Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction.

BACKGROUND Newly discovered circulating peptides, N-terminal pro-brain natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction. METHODS AND RESULTS The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001) after infarction was comparable to that for C-terminal BNP and far stronger than for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C-terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of death over 24 months of follow-up, an early postinfarction N-BNP level > or = 160 pmol/L had sensitivity, specificity, positive predictive value, and negative predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a patient with an N-BNP level below the group median (Kaplan-Meier survival analysis, P<.00001). For prediction of heart failure (left ventricular failure), plasma N-BNP > or = 145 pmol/L had sensitivity (85%) and negative predictive value (91%) comparable to the other cardiac peptides and was superior to ADM, plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM provided predictive information for death and left ventricular failure independent of patient age, sex, LVEF, levels of other hormones, and previous history of heart failure, myocardial infarction, hypertension, or diabetes. CONCLUSIONS Plasma N-BNP measured 2 to 4 days after myocardial infarction independently predicted left ventricular function and 2-year survival. Stratification of patients into low- and high-risk groups can be facilitated by plasma N-BNP or BNP measurements, and one of these could reasonably be included in the routine clinical workup of patients after myocardial infarction.

[1]  Fach,et al.  Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF) , 1999, The Lancet.

[2]  K. Kangawa,et al.  Plasma adrenomedullin as an indicator of prognosis after acute myocardial infarction , 1999, Heart.

[3]  R. Doughty,et al.  Neurohumoral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. , 1999, Circulation.

[4]  CIBIS-II Investigators and Committees The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial , 1999, The Lancet.

[5]  A. Richards,et al.  Adrenomedullin(1-52) measured in human plasma by radioimmunoassay: plasma concentration, adsorption, and storage. , 1998, Clinical chemistry.

[6]  T. Yoshimoto,et al.  Potentiation of Natriuretic Peptide Action by the β -Adrenergic Blocker Carvedilol in Hypertensive Rats: A New Antihypertensive Mechanism. , 1998, Endocrinology.

[7]  M. Redfield,et al.  Adrenomedullin in experimental congestive heart failure: cardiorenal activation. , 1997, The American journal of physiology.

[8]  G. Cooper,et al.  Beneficial hemodynamic and renal effects of adrenomedullin in an ovine model of heart failure. , 1997, Circulation.

[9]  R. Doughty,et al.  Immunoreactive amino‐terminal pro‐brain natriuretic peptide (NT‐PROBNP): a new marker of cardiac impairment , 1997, Clinical endocrinology.

[10]  G. Cooper,et al.  Hemodynamic, hormonal, and renal effects of adrenomedullin in conscious sheep. , 1997, The American journal of physiology.

[11]  Australia. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease , 1997, The Lancet.

[12]  S. Anker,et al.  Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. , 1997, Circulation.

[13]  K. Bailey,et al.  Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy. , 1996, Hypertension.

[14]  C R Benedict,et al.  Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators. , 1996, Circulation.

[15]  C. Lang,et al.  Diagnostic value of B-type natriuretic peptide concentrations in patients with acute myocardial infarction. , 1996, The American journal of cardiology.

[16]  N. Arakawa,et al.  Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction. , 1996, Journal of the American College of Cardiology.

[17]  R. T. Lie,et al.  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. , 1996, Circulation.

[18]  J. Cohn,et al.  The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. , 1996, The New England journal of medicine.

[19]  R. Rodeheffer,et al.  Cardiac secretion of adrenomedullin in human heart failure. , 1996, The Journal of clinical investigation.

[20]  N. Kennedy,et al.  Comparison of atrial natriuretic peptide B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide as indicators of left ventricular systolic dysfunction. , 1996, The American journal of cardiology.

[21]  G. Maurer,et al.  Prognostic impact of big endothelin-1 plasma concentrations compared with invasive hemodynamic evaluation in severe heart failure. , 1996, Journal of the American College of Cardiology.

[22]  K. Kangawa,et al.  Plasma adrenomedullin concentration in patients with heart failure. , 1996, The Journal of clinical endocrinology and metabolism.

[23]  L. Navar,et al.  Renal responses to intra-arterial administration of adrenomedullin in dogs. , 1996, The American journal of physiology.

[24]  K. Dickstein,et al.  Plasma proatrial natriuretic factor is predictive of clinical status in patients with congestive heart failure. , 1995, The American journal of cardiology.

[25]  A. Richards,et al.  The amino-terminal portion of pro-brain natriuretic peptide (Pro-BNP) circulates in human plasma. , 1995, Biochemical and biophysical research communications.

[26]  N. Minamino,et al.  Effects of vasoactive substances and cAMP related compounds on adrenomedullin production in cultured vascular smooth muscle cells , 1995, FEBS letters.

[27]  J. Burnett,et al.  Elevation of circulating and ventricular adrenomedullin in human congestive heart failure. , 1995, Circulation.

[28]  D. Parkes Cardiovascular actions of adrenomedullin in conscious sheep. , 1995, The American journal of physiology.

[29]  J. Rouleau,et al.  Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of captopril. , 1994, Journal of the American College of Cardiology.

[30]  G. Lamas,et al.  N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction. , 1994, Circulation.

[31]  R. T. Lie,et al.  Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction. , 1994, Circulation.

[32]  K. Kangawa,et al.  Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma , 1994, FEBS letters.

[33]  R. T. Lie,et al.  Prognostic value of plasma atrial natriuretic factor, norepinephrine and epinephrine in acute myocardial infarction. , 1993, The American journal of cardiology.

[34]  G. Lamas,et al.  Activation of neurohumoral systems in postinfarction left ventricular dysfunction. , 1993, Journal of the American College of Cardiology.

[35]  J. Cohn,et al.  Plasma Norepinephrine, Plasma Renin Activity, and Congestive Heart Failure Relations to Survival and the Effects of Therapy in V‐HeFT II , 1993, Circulation.

[36]  K. Bailey,et al.  Circulating N-terminal atrial natriuretic peptide as a marker for symptomless left-ventricular dysfunction , 1993, The Lancet.

[37]  A. Struthers,et al.  Plasma brain natriuretic peptide as an indicator for angiotensin-converting-enzyme inhibition after myocardial infarction , 1993, The Lancet.

[38]  K. Kangawa,et al.  Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. , 1993, Biochemical and biophysical research communications.

[39]  A. Richards,et al.  Assay of brain natriuretic peptide (BNP) in human plasma: evidence for high molecular weight BNP as a major plasma component in heart failure. , 1993, The Journal of clinical endocrinology and metabolism.

[40]  K. Minaker,et al.  Atrial natriuretic peptide levels in the prediction of congestive heart failure risk in frail elderly. , 1992, JAMA.

[41]  S. Yusuf,et al.  Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). , 1990, Circulation.

[42]  K. Swedberg,et al.  Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. , 1990, Circulation.

[43]  H. Fillit,et al.  Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. , 1990, The New England journal of medicine.

[44]  E. Espiner,et al.  Radioimmunoassay and characterization of atrial natriuretic peptide in human plasma. , 1986, The Journal of clinical endocrinology and metabolism.

[45]  J. Cohn,et al.  Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. , 1984, The New England journal of medicine.

[46]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[47]  J. Izzo,et al.  Validity and reliability of liquid chromatography with electrochemical detection for measuring plasma levels of norepinephrine and epinephrine in man. , 1981, Life sciences.

[48]  C W Parker,et al.  Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. , 1972, The Journal of biological chemistry.