Role of B-Type Natriuretic Peptide and N-Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

Emil Wolsk, Brian Claggett, Marc A Pfeffer, Rafael Diaz, Kenneth Dickstein, Hertzel C Gerstein, Francesca C Lawson, Eldrin F Lewis, Aldo P Maggioni, John J V McMurray, Jeffrey L Probstfield, Matthew C Riddle, Scott D Solomon, Jean-Claude Tardif, Lars Køber, Emil Wolsk, Brian Claggett, Marc A Pfeffer, Rafael Diaz, Kenneth Dickstein, Hertzel C Gerstein, Francesca C Lawson, Eldrin F Lewis, Aldo P Maggioni, John J V McMurray, Jeffrey L Probstfield, Matthew C Riddle, Scott D Solomon, Jean-Claude Tardif, Lars Køber

Abstract

Background: Natriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B-type natriuretic peptide (BNP) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus.

Methods and results: Patients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow-up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/NT-proBNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT-proBNP to best risk models. Overall, BNP and NT-proBNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77-0.82, P<0.001), cardiovascular death (0.77-0.83, P<0.001), and heart failure (0.84-0.87, P<0.001). BNP or NT-proBNP alone predicted death as well as all other variables combined (0.77 versus 0.77).

Conclusions: In patients with a recent acute coronary syndrome and type 2 diabetes mellitus, BNP and NT-proBNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01147250.

Keywords: Evaluation of Lixisenatide in Acute Coronary Syndrome trial; N‐terminal prohormone B‐type natriuretic peptide; acute coronary syndrome; biomarker; brain natriuretic peptide; cardiac outcomes; diabetes mellitus; glucagon‐like peptide‐1; natriuretic peptide; risk model.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
The association of BNP and NT‐proBNP concentrations and risk of all‐cause death. The hazard of death is depicted with 95% CIs. The reference of hazard ratio=1.0 corresponds to a BNP concentration of 35 pg/mL, and a NT‐proBNP concentration of 125 pg/mL. BNP indicates B‐type natriuretic peptide; NT‐proBNP, N‐terminal prohormone BNP.

