Congestive Heart Failure Impact of age, race, and sex on the ability of B- type natriuretic peptide to aid in the emergency diagnosis of heart failure: Results from the Breathing Not Properly (BNP) multinational study Alan S. Maisel, MD, a Paul Clopton, MS, a Padma Krishnaswamy, MD, a Richard M. Nowak, MD, MBA, b James McCord, MD, b Judd E. Hollander, MD, c Philippe Duc, MD, d Torbjørn Omland, MD, PhD, e Alan B. Storrow, MD, f William T. Abraham, MD, g Alan H. B. Wu, PhD, h Gabriel Steg, MD, d Arne Westheim, MD, PhD, MPH, e Catherine Wold Knudsen, MD, e Alberto Perez, MD, h Radmila Kazanegra, MD, a Vikas Bhalla, MD, a Howard C. Herrmann, MD, c Marie Claude Aumont, MD, d and Peter A. McCullough, MD, MPH, i for the BNP Multinational Study Investigators† San Diego, Calif, Detroit, Mich, Philadelphia, Pa, Paris, France, Oslo, Norway, Cincinnati, Ohio, Lexington, Ky, Hartford, Conn, and Kansas City, Mo Background B-type natriuretic peptide (BNP) is secreted from the cardiac ventricles in response to increased wall tension. Methods The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who pre- sented to the Emergency Department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. The gold standard for congestive heart failure (CHF) was adjudicated by two independent cardiologists, blinded to BNP results, who reviewed all clinical data and standardized scores. The current study explores the effect of these variables on BNP decision statistics as well as the impact that changing cutoffs might have on the cost-effectiveness of diagnostic decisions that use BNP information. Results Significant differences in CHF rates were found on the basis of age (P  .001) and racial group (P = .020) but not sex (P = .424). BNP levels increased with increasing age (P  .001). To evaluate potential differences in the diagnostic utility of BNP levels as a function of demographic variables, separate receiver operating characteristic curves were performed. BNP was a stronger predictor in younger subjects than in older subjects and slightly weaker for female patients than for male patients (area under the curve = 0.918 and 0.870, respectively). An even smaller difference was noted between the white and black racial groups (area under the curve = 0.888 and 0.903, respectively). The differences in specificity as a function of age are larger than other differences in specificity or sensitivity. When logistic regression was used in a multivariate approach to combine the demographic variables with BNP information in the prediction of CHF, only BNP contributed significantly to the prediction of acute CHF. When the model was expanded to include terms for the interaction of each of the demographic vari- ables with log 10 BNP, a significant interaction was found for sex. Since the relative consequences of false-positives and false- negatives are unlikely to be equivalent, the BNP cut-points that would be selected based on the current data as a function of relative costs are presented. Sharply rising consequences are seen for BNP cut-points 100 pg/mL. Conclusions If one assumes that failing to treat cases of CHF is worse than treating negative cases, then relatively low BNP cut-points (eg, not 100 pg/mL) should be used in patients presenting to the Emergency Department with a chief complaint of dyspnea, regardless of age, sex, or ethnicity. (Am Heart J 2004;147:1078 – 84.) From the a University of California, San Diego, Veteran’s Affairs Medical Center, San Diego, Calif, b Henry Ford Hospital, Detroit, Mich, c University of Pennsylvania, Philadel- phia, Pa, d Hopital Bichat and Clinical Investigation Center, Paris, France, e Ullevål Uni- versity Hospital, Oslo, Norway, f University of Cincinnati College of Medicine, Cincin- nati, Ohio, g University of Kentucky College of Medicine, Lexington, Ky, h Hartford Hospital, Hartford, Conn, and the i University of Missouri-Kansas City School of Medi- cine, Truman Medical Center, Kansas City, Mo. Supported by Triage BNP devices and meters. Supported in part by Biosite, Incorporated, San Diego, Calif. Drs Maisel and McCullough have received honorariums from Biosite for speaking and consulting. Dr Kazanegra currently receives salary support from Biosite. Presented in part at the 51st Scientific Sessions of the American College of Cardiol- ogy, Atlanta, Ga, March 17, 2002. †See Appendix for author affiliations. Submitted September 14, 2003; accepted December 15, 2003. Reprint requests: Alan Maisel, MD, VAMC Cardiology 111-A, 3350 La Jolla Village Drive, San Diego, CA 92161. E-mail: amaisel@ucsd.edu 0002-8703/$ - see front matter © 2004, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2004.01.013