N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease

doi:10.1056/NEJMoa042330

Volume 352:666-675		February 17, 2005		Number 7

N-Terminal Pro–B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease

Charlotte Kragelund, M.D., Bjørn Grønning, M.D., Lars Køber, D.M.Sc., Per Hildebrandt, D.M.Sc., and Rolf Steffensen, M.D.

Full Text

PDF

PDA Full Text

PowerPoint Slide Set

Letters

Add to Personal Archive

Add to Citation Manager

Notify a Friend

E-mail When Cited

E-mail When Letters Appear

PubMed Citation

ABSTRACT

Background The level of the inactive N-terminal fragment ofpro–brain (B-type) natriuretic peptide (BNP) is a strongpredictor of mortality among patients with acute coronary syndromesand may be a strong prognostic marker in patients with chroniccoronary heart disease as well. We assessed the relationshipbetween N-terminal pro-BNP (NT-pro-BNP) levels and long-termmortality from all causes in a large cohort of patients withstable coronary heart disease.

Methods NT-pro-BNP was measured in baseline serum samples from1034 patients referred for angiography because of symptoms orsigns of coronary heart disease. The rate of death from allcauses was determined after a median follow-up of nine years.

Results At follow-up, 288 patients had died. The median NT-pro-BNPlevel was significantly lower among patients who survived thanamong those who died (120 pg per milliliter [interquartile range,50 to 318] vs. 386 pg per milliliter [interquartile range, 146to 897], P<0.001). Patients with NT-pro-BNP levels in thehighest quartile were older, had a lower left ventricular ejectionfraction (LVEF) and a lower creatinine clearance rate, and weremore likely to have a history of myocardial infarction, clinicallysignificant coronary artery disease, and diabetes than patientswith NT-pro-BNP levels in the lowest quartile. In a multivariableCox regression model, the hazard ratio for death from any causefor the patients with NT-pro-BNP levels in the fourth quartileas compared with those in the first quartile was 2.4 (95 percentconfidence interval, 1.5 to 4.0; P<0.001); the NT-pro-BNPlevel added prognostic information beyond that provided by conventionalrisk factors, including the patient's age; sex; family historywith respect to ischemic heart disease; the presence or absenceof a history of myocardial infarction, angina, hypertension,diabetes, or chronic heart failure; creatinine clearance rate;body-mass index; smoking status; plasma lipid levels; LVEF;and the presence or absence of clinically significant coronaryartery disease on angiography.

Conclusions NT-pro-BNP is a marker of long-term mortality inpatients with stable coronary disease and provides prognosticinformation above and beyond that provided by conventional cardiovascularrisk factors and the degree of left ventricular systolic dysfunction.

Source Information

From the Department of Cardiology and Endocrinology, Frederiksberg Hospital, Frederiksberg (C.K., B.G., P.H.); the Department of Cardiology, Rigshospitalet, Copenhagen (L.K.); and the Department of Cardiology, Hillerød University Hospital, Copenhagen (R.S.) — all in Denmark.

Address reprint requests to Dr. Kragelund at the Department of Cardiology and Endocrinology, Frederiksberg Hospital, University of Copenhagen, Nordre Fasanvej 57, DK-2000 Frederiksberg, Denmark, or at kragelund{at}dadlnet.dk.

Full Text of this Article

Related Letters:

N-Terminal Pro–B-Type Natriuretic Peptide and Mortality in Coronary Heart Disease
Pöge U., Gerhardt T. M., Woitas R. P., Kragelund C., Køber L., Hildebrandt P.
Extract | Full Text | PDF
N Engl J Med 2005; 352:2025-2026, May 12, 2005. Correspondence

This article has been cited by other articles:

