Attenuation of biologic compensatory action of cardiac natriuretic peptide system with aging

Although plasma B-type natriuretic peptide (BNP) levels increase with age, the mechanisms responsible for this increase are unknown. We investigated the predictors of elevated BNP in older subjects without cardiac systolic dysfunction and overt renal dysfunction. Furthermore, we analyzed the relations between BNP and its second messenger, cyclic guanosine monophosphate (cGMP), to aging. In 252 subjects (mean age 69 +/- 12 years) with left ventricular ejection fraction >/=50% and creatinine levels <==1.5 mg/dl, plasma levels of BNP, cGMP, blood urea nitrogen, creatinine, and beta2-microglobulin (an endogenous marker of renal function), estimated glomerular filtration rate, and echocardiographic data were prospectively evaluated. Plasma BNP levels increased with age (r = 0.4, p <0.0001). With use of multivariate analysis, predictors of elevated BNP levels were age, use of beta blockers, and serum beta2-microglobulin levels. The molar ratio of cGMP to BNP significantly decreased with aging (r = 0.55, p <0.0001). Elevated BNP in older subjects with normal cardiac systolic function may be due in part to renal impairment. With aging, biologic compensation of the cardiac natriuretic peptide system may be attenuated.