N-Terminal Pro-B-Type Natriuretic Peptide and Inducible Ischemia in the Heart and Soul Study

Background: B-type natriuretic peptide (BNP) is predictive of inducible ischemia inpatients with coronary heart disease (CHD). Whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a comparable strength of association with ischemia is uncertain. Hypothesis: Resting NT-proBNP levels are associated with inducible ischemia in patients with stable CHD. Methods: We performed a cross-sectional study of 901 outpatients with stable CHD. NT-proBNP was measured in all patients prior to exercise treadmill testing and stress echocardiography. In addition, plasma BNP was measured in a subset Of 355 participants. Logistic regression was used to examine the association of NT-proBNP and BNP quartiles with inducible ischemia. Results: Inducible ischemia was found in 216 (24%) patients. The proportion with inducible ischemia ranged from 42% (95/225) in the highest quartile of NT-proBNP levels (>410 pg/ml) to 9% (21/226) in the lowest quartile (0-72 pg/ml). The highest quartile had a 7-fold greater odds of inducible ischemia than the lowest quartile (odds ratio [OR]: 7.1, 95% confidence interval 101: 4.2-12; P<0.0001). This association remained robust after adjustment for traditional cardiovascular risk factors, left ventricular ejection fraction, and diastolic dysfunction (OR: 3.6, 95% Cl: 1.4-9.1; P = 0.009). In the subgroup with measurements of both NT-proBNP and BNP, both natriuretic peptides were predictive of ischemia. The multivariable-adjusted c-statistics for inducible ischemia were 0.71 for NT-proBNP and 0.62 for BNP (entered as continuous variables). Conclusions: Resting NT-proBNP levels are independently associated with inducible ischemia in outpatients with stable CHD. Baseline elevations of natriuretic peptide may indicate subclinical inducible ischemia in high risk patients with CHD.