Baggish, A L, Lloyd-Jones, D M, Blatt, J, Richards, A M, Lainchbury, J, O'Donoghue, M, Sakhuja, R, Chen, A A, Januzzi, J L (2008). A clinical and biochemical score for mortality prediction in patients with acute dyspnoea: derivation, validation and incorporation into a bedside programme. Heart 94: 1032-1037 [Abstract] [Full Text]
Winkler, K., Wanner, C., Drechsler, C., Lilienthal, J., Marz, W., Krane, V., for the German Diabetes and Dialysis Study Investi, (2008). Change in N-terminal-pro-B-type-natriuretic-peptide and the risk of sudden death, stroke, myocardial infarction, and all-cause mortality in diabetic dialysis patients. Eur Heart J 0: ehn278v1-8 [Abstract] [Full Text]
Roberts, M. A., Srivastava, P. M., Macmillan, N., Hare, D. L., Ratnaike, S., Sikaris, K., Ierino, F. L. (2008). B-type Natriuretic Peptides Strongly Predict Mortality in Patients Who Are Treated with Long-Term Dialysis. CJASN 3: 1057-1065 [Abstract] [Full Text]
Brune, K., Katus, H. A., Moecks, J., Spanuth, E., Jaffe, A. S., Giannitsis, E. (2008). N-Terminal Pro-B-Type Natriuretic Peptide Concentrations Predict the Risk of Cardiovascular Adverse Events from Antiinflammatory Drugs: A Pilot Trial. Clin. Chem. 54: 1149-1157 [Abstract] [Full Text]
Yip, G. W (2008). B-type natriuretic peptide: a treatment, not a diagnostic marker. Heart 94: 542-544 [Full Text]
West, M. J., Nestel, P. J., Kirby, A. C., Schnabel, R., Sullivan, D., Simes, R. J., Pollicino, C., Lubos, E., Munzel, T. F., White, H. D., Tonkin, A. M., Bickel, C., Tiret, L., Blankenberg, S., for the LIPID Study Investigators, (2008). The value of N-terminal fragment of brain natriuretic peptide and tissue inhibitor of metalloproteinase-1 levels as predictors of cardiovascular outcome in the LIPID study. Eur Heart J 29: 923-931 [Abstract] [Full Text]
Watz, H., Waschki, B., Boehme, C., Claussen, M., Meyer, T., Magnussen, H. (2008). Extrapulmonary Effects of Chronic Obstructive Pulmonary Disease on Physical Activity: A Cross-sectional Study. Am. J. Respir. Crit. Care Med. 177: 743-751 [Abstract] [Full Text]
Schnabel, R., Messow, C. M., Lubos, E., Espinola-Klein, C., Rupprecht, H. J., Bickel, C., Sinning, C., Tzikas, S., Keller, T., Genth-Zotz, S., Lackner, K. J., Munzel, T. F., Blankenberg, S. (2008). Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study. Eur Heart J 29: 649-657 [Abstract] [Full Text]
Paniagua, R., Amato, D., Mujais, S., Vonesh, E., Ramos, A., Correa-Rotter, R., Horl, W. H. (2008). Predictive Value of Brain Natriuretic Peptides in Patients on Peritoneal Dialysis: Results from the ADEMEX Trial. CJASN 3: 407-415 [Abstract] [Full Text]
Pitt, B. (2008). N-terminal pro-B-type natriuretic peptide concentrations >=100 ng/l increased risk of all-cause mortality. Evid. Based Med. 13: 26-26 [Full Text]
Daniels, L. B., Maisel, A. S. (2007). Natriuretic Peptides. J Am Coll Cardiol 50: 2357-2368 [Abstract] [Full Text]
Marchini, A., Hacker, B., Marttila, T., Hesse, V., Emons, J., Weiss, B., Karperien, M., Rappold, G. (2007). BNP is a transcriptional target of the short stature homeobox gene SHOX. Hum Mol Genet 16: 3081-3087 [Abstract] [Full Text]
Connolly, S.B., Collier, T., Khugputh, R., Tataree, D., Kyereme, K., Merritt, S., Struthers, A.D., Fox, K.F. (2007). Brain natriuretic peptide testing for angina in a rapid-access chest pain clinic. QJM 100: 779-783 [Abstract] [Full Text]