References

    1. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234.
    1. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002;287:2570–2581.
    1. Scirica BM, Kadakia MB, de Lemos JA, Roe MT, Morrow DA, Li S, Wiviott SD, Kontos MC. Association between natriuretic peptides and mortality among patients admitted with myocardial infarction: a report from the ACTION Registry®–GWTGTM . Clin Chem. 2013;59:1205–1214.
    1. Jhund PS, Anand IS, Komajda M, Claggett BL, McKelvie RS, Zile MR, Carson PE, McMurray JJV. Changes in N‐terminal pro‐B‐type natriuretic peptide levels and outcomes in heart failure with preserved ejection fraction: an analysis of the I‐Preserve study. Eur J Heart Fail. 2015;17:809–817.
    1. Kristensen SL, Jhund PS, Køber L, McKelvie RS, Zile MR, Anand IS, Komajda M, Cleland JGF, Carson PE, McMurray JJV. Relative importance of history of heart failure hospitalization and N‐terminal pro‐B‐type natriuretic peptide level as predictors of outcomes in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2015;3:478–486.
    1. Lourenço P, Ribeiro A, Pintalhão M, Silva S, Bettencourt P. Predictors of six‐month mortality in BNP‐matched acute heart failure patients. Am J Cardiol. 2015;116:744–748.
    1. Berger R, Huelsman M, Strecker K, Bojic A, Moser P, Stanek B, Pacher R. B‐type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation. 2002;105:2392–2397.
    1. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S; CHARM Investigators and Committees . Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM‐Overall programme. Lancet. 2003;362:759–766.
    1. Pfeffer MA, McMurray JJV, Velazquez EJ, Rouleau J‐L, Køber L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM; Valsartan in Acute Myocardial Infarction Trial Investigators . Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349:1893–1906.
    1. Omland T, Aakvaag A, Bonarjee VV, Caidahl K, Lie RT, Nilsen DW, Sundsfjord JA, Dickstein K. Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long‐term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N‐terminal proatrial natriuretic peptide. Circulation. 1996;93:1963–1969.
    1. Mega JL, Morrow DA, De Lemos JA, Sabatine MS, Murphy SA, Rifai N, Gibson CM, Antman EM, Braunwald E. B‐type natriuretic peptide at presentation and prognosis in patients with ST‐segment elevation myocardial infarction: an ENTIRE‐TIMI‐23 substudy. J Am Coll Cardiol. 2004;44:335–339.
    1. Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Demopoulos LA, DiBattiste PM, McCabe CH, Gibson CM, Cannon CP, Braunwald E. Evaluation of B‐type natriuretic peptide for risk assessment in unstable angina/non‐ST‐elevation myocardial infarction: B‐type natriuretic peptide and prognosis in TACTICS‐TIMI 18. J Am Coll Cardiol. 2003;41:1264–1272.
    1. Scirica BM, Bhatt DL, Braunwald E, Raz I, Cavender MA, Im K, Mosenzon O, Udell JA, Hirshberg B, Pollack PS, Steg PG, Jarolim P, Morrow DA. Prognostic implications of biomarker assessments in patients with type 2 diabetes at high cardiovascular risk: a secondary analysis of a randomized clinical trial. JAMA Cardiol. 2016;1:989–998.
    1. James SK, Lindahl B, Siegbahn A, Stridsberg M, Venge P, Armstrong P, Barnathan ES, Califf R, Topol EJ, Simoons ML, Wallentin L. N‐terminal pro‐brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)‐IV substudy. Circulation. 2003;108:275–281.
    1. Sabatine MS, Morrow DA, de Lemos JA, Omland T, Desai MY, Tanasijevic M, Hall C, McCabe CH, Braunwald E. Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia. J Am Coll Cardiol. 2004;44:1988–1995.
    1. Wiersma JJ, van der Zee PM, van Straalen JP, Fischer JC, van Eck‐Smit BLF, Tijssen JGP, Trip MD, Piek JJ, Verberne HJ. NT‐pro‐BNP is associated with inducible myocardial ischemia in mildly symptomatic type 2 diabetic patients. Int J Cardiol. 2010;145:295–296.
    1. Wachter R, Lahno R, Haase B, Weber‐Krüger M, Seegers J, Edelmann F, Wohlfahrt J, Gelbrich G, Görlitz A, Kermer P, Vollmann D, Hasenfuß G, Gröschel K, Stahrenberg R. Natriuretic peptides for the detection of paroxysmal atrial fibrillation in patients with cerebral ischemia—the Find‐AF Study. PLoS One. 2012;7:e34351.
    1. Sinner MF, Stepas KA, Moser CB, Krijthe BP, Aspelund T, Sotoodehnia N, Fontes JD, Janssens ACJW, Kronmal RA, Magnani JW, Witteman JC, Chamberlain AM, Lubitz SA, Schnabel RB, Vasan RS, Wang TJ, Agarwal SK, McManus DD, Franco OH, Yin X, Larson MG, Burke GL, Launer LJ, Hofman A, Levy D, Gottdiener JS, Kääb S, Couper D, Harris TB, Astor BC, Ballantyne CM, Hoogeveen RC, Arai AE, Soliman EZ, Ellinor PT, Stricker BHC, Gudnason V, Heckbert SR, Pencina MJ, Benjamin EJ, Alonso A. B‐type natriuretic peptide and C‐reactive protein in the prediction of atrial fibrillation risk: the CHARGE‐AF Consortium of community‐based cohort studies. Europace. 2014;16:1426–1433.
    1. Omland T, Sabatine MS, Jablonski KA, Rice MM, Hsia J, Wergeland R, Landaas S, Rouleau JL, Domanski MJ, Hall C, Pfeffer MA, Braunwald E; PEACE Investigators . Prognostic value of B‐type natriuretic peptides in patients with stable coronary artery disease: the PEACE Trial. J Am Coll Cardiol. 2007;50:205–214.
    1. Blankenberg S. Comparative impact of multiple biomarkers and N‐terminal pro‐brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation. 2006;114:201–208.
    1. Mishra RK, Beatty AL, Jaganath R, Regan M, Wu AHB, Whooley MA. B‐type natriuretic peptides for the prediction of cardiovascular events in patients with stable coronary heart disease: the Heart and Soul Study. J Am Heart Assoc. 2014;3:e000907 DOI: .
    1. Eggers KM, Kempf T, Venge P, Wallentin L, Wollert KC, Lindahl B. Improving long‐term risk prediction in patients with acute chest pain: the Global Registry of Acute Coronary Events (GRACE) risk score is enhanced by selected nonnecrosis biomarkers. Am Heart J. 2010;160:88–94.
