Detection of exercise-induced ischemia by changes in B-type natriuretic peptides

J Am Coll Cardiol. 2004 Nov 16;44(10):1980-7. doi: 10.1016/j.jacc.2004.08.045.


Objectives: The purpose of this study was to examine the effect of exercise-induced ischemia on levels of B-type natriuretic peptide (BNP) and its inactive N-terminal fragment (NT-pro-BNP)and to determine whether measurement of these peptides can improve the diagnostic accuracy of exercise testing.

Background: The ability of exercise testing to detect coronary artery disease (CAD) is limited by modest sensitivity and specificity. B-type natriuretic peptides (NT-pro-BNP and BNP) are released by ventricular myocytes in response to wall stress. We hypothesized that exercise-induced ischemia results in increased wall stress and triggers release of NT-pro-BNP and BNP.

Methods: A total of 74 patients with known CAD, normal left ventricular function, and normal resting levels of NT-pro-BNP and BNP who were referred for exercise testing with radionuclide imaging, and 21 healthy volunteers, were enrolled. Blood was drawn before and after maximal exercise and analyzed for NT-pro-BNP and BNP.

Results: Of the patients with CAD, 40 had ischemia on perfusion images and 34 did not. Median post-exercise increases in NT-pro-BNP and BNP (DeltaNT-pro-BNP and DeltaBNP) were approximately four-fold higher in the ischemic group than in the nonischemic group (DeltaNT-pro-BNP 14.5 vs. 4 pg/ml, p < 0.0001; DeltaBNP 36.5 vs. 7.5 pg/ml, p < 0.0001). In volunteers, median DeltaNT-pro-BNP was almost identical to that of the nonischemic patient group. At equal specificity to the electrocardiogram (ECG) (58.8%), the sensitivities of DeltaNT-pro-BNP and DeltaBNP for detecting ischemia were 90% and 80%, respectively; in contrast, the sensitivity of the exercise ECG was 37.5%.

Conclusions: Measurement of exercise-induced increases in BNPs more than doubles the sensitivity of the exercise test for detecting ischemia with no loss of specificity.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Exercise Test
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / diagnosis*
  • Myocardial Ischemia / diagnostic imaging
  • Natriuretic Peptide, Brain / blood*
  • Nerve Tissue Proteins / blood*
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Protein Precursors / blood*
  • ROC Curve
  • Radionuclide Imaging
  • Sensitivity and Specificity


  • Nerve Tissue Proteins
  • Peptide Fragments
  • Protein Precursors
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain