Inverse Association Between Myocardial B-Type Natriuretic Peptide Release and Functional Capacity in Healthy Humans

Background: B-type natriuretic peptide (BNP) has been found to be inversely related to peak oxygen consumption (peak VO₂) in various patient populations. However, in these studies, circulating plasma BNP, i.e. the net effect of release and elimination, rather than cardiac BNP release has been measured. We assessed the relationship between the transcardiac BNP gradient [ΔBNP_CS-A, i.e. the difference between BNP in coronary sinus (BNP_CS) and arterial (BNP_A) plasma] and peak VO₂ in healthy subjects with a view to better understanding the regulation of cardiac BNP release in humans.

Methods: We studied 10 asymptomatic subjects (age 64±11 years, two females) with preserved left ventricular function (left ventricular ejection fraction 62±5%, averaged early diastolic mitral annular velocity 9±3cm/s) and low BNP (BNP in venous plasma [BNP_V] <100ng/l). Subjects underwent measurement of BNP_A and BNP_CS for the calculation of ΔBNP_CS-A, maximal cardiopulmonary exercise testing, echocardiography and resting and submaximal exercise right heart catheterisation.

Results: The median (range) BNP_V, BNP_A, BNP_CS, and ΔBNP_CS-A were 62 (14, 82), 60 (13, 79), 110 (25, 157), and 44 (1, 103) ng/l. The median peak VO₂ during cardiopulmonary exercise testing was 21.5 (18, 54) ml/min/kg. There was an inverse correlation between higher ΔBNP_CS-A and lower peak VO₂ (r=-0.84; p=0.002) and oxygen pulse (r=-0.64, p=0.049). There was a trend towards an inverse correlation between ΔBNP_CS-A and the exercise arteriovenous oxygen content difference (r=-0.58; p=0.08).

Conclusions: In healthy humans, there is an inverse association between myocardial BNP release and peak VO₂, which may be due to cardiac and non-cardiac mechanisms.