    1. Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, Lawson FC, Ping L, Wei X, Lewis EF, Maggioni AP, McMurray JJV, Probstfield JL, Riddle MC, Solomon SD, Tardif J‐C; ELIXA Investigators . Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247–2257.
    1. Bentley‐Lewis R, Aguilar D, Riddle MC, Claggett B, Diaz R, Dickstein K, Gerstein HC, Johnston P, Køber LV, Lawson F, Lewis EF, Maggioni AP, McMurray JJV, Ping L, Probstfield JL, Solomon SD, Tardif J‐C, Wu Y, Pfeffer MA; ELIXA Investigators . Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long‐term cardiovascular end point trial of lixisenatide versus placebo. Am Heart J. 2015;169:631–638.e7.
    1. McMurray JJV, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez‐Sanchez MA, Jaarsma T, Køber L, Lip GYH, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology , Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck‐Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P; ESC Committee for Practice Guidelines . ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–869.
    1. Pfeffer MA, Burdmann EA, Chen C‐Y, Cooper ME, de Zeeuw D, Eckardt K‐U, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJV, Parfrey P, Parving H‐H, Remuzzi G, Singh AK, Solomon SD, Toto R; TREAT Investigators . A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361:2019–2032.
    1. Intensive blood‐glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–853.
    1. McMurray JJV, Uno H, Jarolim P, Desai AS, de Zeeuw D, Eckardt K‐U, Ivanovich P, Levey AS, Lewis EF, McGill JB, Parfrey P, Parving H‐H, Toto RM, Solomon SD, Pfeffer MA. Predictors of fatal and nonfatal cardiovascular events in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia: an analysis of the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin‐alfa) Therapy (TREAT). Am Heart J. 2011;162:748–755.e3.
    1. Stevens RJ, Kothari V, Adler AI, Stratton IM; United Kingdom Prospective Diabetes Study (UKPDS) Group . The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56). Clin Sci (Lond). 2001;101:671–679.
    1. Masson S, Latini R, Anand IS, Vago T, Angelici L, Barlera S, Missov ED, Clerico A, Tognoni G, Cohn JN; Val‐HeFT Investigators . Direct comparison of B‐type natriuretic peptide (BNP) and amino‐terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val‐HeFT) data. Clin Chem. 2006;52:1528–1538.
    1. Luchner A, Behrens G, Stritzke J, Markus M, Stark K, Peters A, Meisinger C, Leitzmann M, Hense H‐W, Schunkert H, Heid IM. Long‐term pattern of brain natriuretic peptide and N‐terminal pro brain natriuretic peptide and its determinants in the general population: contribution of age, gender, and cardiac and extra‐cardiac factors. Eur J Heart Fail. 2013;15:859–867.
    1. Peng Q, Hu W, Su H, Yang Q, Cheng X. Levels of B‐type natriuretic peptide in chronic heart failure patients with and without diabetes mellitus. Exp Ther Med. 2013;5:229–232.
    1. Lindahl B, Lindbäck J, Jernberg T, Johnston N, Stridsberg M, Venge P, Wallentin L. Serial analyses of N‐terminal pro‐B‐type natriuretic peptide in patients with non‐ST‐segment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)‐II substudy. J Am Coll Cardiol. 2005;45:533–541.
    1. White M, Rouleau JL, Hall C, Arnold M, Harel F, Sirois P, Greaves S, Solomon S, Ajani U, Glynn R, Hennekens C, Pfeffer M. Changes in vasoconstrictive hormones, natriuretic peptides, and left ventricular remodeling soon after anterior myocardial infarction. Am Heart J. 2001;142:1056–1064.
    1. Sandhu S, Har BJ, Aggarwal SG, Kavanagh KM, Ramadan D, Exner DV; REFINE Investigators . Predictive value of repeated versus single N‐terminal pro B‐type natriuretic peptide measurements early after‐myocardial infarction. Pacing Clin Electrophysiol. 2009;32(suppl 1):S86–S89.
    1. Fertin M, Hennache B, Hamon M, Ennezat PV, Biausque F, Elkohen M, Nugue O, Tricot O, Lamblin N, Pinet F, Bauters C. Usefulness of serial assessment of B‐type natriuretic peptide, troponin I, and C‐reactive protein to predict left ventricular remodeling after acute myocardial infarction (from the REVE‐2 study). Am J Cardiol. 2010;106:1410–1416.
    1. Wannamethee SG, Welsh P, Lowe GD, Gudnason V, Di Angelantonio E, Lennon L, Rumley A, Whincup PH, Sattar N. N‐terminal pro‐brain natriuretic peptide is a more useful predictor of cardiovascular disease risk than C‐reactive protein in older men with and without pre‐existing cardiovascular disease. J Am Coll Cardiol. 2011;58:56–64.
    1. Pfister R, Tan D, Thekkanal J, Hellmich M, Erdmann E, Schneider CA. NT‐pro‐BNP measured at discharge predicts outcome in multimorbid diabetic inpatients with a broad spectrum of cardiovascular disease. Acta Diabetol. 2007;44:91–97.
    1. James SK, Lindahl B, Timmer JR, Ottervanger JP, Siegbahn A, Stridsberg M, Armstrong P, Califf R, Wallentin L, Simoons ML. Usefulness of biomarkers for predicting long‐term mortality in patients with diabetes mellitus and non‐ST‐elevation acute coronary syndromes (a GUSTO IV substudy). Am J Cardiol. 2006;97:167–172.
    1. Vergès B, Zeller M, Desgrès J, Dentan G, Laurent Y, Janin‐Manificat L, L'Huillier I, Rioufol G, Beer J‐C, Makki H, Rochette L, Gambert P, Cottin Y. High plasma N‐terminal pro‐brain natriuretic peptide level found in diabetic patients after myocardial infarction is associated with an increased risk of in‐hospital mortality and cardiogenic shock. Eur Heart J. 2005;26:1734–1741.
    1. Vardeny O, Miller R, Solomon SD. Combined neprilysin and renin‐angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663–670.
    1. Vickery S, Price CP, John RI, Abbas NA, Webb MC, Kempson ME, Lamb EJ. B‐type natriuretic peptide (BNP) and amino‐terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy. Am J Kidney Dis. 2005;46:610–620.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner