Correspondence
B-Type Natriuretic Peptide and Acute Coronary Syndromes
N Engl J Med 2002; 346:453-455February 7, 2002
- Article
To the Editor:
In their interesting study of the prognostic value of brain (B-type) natriuretic peptide in patients with acute coronary syndromes, de Lemos et al. (Oct. 4 issue)1 did not thoroughly assess the possible confounding effect of a well-established prognostic marker, C-reactive protein. The authors state that 2525 patients provided plasma samples for the measurement of B-type natriuretic peptide and that C-reactive protein was also measured in 925 of these patients. The authors report that the univariate analysis showed only a moderately strong association between the level of B-type natriuretic peptide and the level of C-reactive protein (r=0.2, P<0.001). They later affirm that B-type natriuretic peptide remained a significant independent prognostic factor in a multivariate logistic-regression analysis adjusted for several other independent predictors, including troponin I levels and ST-segment deviation. However, the multivariate analysis did not evaluate the possible role of C-reactive protein in the outcome-prediction model.
The important and independent role of C-reactive protein as a prognostic factor in patients with acute coronary syndromes, in both the short term and the long term, is now well established.2-5 We therefore believe that a thorough multivariate analysis of the 925 patients for whom data were available on both C-reactive protein and B-type natriuretic peptide levels could provide important information about the pathophysiological and clinical implications of neurohormonal activation and inflammation in unstable coronary syndromes, as well as defining the incremental role of B-type natriuretic peptide independently from the roles of the other available markers.
5 ReferencesGiuseppe G.L. Biondi-Zoccai, M.D.
Antonio Abbate, M.D.
Luigi M. Biasucci, M.D.
Catholic University of the Sacred Heart, 00168 Rome, Italy
gbiondizoccai@tiscalinet.it 1
de Lemos JA ,Morrow DA ,Bentley JH , et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001;345:1014-1021
Full Text | Web of Science | Medline2
Liuzzo G ,Biasucci LM ,Gallimore JR , et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994;331:417-424
Full Text | Web of Science | Medline3
Biasucci LM ,Liuzzo G ,Grillo RL , et al. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999;99:855-860
Web of Science | Medline4
Morrow DA ,Rifai N ,Antman EM , et al. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. J Am Coll Cardiol 1998;31:1460-1465
CrossRef | Web of Science | Medline5
Lindahl B ,Toss H ,Siegbahn A ,Venge P ,Wallentin L . Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. N Engl J Med 2000;343:1139-1147
Full Text | Web of Science | Medline
To the Editor:
Although the study by de Lemos and colleagues has important clinical implications, several points are worth highlighting. The authors state that patients with higher B-type natriuretic peptide levels had a greater number of stenosed coronary arteries than did patients with lower levels of the peptide, but they do not present data on the affected vessels. These data are relevant, since a previous study of B-type natriuretic peptide showed that patients with right coronary artery disease have both a lower plasma level at rest and a smaller increase in the level after exercise than do patients with left coronary artery disease.1 Higher levels of B-type natriuretic peptide may identify patients with left coronary artery disease — in particular, left anterior descending coronary artery disease — and this may explain the link between the peptide level and the prognosis.
The authors propose that a threshold of 80 pg per milliliter is an appropriate predictor of survival for patients with acute coronary syndromes. However, this level is derived from studies of heart failure. The optimal cutoff point may be lower in patients with acute coronary syndromes than in those with heart failure, since in the latter group, B-type natriuretic peptide levels are higher. Formal evaluation with the use of receiver-operating-characteristic curves to determine the optimal threshold for prognosis would have been more informative.
The investigators chose to evaluate a group of patients who went on to receive active treatment rather than placebo. A study of the placebo group might have been more valid, since the trial was terminated prematurely because of increased mortality in the active-treatment group.2
2 ReferencesPaul R. Kalra, M.R.C.P.
Rakesh Sharma, M.R.C.P.
National Heart and Lung Institute, London SW3 6LY, United Kingdom
p.kalra@ic. ac. uk Allan D. Struthers, M.D., F.R.C.P.