Kavsak, P. A., Ko, D. T., Newman, A. M., Palomaki, G. E., Lustig, V., MacRae, A. R., Jaffe, A. S. (2007). Risk Stratification for Heart Failure and Death in an Acute Coronary Syndrome Population Using Inflammatory Cytokines and N-Terminal Pro-Brain Natriuretic Peptide. Clin. Chem. 53: 2112-2118 [Abstract] [Full Text]
Pascual-Figal, D. A, Antolinos, M. J, Bayes-Genis, A., Casas, T., Nicolas, F., Valdes, M. (2007). B-type natriuretic peptide release in the coronary effluent after acute transient ischaemia in humans. Heart 93: 1077-1080 [Abstract] [Full Text]
Winkler, K., Hoffmann, M. M., Winkelmann, B. R., Friedrich, I., Schafer, G., Seelhorst, U., Wellnitz, B., Wieland, H., Boehm, B. O., Marz, W. (2007). Lipoprotein-Associated Phospholipase A2 Predicts 5-Year Cardiac Mortality Independently of Established Risk Factors and Adds Prognostic Information in Patients with Low and Medium High-Sensitivity C-Reactive Protein (The Ludwigshafen Risk and Cardiovascular Health Study). Clin. Chem. 53: 1440-1447 [Abstract] [Full Text]
Wilson Tang, W.H., Francis, G. S., Morrow, D. A., Newby, L. K., Cannon, C. P., Jesse, R. L., Storrow, A. B., Christenson, R. H., COMMITTEE MEMBERS, , Christenson, R. H., Apple, F. S., Cannon, C. P., Francis, G. S., Jesse, R. L., Morrow, D. A., Newby, L. K., Ravkilde, J., Storrow, A. B., Tang, W.H. W., Wu, A. H.B. (2007). National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure. Circulation 116: e99-e109 [Full Text]
Omland, T., Sabatine, M. S., Jablonski, K. A., Rice, M. M., Hsia, J., Wergeland, R., Landaas, S., Rouleau, J. L., Domanski, M. J., Hall, C., Pfeffer, M. A., Braunwald, E., for the PEACE Investigators, (2007). Prognostic Value of B-Type Natriuretic Peptides in Patients With Stable Coronary Artery Disease: The PEACE Trial. J Am Coll Cardiol 50: 205-214 [Abstract] [Full Text]
Struthers, A., Lang, C. (2007). The potential to improve primary prevention in the future by using BNP/N-BNP as an indicator of silent 'pancardiac' target organ damage: BNP/N-BNP could become for the heart what microalbuminuria is for the kidney. Eur Heart J 28: 1678-1682 [Abstract] [Full Text]
Shadman, R., Allison, M. A., Criqui, M. H. (2007). Glomerular Filtration Rate and N-Terminal Pro-Brain Natriuretic Peptide as Predictors of Cardiovascular Mortality in Vascular Patients. J Am Coll Cardiol 49: 2172-2181 [Abstract] [Full Text]
Voskaridou, E., Tsetsos, G., Tsoutsias, A., Spyropoulou, E., Christoulas, D., Terpos, E. (2007). Pulmonary hypertension in patients with sickle cell/{beta} thalassemia: incidence and correlation with serum N-terminal pro-brain natriuretic peptide concentrations. haematol 92: 738-743 [Abstract] [Full Text]
Marz, W., Tiran, B., Seelhorst, U., Wellnitz, B., Bauersachs, J., Winkelmann, B. R., Boehm, B. O. (2007). N-Terminal Pro-B-Type Natriuretic Peptide Predicts Total and Cardiovascular Mortality in Individuals with or without Stable Coronary Artery Disease: The Ludwigshafen Risk and Cardiovascular Health Study. Clin. Chem. 53: 1075-1083 [Abstract] [Full Text]
Fonarow, G. C., Peacock, W. F., Phillips, C. O., Givertz, M. M., Lopatin, M., for the ADHERE Scientific Advisory Committee and I, (2007). Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure. J Am Coll Cardiol 49: 1943-1950 [Abstract] [Full Text]
