(Circulation. 2005;111:e15-e16.)
© 2005 American Heart Association, Inc.
Correspondence |
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
We read the correspondence1 about the article by Bibbins-Domingo et al2 with great interest. The report by Bibbins-Domingo et al2 demonstrated elevated plasma concentrations of B-type natriuretic peptide (BNP) associated with inducible ischemia in patients with stable coronary artery disease. In contrast, Nishikimi and Matsuoka1 suggested that N-terminal proANP (atrial natriuretic peptide) might be a more sensitive plasma marker of stable coronary artery disease than are ANP and BNP. We recently measured the plasma concentrations of BNP as well as its biosynthetic precursor, proBNP, in patients with coronary artery disease and normal left ventricular systolic function.3 Both BNP and proBNP were markedly elevated (5- and 10-fold, respectively) in those patients as compared with individuals without coronary artery disease. Moreover, the BNP and proBNP plasma concentrations were closely associated. Interestingly, within a group of patients undergoing coronary artery bypass surgery, the extent of elevation of both plasma BNP and proBNP concentrations in each patient was positively associated with the ventricular BNP mRNA content.3 These data suggest that both BNP and proBNP are sensitive markers of chronic cardiac ischemia and that the elevated plasma concentrations reflect an increased BNP gene transcription. In studies of pigs, we recently found that even acute cardiac hypoxia induces BNP gene expression in the ventricular myocardium and an increase of the plasma proBNP concentration.4 Moreover, only proBNP (not BNP) was rapidly released from ventricular myocytes when subjected to hypoxia in vitro.4 These experimental data are in accord with another recent clinical observation that coronary arteriography results in a rapid but transient rise in the plasma proBNP but not BNP concentrations.5
We suggest that plasma measurement of both BNP and proBNP is useful in detecting chronic ischemia associated with coronary artery disease, whereas proBNP may be a more sensitive marker of acute cardiac ischemia.
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1. Nishikimi T, Matsuoka H. Are plasma levels of atrial natriuretic peptide, N-terminal ProANP, and brain natriuretic peptide affected by the presence of coronary artery disease? Circulation. 2004; 109: e331.
2. Bibbins-Domingo K, Ansari M, Schiller NB, Massie B, Whooley MA. B-type natriuretic peptide and ischemia in patients with stable coronary disease: data from the Heart and Soul study. Circulation. 2003; 108: 2987–2992.
3. Goetze JP, Christoffersen C, Perko M, Arendrup H, Rehfeld JF, Kastrup J, Nielsen LB. Increased cardiac BNP expression associated with myocardial ischemia. FASEB J. 2003; 17: 1105–1107.
4. Goetze JP, Gore A, Møller CH, Steinbrüchel DA, Rehfeld JF, Nielsen LB. Acute myocardial hypoxia increases BNP gene expression. FASEB J. 2004; 18: 1928–1930.
5. Goetze JP, Yongzhong W, Rehfeld JF, Jorgensen E, Kastrup J. Coronary angiography transiently increases plasma pro-B-type natriuretic peptide. Eur Heart J. 2004; 25: 759–764.
Response
Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Tochigi, Japan
We thank Drs Nielsen and Goetze for their interest in our recently published correspondence.1 In our study, we measured levels of N-terminal proatrial natriuretic peptide (N-ANP), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in patients with normal left ventricular function (ejection fraction 
60%) who were suspected of having coronary artery disease (CAD).1,2 Our main objective was to determine whether coronary artery stenosis affects plasma natriuretic peptide levels. Our findings suggested that N-ANP is associated with the presence of coronary artery stenosis in patients with normal left ventricular systolic function because transient myocardial ischemia stimulates the secretion of ANP and N-ANP3 and increased plasma N-ANP levels may last for a longer time than ANP because the former has a longer half-life.
Goetze et al4 showed that plasma BNP and proBNP levels are higher than controls in patients who have CAD with normal systolic function. Although left ventricular ejection fraction (LVEF) was similar in the CAD and the control groups in their study, the CAD group included patients with an LVEF of 
50 (5 of 13 patients undergoing CABG and 5 of 10 undergoing percutaneous coronary intervention). The figures seem to indicate that patients with good systolic function (LVEF 60%) had normal BNP levels and low BNP mRNA levels. Thus, plasma BNP and proBNP levels may increase in patients with minimal degrees of impaired systolic function, wall motion abnormality, or both. In these patients, hypoxia may be an important stimulus for BNP mRNA expression, as Goetze et al suggest.
Thus, ANP, N-ANP, BNP, and proBNP all are useful biochemical markers for cardiovascular diseases, including CAD, but their clinical implications differ slightly because they have different sites of production, mechanisms of release, and metabolic characteristics.
Finally, we would like to comment on the plasma BNP levels measured by Goetze et al4 using a Shionoria BNP kit (Shionogi Inc). This kit uses 2 monoclonal antibodies, which recognize the ring structure and carboxyterminal sequence. Therefore, BNP levels measured with this kit indicate the sum of BNP (77–108) plus proBNP(1–108,) not BNP (77–108) alone.
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References |
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TopReferencesReferences |
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1. Nishikimi T, Matsuoka H. Are plasma levels of atrial natriuretic peptide, N-terminal ProANP, and brain natriuretic peptide affected by the presence of coronary artery disease? Circulation. 2004; 109: e331.
2. Nishikimi T, Mori Y, Ishimura K, Tadokoro K, Yagi H, Yabe A, Horinaka S, Matsuoka H. Association of plasma atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, and brain natriuretic peptide levels with coronary artery stenosis in patients with normal left ventricular systolic function. Am J Med. 2004; 116: 517–523.[CrossRef][Medline] [Order article via Infotrieve]
3. Malatino LS, Leonardi C, Stancanelli B, Polizzi G, Grassi R, Tamburino C, Tamburino G. Transient myocardial ischemia stimulates atrial natriuretic factor release. Am Heart J. 1992; 123: 693–698.[CrossRef][Medline] [Order article via Infotrieve]
4. Goetze JP, Christoffersen C, Perko M, Arendrup H, Rehfeld JF, Kastrup J, Nielsen LB. Increased cardiac BNP expression associated with myocardial ischemia. FASEB J. 2003; 17: 1105–1107.
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