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

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.

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.

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.

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%.

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