Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease.

CONTEXT Elevated concentrations of B-type natriuretic peptide (BNP) at presentation in patients with acute coronary syndrome (ACS) are associated with long-term mortality. Few data exist regarding serial assessment of BNP levels during follow-up. OBJECTIVE To determine whether concentrations of BNP at study entry (prior to hospital discharge for ACS) and at outpatient follow-up at 4 months and 12 months are associated with subsequent clinical outcomes. DESIGN, SETTING, AND PATIENTS Prospective observational substudy of 4497 patients with non-ST-elevation or ST-elevation ACS who were enrolled in phase Z of the A to Z trial, which was conducted in 41 countries at 322 acute care hospitals between 1999 and 2003. MAIN OUTCOME MEASURE Death from any cause or new onset of congestive heart failure (CHF) through 2 years. RESULTS Levels of BNP were available in 4266 patients at study entry (prior to hospital discharge), 3618 patients at 4 months, and 2966 patients at 12 months. During follow-up there were 230 deaths and 163 incident cases of CHF. Adjusting for age, sex, index event, renal function, hypertension, prior heart failure, and diabetes, elevated levels of BNP (>80 pg/mL) were associated with subsequent death or new CHF when measured at study entry (111 [21%] vs 246 [7%]; adjusted hazard ratio [HR], 2.5; 95% confidence interval [CI], 2.0-3.3), at 4 months (34 [19%] vs 125 [4%]; adjusted HR, 3.9; 95% CI, 2.6-6.0), and at 12 months (19 [11%] vs 37 [1%]; adjusted HR, 4.7; 95% CI, 2.5-8.9). Patients with newly elevated levels of BNP at 4 months were at increased risk of death or new CHF (10 [15%] vs 105 [3%]); HR, 4.5; 95% CI, 2.3-8.6). Patients with elevated levels of BNP at study entry and with BNP levels lower than 80 pg/mL at 4 months tended to have only modestly increased risk (HR, 1.7; 95% CI, 1.0-2.9) compared with patients with BNP levels lower than 80 pg/mL at both visits. CONCLUSIONS Serial determinations of BNP levels during outpatient follow-up after ACS predict the risk of death or new CHF. Changes in BNP levels over time are associated with long-term clinical outcomes and may provide a basis for enhanced clinical decision making in patients after onset of ACS.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00251576.

[1]  R. Califf,et al.  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 , 2003, Circulation.

[2]  N. Arakawa,et al.  Relationship between plasma level of brain natriuretic peptide and myocardial infarct size. , 1994, Cardiology.

[3]  A. Siegbahn,et al.  N-Terminal Pro-Brain Natriuretic Peptide in Relation to Inflammation, Myocardial Necrosis, and the Effect of an Invasive Strategy in Unstable Coronary Artery Disease , 2004 .

[4]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[5]  K. Nakao,et al.  Increased Plasma Levels of Brain Natriuretic Peptide in Patients With Acute Myocardial Infarction , 1993, Circulation.

[6]  J. Herlitz,et al.  N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Acute Coronary Syndromes , 2002, Circulation.

[7]  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.

[8]  J. Cohn,et al.  Effects of Valsartan on Circulating Brain Natriuretic Peptide and Norepinephrine in Symptomatic Chronic Heart Failure: The Valsartan Heart Failure Trial (Val-HeFT) , 2002, Circulation.

[9]  David A Morrow,et al.  Future of Biomarkers in Acute Coronary Syndromes Moving Toward a Multimarker Strategy , 2003, Circulation.

[10]  B. Lindahl,et al.  N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation. , 2002, Journal of the American College of Cardiology.

[11]  M. Pfeffer,et al.  Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. , 2004, JAMA.

[12]  Alan S Maisel,et al.  Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. , 2002, The New England journal of medicine.

[13]  M. Sabatine,et al.  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. , 2003, Journal of the American College of Cardiology.

[14]  C. Frampton,et al.  Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. , 1998, Circulation.

[15]  J. Mair,et al.  The Impact of Cardiac Natriuretic Peptide Determination on the Diagnosis and Management of Heart Failure , 2001, Clinical chemistry and laboratory medicine.

[16]  David A Morrow,et al.  BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. , 2004, Congestive heart failure.

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

[18]  E. Antman,et al.  B-type natriuretic peptide at presentation and prognosis in patients with ST-segment elevation myocardial infarction: an ENTIRE-TIMI-23 substudy. , 2004, Journal of the American College of Cardiology.

[19]  L. Wallentin,et al.  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. , 2005, Journal of the American College of Cardiology.

[20]  H. White,et al.  N-Terminal Pro–B-Type Natriuretic Peptide Levels for Dynamic Risk Stratification of Patients With Acute Coronary Syndromes , 2004, Circulation.

[21]  R. Califf,et al.  The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy. , 2001, American heart journal.

[22]  M. Sabatine,et al.  The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. , 2001, The New England journal of medicine.

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

[24]  E. Antman,et al.  Prognostic value of N-terminal pro-atrial and pro-brain natriuretic peptide in patients with acute coronary syndromes. , 2002, The American journal of cardiology.

[25]  Kukin Ml The Heart Outcomes Prevention Evaluation Study. , 2001, Current cardiology reports.

[26]  J. Herlitz,et al.  N-Terminal ProB – Type Natriuretic Peptide and Long-Term Mortality in Acute Coronary Syndromes , 2002 .

[27]  M. Sabatine,et al.  Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia. , 2004, Journal of the American College of Cardiology.

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

[29]  M. Drazner,et al.  B-type natriuretic peptide in cardiovascular disease , 2003, The Lancet.

[30]  L. Wallentin,et al.  Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure: a multisite study. , 2004, Clinical chemistry.

[31]  D. Barnett,et al.  Profile of plasma N-terminal proBNP following acute myocardial infarction; correlation with left ventricular systolic dysfunction. , 2000, European heart journal.