Jones, L. W., Haykowsky, M., Peddle, C. J., Joy, A. A., Pituskin, E. N., Tkachuk, L. M., Courneya, K. S., Slamon, D. J., Mackey, J. R. (2007). Cardiovascular Risk Profile of Patients with HER2/neu-Positive Breast Cancer Treated with Anthracycline-Taxane-Containing Adjuvant Chemotherapy and/or Trastuzumab. Cancer Epidemiol. Biomarkers Prev. 16: 1026-1031 [Abstract] [Full Text]
Sartipy, U., Albage, A., Larsson, P. T., Insulander, P., Lindblom, D. (2007). Changes in B-type natriuretic peptides after surgical ventricular restoration. Eur. J. Cardiothorac. Surg. 31: 922-928 [Abstract] [Full Text]
Lorgis, L., Zeller, M., Dentan, G., Sicard, P., Jolak, M., L'Huillier, I., Vincent-Martin, M., Beer, J.C., Makki, H., Gambert, P., Cottin, Y., on behalf of the RICO survey working group, (2007). High levels of N-terminal pro B-type natriuretic peptide are associated with ST resolution failure after reperfusion for acute myocardial infarction. QJM 100: 211-216 [Abstract] [Full Text]
Sekhri, N, Feder, G S, Junghans, C, Hemingway, H, Timmis, A D (2007). How effective are rapid access chest pain clinics? Prognosis of incident angina and non-cardiac chest pain in 8762 consecutive patients. Heart 93: 458-463 [Abstract] [Full Text]
Leuchte, H. H., El Nounou, M., Tuerpe, J. C., Hartmann, B., Baumgartner, R. A., Vogeser, M., Muehling, O., Behr, J. (2007). N-terminal Pro-Brain Natriuretic Peptide and Renal Insufficiency as Predictors of Mortality in Pulmonary Hypertension. Chest 131: 402-409 [Abstract] [Full Text]
Feringa, H. H H, Schouten, O., Dunkelgrun, M., Bax, J. J, Boersma, E., Elhendy, A., de Jonge, R., Karagiannis, S. E, Vidakovic, R., Poldermans, D. (2007). Plasma N-terminal pro-B-type natriuretic peptide as long-term prognostic marker after major vascular surgery. Heart 93: 226-231 [Abstract] [Full Text]
Schou, M., Gustafsson, F., Kjaer, A., Hildebrandt, P. R. (2007). Long-term clinical variation of NT-proBNP in stable chronic heart failure patients. Eur Heart J 0: ehl449v1-6 [Abstract] [Full Text]
Bibbins-Domingo, K., Gupta, R., Na, B., Wu, A. H. B., Schiller, N. B., Whooley, M. A. (2007). N-Terminal Fragment of the Prohormone Brain-Type Natriuretic Peptide (NT-proBNP), Cardiovascular Events, and Mortality in Patients With Stable Coronary Heart Disease. JAMA 297: 169-176 [Abstract] [Full Text]
Konstam, M. A. (2007). Natriuretic Peptides and Cardiovascular Events: More Than a Stretch. JAMA 297: 212-214 [Full Text]
Wang, T. J., Gona, P., Larson, M. G., Tofler, G. H., Levy, D., Newton-Cheh, C., Jacques, P. F., Rifai, N., Selhub, J., Robins, S. J., Benjamin, E. J., D'Agostino, R. B., Vasan, R. S. (2006). Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death. NEJM 355: 2631-2639 [Abstract] [Full Text]
de Lemos, J. A. (2006). The Latest and Greatest New Biomarkers: Which Ones Should We Measure for Risk Prediction in Our Practice?. Arch Intern Med 166: 2428-2430 [Full Text]
Rothenbacher, D., Koenig, W., Brenner, H. (2006). Comparison of N-Terminal Pro-B-Natriuretic Peptide, C-Reactive Protein, and Creatinine Clearance for Prognosis in Patients With Known Coronary Heart Disease. Arch Intern Med 166: 2455-2460 [Abstract] [Full Text]
