Background It is unclear whether coronary artery stenosis affects the secretion of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) from the heart independent of ventricular dysfunction. Therefore, this study evaluated the relationship between BNP and NT-proBNP secretion, plasma levels and the severity of coronary artery stenosis in patients with stable coronary artery disease (CAD). Methods and Results Plasma levels of BNP and NT-proBNP in the aortic root (AO) and coronary sinus (CS) in 251 consecutive patients with stable CAD were measured. The transcardiac increase of NT-proBNP was significantly increased with the severity of coronary artery stenosis (p=0.012), but that of BNP was not (p=0.116). The molar ratio of the (CS-AO) NT-pro-BNP/(CS-AO) BNP increased with the severity of coronary artery stenosis (p=0.019) and decreased after coronary revascularization (p=0.018, n=36). Step-wise multivariate linear regression analyses were used to detect independent predictors of the (CS-AO) NT-proBNP among 10 variables including hemodynamic parameters and the Gensini score, which is a measure of the extent and severity of CAD. Among these variables, left ventricular ejection fraction (p<0.0001), left ventricular end-diastolic pressure (p=0.003) and log Gensini score (p=0.008) were significant independent predictors. Conclusion These findings suggest that the transcardiac increase of NT-proBNP from the heart increases with the severity of coronary artery stenosis independent of hemodynamic overload, and plasma NT-proBNP may be superior to BNP to assess disease severity in CAD patients. (Circ J 2007; 71: 499 - 505)