European Heart Journal Advance Access originally published online on January 23, 2006
European Heart Journal 2006 27(5):622-623; doi:10.1093/eurheartj/ehi739
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Normal range of N-terminal pro-brain natriuretic peptide: a note of caution: reply
Department of Cardiovacular Medicine
Northwick Park Hospital
Harrow
Middlesex HA1 3UJ
UK
Department of Cardiovacular Medicine
Northwick Park Hospital
Harrow
Middlesex HA1 3UJ
UK
E-mail address: roxy.senior{at}virgin.net
We would like to answer to Wolber and Maeder's comments in turn.
They state that our conclusions must be taken with caution, as silent coronary artery disease (CAD) was not ruled out. There is, however, no evidence that screening for silent CAD even by coronary angiography produces prognostic benefit, so we were entitled not to assess this, sticking to conditions where early screening may be beneficial. Moreover, our conclusions stated that normal NTpBNP levels ruled out many significant cardiovascular conditions, not cardiovascular disease in general as they suggest.
They are similarly concerned that the developed NTpBNP upper reference values may be too high as subjects with silent CAD could have been included in the normal group, recommending diagnostic angiography in these subjects. Certainly, we tried to make this group as normal as possible, excluding those with known cardiovascular risk factors or disease or those found to have hypertension, renal dysfunction, or echocardiographic abnormalities. This we feel would leave very few, if any, subjects with important silent CAD. Furthermore, whether such subjects, if present, would have had raised NTpBNP levels is unclear, with no prior study analysing NTpBNP levels in subjects with asymptomatic CAD. Indeed, the paper by Kragelund et al.1 from which they quote found that in subjects with symptoms or signs of CAD, NTpBNP levels were raised the most in those with left ventricular systolic dysfunction, prior heart attack, diabetes mellitus, clinically significant CAD and renal dysfunction, conditions all excluded in our normal range assessment, and increased age, something stratified for in our study. Furthermore, there was virtually no difference in NTpBNP levels between those with or without CAD on angiography if left ventricular ejection fraction was normal, despite a higher risk profile in those with CAD. Thus, the merits and indeed the ethics of performing coronary angiography on asymptomatic subjects, unlikely to gain prognostic benefit and unlikely to alter the study's findings, are unclear, especially with estimated morbidity and mortality rates of 1.8 and 0.08%, respectively.2
We thus stand by our conclusions and our developed normal range and would be happy for other authors to prospectively test them in other population groups.
References
- Kragelund C, Gronning B, Kober L, Hildebrandt P, Steffensen R. N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med 2005;352:666–675.
[Abstract/Free Full Text] - Bashore TM, Bates ER, Berger PB, Clark DA, Cusma JT, Dehmer GJ, Kern MJ, Laskey WK, O'Laughlin MP, Oesterle S, Popma JJ, O'Rourke RA, Abrams J, Bates ER, Brodie BR, Douglas PS, Gregoratos G, Hlatky MA, Hochman JS, Kaul S, Tracy CM, Waters DD, Winters WL Jr. American College of Cardiology/Society for Cardiac Angiography and Interventions Clinical Expert Consensus Document on Cardiac Catheterization Laboratory Standards. A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001;37:2170–2214.
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