P cute Changes in Circulating Natriuretic eptide Levels in Relation to Myocardial Ischemia arc

OBJECTIVES The aim of this study was to determine the effect of transient myocardial ischemia on circulating natriuretic peptide levels. BACKGROUND Natriuretic peptides are released by the heart in response to wall stress. We hypothesized that transient myocardial ischemia would cause acute changes in circulating natriuretic peptide levels. METHODS B-type natriuretic peptide (BNP), N-terminal fragment of BNP pro-hormone (NT-proBNP), and N-terminal fragment of atrial natriuretic peptide pro-hormone (NT-pro-ANP) levels were measured in 112 patients before, immediately after, and 4 h after exercise testing with nuclear perfusion imaging. RESULTS Baseline levels of BNP were associated with the subsequent severity of provoked ischemia, with median levels of 43, 62, and 101 pg/ml in patients with none, mild-to-moderate, and severe inducible ischemia, respectively (p 0.03). Immediately after exercise, the median increase in BNP was 14.2 pg/ml in patients with mild-to-moderate ischemia (p 0.0005) and 23.7 pg/ml in those with severe ischemia (p 0.017). In contrast, BNP levels only rose by 2.3 pg/ml in those who did not develop ischemia (p 0.31). A similar relationship was seen between baseline NT-pro-BNP levels and inducible ischemia, but the changes in response to ischemia were less pronounced. NT-pro-ANP levels rose with exercise in both ischemic and non-ischemic patients. When added to traditional clinical predictors of ischemia, a post-stress test BNP 80 pg/ml remained a strong and independent predictor of inducible myocardial ischemia (odds ratio 3.0, p 0.025). CONCLUSIONS Transient myocardial ischemia was associated with an immediate rise in circulating BNP levels, and the magnitude of rise was proportional to the severity of ischemia. These findings demonstrate an important link between the severity of an acute ischemic insult and the circulating levels of BNP. (J Am Coll Cardiol 2004;44:1988–95) © 2004 by the American ublished by Elsevier Inc. doi:10.1016/j.jacc.2004.07.057

[1]  D. Muthu,et al.  Rapid Measurement of B-Type Natriuretic Peptide in the Emergency Diagnosis of Heart Failure , 2009 .

[2]  F. Zannad,et al.  Exercise release of cardiac natriuretic peptides is markedly enhanced when patients with coronary artery disease are treated medically by beta-blockers. , 2004, Journal of the American College of Cardiology.

[3]  K. Bibbins-Domingo,et al.  B-Type Natriuretic Peptide and Ischemia in Patients With Stable Coronary Disease: Data From the Heart and Soul Study , 2003, Circulation.

[4]  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.

[5]  Nader Rifai,et al.  Multimarker Approach to Risk Stratification in Non-ST Elevation Acute Coronary Syndromes: Simultaneous Assessment of Troponin I, C-Reactive Protein, and B-Type Natriuretic Peptide , 2002, Circulation.

[6]  D. Morrow,et al.  The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes☆ , 2002 .

[7]  K. Nakao,et al.  Plasma levels of A- and B-type natriuretic peptides in patients with hypertrophic cardiomyopathy or idiopathic dilated cardiomyopathy. , 2000, The American journal of cardiology.

[8]  M. Ohyanagi,et al.  Transient increase in plasma brain (b‐type) natriuretic peptide after percutaneous transluminal coronary angioplasty , 2000, Clinical cardiology.

[9]  J. Wijbenga,et al.  Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice. , 1999, European heart journal.

[10]  D. Gardner,et al.  N ATRIURETIC P EPTIDES , 1998 .

[11]  H. Itoh,et al.  Plasma levels of brain and atrial natriuretic peptides elevate in proportion to left ventricular end-systolic wall stress in patients with aortic stenosis. , 1997, American heart journal.

[12]  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.

[13]  M. Hamada,et al.  Increased secretion of atrial and brain natriuretic peptides during acute myocardial ischaemia induced by dynamic exercise in patients with angina pectoris. , 1995, Clinical science.

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

[15]  N. Minamino,et al.  Isolation and identification of human brain natriuretic peptides in cardiac atrium. , 1990, Biochemical and biophysical research communications.

[16]  K. Nakao,et al.  Atrial pacing stimulates secretion of atrial natriuretic polypeptide without elevation of atrial pressure in awake dogs with experimental complete atrioventricular block. , 1990, Circulation research.

[17]  J. Sundsfjord,et al.  Identification and plasma concentrations of the N-terminal fragment of proatrial natriuretic factor in man. , 1988, The Journal of clinical endocrinology and metabolism.

[18]  A. R. Jonckheere,et al.  A DISTRIBUTION-FREE k-SAMPLE TEST AGAINST ORDERED ALTERNATIVES , 1954 .