Giallauria, F., Lucci, R., De Lorenzo, A., D'Agostino, M., Del Forno, D., Vigorito, C. (2006). Favourable effects of exercise training on N-terminal pro-brain natriuretic peptide plasma levels in elderly patients after acute myocardial infarction. Age Ageing 35: 601-607 [Abstract] [Full Text]
Klein, G., Lissel, C., Fuchs, A.-C., Gardiwal, A., Oswald, H., deSousa, M., Pichlmaier, A. M., Lichtinghagen, R., Geerlings, H., Lippolt, P., Niehaus, M., Drexler, H., Korte, T. (2006). Predictors of VT/VF-occurrence in ICD patients: results from the PROFIT-Study.. Europace 8: 618-624 [Abstract] [Full Text]
Machado, R. F., Anthi, A., Steinberg, M. H., Bonds, D., Sachdev, V., Kato, G. J., Taveira-DaSilva, A. M., Ballas, S. K., Blackwelder, W., Xu, X., Hunter, L., Barton, B., Waclawiw, M., Castro, O., Gladwin, M. T., for the MSH Investigators, (2006). N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease.. JAMA 296: 310-318 [Abstract] [Full Text]
Kistorp, C. (2006). Risk Stratification in Secondary Prevention: Advances in Multimarker Profiles, or Back to Basics?. Circulation 114: 184-186 [Full Text]
Hammerer-Lercher, A., Geiger, R., Mair, J., Url, C., Tulzer, G., Lechner, E., Puschendorf, B., Sommer, R. (2006). Utility of N-Terminal Pro-B-Type Natriuretic Peptide to Differentiate Cardiac Diseases from Noncardiac Diseases in Young Pediatric Patients. Clin. Chem. 52: 1415-1419 [Abstract] [Full Text]
Kragelund, C., Gustafsson, I., Omland, T., Gronning, B., Kober, L., Faber, J., Strande, S., Steffensen, R., Hildebrandt, P. (2006). Prognostic Value of NH2-Terminal Pro B-Type Natriuretic Peptide in Patients With Diabetes and Stable Coronary Heart Disease.. Diabetes Care 29: 1411-1413 [Full Text]
Weber, M., Hamm, C. (2006). Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine.. Heart 92: 843-849 [Full Text]
Authors/Task Force Members, , Fox, K., Garcia, M. A. A., Ardissino, D., Buszman, P., Camici, P. G., Crea, F., Daly, C., De Backer, G., Hjemdahl, P., Lopez-Sendon, J., Marco, J., Morais, J., Pepper, J., Sechtem, U., Simoons, M., Thygesen, K., ESC Committee for Practice Guidelines (CPG), , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, J., Dean, V., Deckers, J., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J., Zamorano, J. L., Document Reviewers, , Zamorano, J. L, Andreotti, F., Becher, H., Dietz, R., Fraser, A., Gray, H., Antolin, R. A. H., Huber, K., Kremastinos, D. T., Maseri, A., Nesser, H.-J., Pasierski, T., Sigwart, U., Tubaro, M., Weis, M. (2006). Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 27: 1341-1381 [Full Text]
Almog, Y., Novack, V., Megralishvili, R., Kobal, S., Barski, L., King, D., Zahger, D. (2006). Plasma level of N terminal pro-brain natriuretic Peptide as a prognostic marker in critically ill patients.. Anesth. Analg. 102: 1809-1815 [Abstract] [Full Text]
Vasan, R. S. (2006). Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations. Circulation 113: 2335-2362 [Full Text]
Minoretti, P., Falcone, C., Calcagnino, M., Emanuele, E., Buzzi, M. P., Coen, E., Geroldi, D. (2006). Prognostic significance of plasma osteopontin levels in patients with chronic stable angina. Eur Heart J 27: 802-807 [Abstract] [Full Text]
Wolber, T., Maeder, M. (2006). Normal range of N-terminal pro-brain natriuretic peptide: a note of caution. Eur Heart J 27: 622-622 [Full Text]
