Maryland 21205
USA
We read with great interest the report by Williams et al.1 regarding N-TproBNP levels in patients with scleroderma-associated pulmonary arterial hypertension (SSc-PAH). In studying a large cohort of scleroderma patients, the authors found that N-TproBNP levels (i) significantly correlate with cardiopulmonary haemodynamics, (ii) predict development of pulmonary hypertension in patients with scleroderma, and (iii) predict survival. These findings are quite important given the need for reliable non-invasive tools to assess pulmonary hypertension. However, several issues regarding the study may limit the inferences that can be drawn.
First, as the authors acknowledge, since the majority of patients with SSc-PAH were already on therapy, the ability of N-TproBNP >395 pg/mL to discriminate between those with and without PAH is questionable, as the effect of therapy upon N-TproBNP levels is not known. Further, although the cutoff value of 395 pg/mL was derived from a prior study,2 this value was not adjusted for age and gender, which have been shown to influence absolute levels of measured natriuretic peptides.3 Additionally, recent evidence suggests that an inverse relationship between obesity and N-TproBNP exists.4 No adjustment for body mass index was performed.
Co-morbidities such as coronary artery disease may affect N-TproBNP levels.5 There appears to be differential assessment of the cases and controls as only the controls were required to undergo left heart catheterization to evaluate any possible coronary disease. Since elevation of BNP levels may occur in pre-clinical coronary heart disease not seen on echocardiography,6 the difference in N-TproBNP levels between cases and controls may be exaggerated by concomitant elevations due to undetected coronary disease.
Finally, the analysis was not controlled for patients with interstitial lung disease associated with scleroderma (SSc-ILD). Although ‘significant’ ILD was an exclusion criterion for the study, a higher proportion of patients with evidence of SSc-ILD were included in the SSc-PAH group. It is unknown whether ILD may influence N-TproBNP levels independent of pulmonary hypertension. Further, the higher proportion of patients in the PAH group with ILD may bias the survival analysis. Our experience shows that patients with pulmonary hypertension related to SSc-ILD have much worse survival compared with those with PAH related to scleroderma.7
References
- Williams MH, Handler CE, Akram R, Smith CJ, Das C, Smee J, Nair D, Denton CP, Black CM, Coghlan JG. (2006) Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. Eur Heart J 27:1485–1494.
[Abstract/Free Full Text] - Mukerjee D, Yap LB, Holmes AM, Nair D, Ayrton P, Black CM, Coghlan JG. (2003) Significance of plasma N-terminal pro-brain natriuretic peptide in patients with systemic sclerosis-related pulmonary arterial hypertension. Respir Med 97:1230–1236.[CrossRef][Web of Science][Medline]
- Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. (2002) Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 40:976–982.
[Abstract/Free Full Text] - Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH Jr, de Lemos JA. (2005) Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation 112:2163–2168.
- Goetze JP, Christoffersen C, Perko M, Arendrup H, Rehfeld JF, Kastrup J, Nielsen LB. (2003) Increased cardiac BNP expression associated with myocardial ischemia. FASEB J 17:1105–1107.
[Abstract/Free Full Text] - McKie PM and Burnett JC Jr. (2005) B-type natriuretic peptide as a biomarker beyond heart failure: speculations and opportunities. Mayo Clin Proc 80:1029–1036.
[Abstract/Free Full Text] - Girgis RE, Mathai SC, Champion HC, Hummers L, Wigley FM, Hassoun PM. (2006) Determinants of survival in pulmonary hypertension associated with scleroderma. J Heart Lung Transplant 25:S77.
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