N-Terminal Pro Brain, N-Terminal Pro Atrial Natriuretic Peptides, and Dynamic Cerebral Autoregulation

Background Elevated natriuretic peptides (NP) are associated with adverse cerebrovascular conditions including stroke, cerebral small vessel disease, and dementia. However, the mechanisms underlying these associations remain unclear. In this study, we examined the relationship of NT-proBNP (N-terminal pro brain NP) and NT-proANP (N-terminal pro atrial NP) with cerebrovascular function, measured by cerebral autoregulation. Methods and Results We included 154 participants (mean age 56±4 years old) from the CARDIA (Coronary Artery Risk Development in Young Adults) cohort. NT-proBNP and NT-proANP were measured in blood samples from the year 25 examination using electrochemiluminescence Immunoassay and enzyme-linked immunoassay, respectively. Dynamic cerebral autoregulation (dCA) was assessed at the year 30 examination by transcranial Doppler ultrasound, using transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations, where lower phase and higher gain reflect less efficient cerebral autoregulation. We used multivariable linear regression models adjusted for demographics, vascular risk factors, and history of kidney and cardiac diseases. Higher NT-proBNP levels at year 25 were associated with lower phase (β [95% CI]=-5.30 lower degrees of phase [-10.05 to -0.54]) and higher gain (β [95% CI]=0.06 higher cm/s per mm Hg of gain [0.004-0.12]) at year 30. Similarly, higher NT-proANP levels were associated with lower phase (β [95% CI]=-9.08 lower degrees of phase [-16.46 to -1.70]). Conclusions Higher circulating levels of NT-proBNP and NT-proANP are associated with less efficient dCA 5 years later. These findings link circulating NP to cerebral autoregulation and may be one mechanism tying NP to adverse cerebrovascular outcomes.