Coronary artery disease
Relation of N-Terminal Pro B-Type Natriuretic Peptide Levels After Symptom-Limited Exercise to Baseline and Ischemia Levels

https://doi.org/10.1016/j.amjcard.2008.11.006Get rights and content

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise.

Section snippets

Methods

One hundred one consecutive patients referred for evaluation of the presence or absence of inducible myocardial ischemia and able to perform a bicycle exercise test and subsequent 6-hour blood sampling were included. Patients underwent symptom-limited exercise myocardial perfusion scintigraphy according to a 2-day stress/rest protocol using technetium-99m–tetrofosmin and electrocardiogram (ECG)-gated single-photon emission computed tomography. Blood samples for analysis of NT-proBNP were

Results

Clinical and biochemical characteristics of patients according to the presence or absence of ischemia are listed in Table 1. Patients with ischemia (SDS ≥3; n = 37; 37%) more often were men and more often had a history of coronary artery disease and myocardial infarction and a positive exercise ECG. Baseline NT-proBNP was higher in patients with ischemia (median 184 pg/ml, interquartile range 57 to 386 vs 74, interquartile range 21 to 255 in patients without ischemia, p = 0.043). Table 2 lists

Discussion

Our study showed that after exercise, there was both an immediate and a secondary increase in circulating NT-proBNP. In a multivariate model for the prediction of either an immediate or secondary increase, the presence of myocardial ischemia on the perfusion scan did not add predictive information. Conversely, baseline NT-proBNP in multivariate analysis improved the model significantly. Baseline NT-proBNP was also associated with end-systolic volume and creatinine clearance in multivariate

Acknowledgment

We thank A.H. Zwinderman for statistical assistance and C. Behrens, MD, for assistance in blood sampling and handling.

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