Galasko, G., Senior, R. (2006). Normal range of N-terminal pro-brain natriuretic peptide: a note of caution: reply. Eur Heart J 27: 622-623 [Full Text]
Januzzi, J. L. Jr, Sakhuja, R., O'Donoghue, M., Baggish, A. L., Anwaruddin, S., Chae, C. U., Cameron, R., Krauser, D. G., Tung, R., Camargo, C. A. Jr, Lloyd-Jones, D. M. (2006). Utility of amino-terminal pro-brain natriuretic Peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department.. Arch Intern Med 166: 315-320 [Abstract] [Full Text]
Schnabel, R., Lubos, E., Rupprecht, H. J., Espinola-Klein, C., Bickel, C., Lackner, K. J., Cambien, F., Tiret, L., Munzel, T., Blankenberg, S. (2006). B-Type Natriuretic Peptide and the Risk of Cardiovascular Events and Death in Patients With Stable Angina: Results From the AtheroGene Study. J Am Coll Cardiol 47: 552-558 [Abstract] [Full Text]
De Sutter, J., De Bacquer, D., Cuypers, S., Delanghe, J., De Buyzere, M., Kornitzer, M., De Backer, G. (2005). Plasma N-terminal pro-brain natriuretic peptide concentration predicts coronary events in men at work: a report from the BELSTRESS study. Eur Heart J 26: 2644-2649 [Abstract] [Full Text]
Goetze, J. P. (2005). Coronary artery disease, heart failure, and cardiac natriuretic peptides in the middle. Eur Heart J 26: 2603-2604 [Full Text]
Schou, M., Dalsgaard, M. K., Clemmesen, O., Dawson, E. A., Yoshiga, C. C., Nielsen, H. B., Gustafsson, F., Hildebrandt, P. R., Secher, N. H. (2005). Kidneys extract BNP and NT-proBNP in healthy young men. J. Appl. Physiol. 99: 1676-1680 [Abstract] [Full Text]
Ginsburg, G. S., Donahue, M. P., Newby, L. K. (2005). Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics. J Am Coll Cardiol 46: 1615-1627 [Abstract] [Full Text]
Conti, E., Volpe, M., Carrozza, C., Marzo, F., Zuppi, C., Crea, F., Andreotti, F. (2005). Pregnancy-Associated Plasma Protein-A and Acute Coronary Syndromes: Cause or Consequence?. J Am Coll Cardiol 46: 1583-1584 [Full Text]
Ndrepepa, G., Braun, S., Niemoller, K., Mehilli, J., von Beckerath, N., von Beckerath, O., Vogt, W., Schomig, A., Kastrati, A. (2005). Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide in Patients With Chronic Stable Angina. Circulation 112: 2102-2107 [Abstract] [Full Text]
(2005). Other articles noted. Evid. Based Med. 10: 157-158 [Full Text]
Struthers, A.D., Davies, J. (2005). B-type natriuretic peptide: a simple new test to identify coronary artery disease?. QJM 98: 765-769 [Abstract] [Full Text]
Mockel, M., Muller, R., Vollert, J. O., Muller, C., Carl, A., Peetz, D., Post, F., Kohse, J. K., Lackner, K. J. (2005). Role of N-Terminal Pro-B-Type Natriuretic Peptide in Risk Stratification in Patients Presenting in the Emergency Room. Clin. Chem. 51: 1624-1631 [Abstract] [Full Text]
Abrams, J. (2005). Chronic Stable Angina. NEJM 352: 2524-2533 [Full Text]
Poge, U., Gerhardt, T. M., Woitas, R. P., Kragelund, C., Kober, L., Hildebrandt, P. (2005). N-Terminal Pro-B-Type Natriuretic Peptide and Mortality in Coronary Heart Disease. NEJM 352: 2025-2026 [Full Text]
(2005). N-Terminal pro-BNP Predicts Death in Stable CAD. Journal Watch Cardiology 2005: 3-3 [Full Text]
Malik, I. (2005). JournalScan. Heart 91: 703-704 [Full Text]
(2005). Another Predictor of Mortality in Patients with Coronary Disease. JWatch General 2005: 1-1 [Full Text]

Comments and questions? Please contact us.