To the Editor:—
We read with great interest the research article by Fox et al.1
on genetic variation within defined regions of the NPPA
natriuretic peptide system genes as predictors for ventricular dysfunction after coronary artery bypass graft surgery. What concerns us as clinicians is the relation between those biomarkers and postoperative outcome, which can facilitate the preoperative risk evaluation. This article raised a good question: whether B-type natriuretic peptide (BNP) or its gene polymorphism predicts the prognosis in patients undergoing coronary artery bypass graft surgery.
It is well known that a gene's function is mediated by expression of a specific protein. BNP has been established as a prognostic indicator in adults with congestive heart failure2
and coronary artery disease,3
whereas single nucleotide polymorphisms (SNPs) in the NPPB
gene significantly impact BNP levels.4
In the article by Dr. Fox et al.
, there was mention that genetic variation within NPPA
genes was associated with risk of ventricular dysfunction after adjustment for preoperative BNP level and clinical factors. However, the authors did not directly analyze the relation between SNPs of these BNP genes with BNP level, especially postoperative BNP, whose level was not provided. Previous study has shown that early postoperative BNP levels correlate significantly with the ensuing duration of inotropic support and duration of hospitalization.5
Therefore, we considered that SNPs of BNP genes could affect postoperative BNP rather than preoperative BNP and then predicted the prognosis, because expression of those genetic loci could be up- or down-regulated by mechanical stretch, ischemic injury, hypoxia, or even inflammatory mediators during surgery.6
And the analysis should include both preoperative and postoperative BNP levels in this study.
We think that the predictive pathway should be: SNPs of BNP–BNP level–clinical prognosis. If this hypothesis is established, it is postoperative BNP rather than SNPs of BNP that directly predicts ventricular dysfunction. Further investigations are still required to elucidate how BNP and its SNPs relate to development of postoperative ventricular dysfunction.
Hai Yu, M.D.
Da Zhu, M.D.
Bin Liu, M.D.*
*West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. firstname.lastname@example.org
1. Fox AA, Collard CD, Shernan SK, Seidman CE, Seidman JG, Liu KY, Muehlschlegel JD, Perry TE, Aranki SF, Lange C, Herman DS, Meitinger T, Lichtner P, Body SC: Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting. Anesthesiology 2009; 110:738–47
2. Doust JA, Pietrzak E, Dobson A, Glasziou P: How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: Systematic review. BMJ 2005; 330:625
3. 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; 352:666–75
4. Lanfear DE, Stolker JM, Marsh S, Rich MW, McLeod HL: Genetic variation in the B-type natriuretic peptide pathway affect BNP levels. Cardiovasc Drugs Ther 2007; 21:55–62
5. Berry JG, Askovich B, Shaddy RE, Hawkins JA, Cowley CG: Prognostic value of B-type natriuretic peptide in surgical palliation of children with single-ventricle congenital heart disease. Pediatr Cardiol 2008; 29:70–5
6. Martinez-Rumayor A, Richards AM, Burnett JC, Januzzi JL Jr: Biology of the natriuretic peptides. Am J Cardiol 2008; 101:3–8
© 2009 American Society of Anesthesiologists, Inc.