Ninewells Hospital, Dundee DD1 9SY, United Kingdom1
Davidson NC ,Pringle SD ,Pringle TH ,McNeill GP ,Struthers AD . Right coronary artery stenosis is associated with impaired cardiac endocrine function during exercise. Eur Heart J 1997;18:1749-1754
Web of Science | Medline2
Cannon CP ,McCabe CH ,Wilcox RG , et al. Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. Circulation 2000;102:149-156
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Biondi-Zoccai and colleagues state that C-reactive protein may have had a confounding effect on the association between B-type natriuretic peptide and mortality. Our multivariate model included only variables that could be evaluated in at least 75 percent of the patients.1 Because C-reactive protein was measured in only 925 of 2525 patients, it was not included in this model. However, when C-reactive protein was forced into an identical multivariate model that was limited to the 835 patients for whom complete data were available for all variables, including C-reactive protein, B-type natriuretic peptide remained an independent predictor of mortality at 10 months. The adjusted odds ratios for mortality at 10 months among patients with B-type natriuretic peptide levels in the second, third, and fourth quartiles (as compared with the first quartile) were 5.0 (95 percent confidence interval, 1.4 to 18.0), 4.0 (95 percent confidence interval, 1.1 to 14.1), and 6.0 (95 percent confidence interval, 1.8 to 20.4), respectively.
Kalra and colleagues raise three points. First, they note that B-type natriuretic peptide levels may be higher in patients with right-coronary-artery stenoses than in those with left-coronary-artery stenoses.1 This suggestion is plausible, since a larger myocardial territory is subtended by the left coronary artery, and a relation exists between the degree of ischemia and the magnitude of the elevation in the level of B-type natriuretic peptide.2 However, among the 1239 patients in our study for whom angiographic data were available, the B-type natriuretic peptide level was similar regardless of whether the culprit lesion was in the left anterior descending artery (115±139 pg per milliliter), the circumflex artery (100±97 pg per milliliter), or the right coronary artery (108±120 pg per milliliter).
Second, the authors ask whether a threshold lower than 80 pg per milliliter would be more appropriate for prognostic assessment in patients with acute coronary syndromes. We prospectively selected the threshold of 80 pg per milliliter to enhance the generalizability of our findings. Lower thresholds, evaluated retrospectively, do not appear to improve the overall predictive value as reflected by the chi-square test. Given the graded relation between the level of B-type natriuretic peptide and mortality in our analysis according to quartiles,3 a dichotomous threshold may not be the optimal approach to clinical application.
Finally, the authors suggest that it might have been more valid to study a placebo group rather than an active-treatment group. In the Oral Glycoprotein IIb/IIIa Inhibition with Orbofiban in Patients with Unstable Coronary Syndromes–Thrombolysis in Myocardial Infarction 16 trial, only one of the two active-treatment groups had excess mortality.4 In our study, we used only blood samples from the group of patients who received 50 mg of orbofiban for the duration of the study.3 Mortality in this group did not exceed that in the placebo group.4
4 ReferencesJames A. de Lemos, M.D.
University of Texas Southwestern Medical Center, Dallas, TX 75390-9034
james.delemos@utsouthwestern. edu David A. Morrow, M.D., M.P.H.
Eugene Braunwald, M.D.
Brigham and Women's Hospital, Boston, MA 021151
de Lemos JA ,Morrow DA ,Bentley JH , et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001;345:1014-1021
Full Text | Web of Science | Medline2
Davidson NC ,Pringle SD ,Pringle TH ,McNeill GP ,Struthers AD . Right coronary artery stenosis is associated with impaired cardiac endocrine function during exercise. Eur Heart J 1997;18:1749-1754
Web of Science | Medline3
Marumoto K ,Hamada M ,Hiwada K . Increased secretion of atrial and brain natriuretic peptides during acute myocardial ischaemia induced by dynamic exercise in patients with angina pectoris. Clin Sci (Lond) 1995;88:551-556
Web of Science | Medline4
Cannon CP ,McCabe CH ,Wilcox RG , et al. Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. Circulation 2000;102:149-156
Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Peiman Nazerian, Simone Vanni, Maurizio Zanobetti, Gianluca Polidori, Giuseppe Pepe, Roberto Federico, Elisabetta Cangioli, Stefano Grifoni. (2010) Diagnostic Accuracy of Emergency Doppler Echocardiography for Identification of Acute Left Ventricular Heart Failure in Patients with Acute Dyspnea: Comparison with Boston Criteria and N-terminal Prohormone Brain Natriuretic Peptide. Academic Emergency Medicine 17:1, 18-26
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