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Background: Myocardial ischemia leads to changes in regional wall stress. Induction of ischemia during a treadmill exercise, although brief, may lead to transient elevation in the plasma level of B-type natriuretic peptide (BNP) from baseline levels, which could serve as a biochemical marker of myocardial ischemia. Methods: Sixty subjects (mean age 57, 41 men) undergoing myocardial single-photon emission computed tomography (SPECT) in conjunction with Bruce protocol treadmill exercise for evaluation of chest pain or screening for ischemia had their BNPs measured (Triage Biosite Test) at baseline, immediately postexercise, and 10 to 15 minutes after exercise. Results: Of the 60 patients, 10 had ischemic perfusion defects by SPECT (mean 14%, range 5%-37%). In patients with no evidence of ischemia, median BNP level at baseline was 15.05 pg/mL (interquartile range 7-37.7), increased significantly immediately postexercise median level (34.7 pg/mL [14.9-67.6]), and decreased toward baseline levels within 10 to 15 minutes postexercise (20.3 pg/mL [8.6-48.5], analysis of variance P < .001). This transient rise in BNP level during exercise was also observed in patients with ischemia but was more pronounced. Percent change in BNP level from baseline for each minute of exercise was significantly higher in patients with evidence of ischemia compared with those without (14% ± SEM 2.3 vs 7% ± SEM 1.2, P = .014). Patients with and without ischemia did not differ in age, exercise time, peak systolic or diastolic blood pressure, peak heart rate, or other baseline characteristics. A >10% change in BNP level from rest per minute of exercise had a sensitivity of 80%, a specificity of 71%, and a negative predictive value of 92% to detect reversible ischemia by SPECT. Conclusion: Transient elevation in BNP occurs during treadmill exercise and is more pronounced in patients with ischemia. B-type natriuretic peptides may therefore be used in combination with treadmill exercise for the evaluation of coronary artery disease. [Copyright &y& Elsevier]