Carotid Flow Augmentation, Arterial Aging, and Cerebral White Matter Hyperintensities

Objective- Aortic stiffness and pressure wave reflection are associated with age-related cerebral microvascular disease, but the underlying mechanism remains obscure. We hypothesized that cerebral (carotid) flow alterations potentially mediate these associations. Approach and Results- Doppler waveforms were recorded in 286 patients with hypertension to measure the carotid flow augmentation index (FAIx) as the late/early-systolic velocity amplitude ratio. Tonometric waveforms were recorded to estimate the aortic pressure AIx (PAIx), aortic compliance, and carotid-femoral and carotid-radial pulse wave velocities. Additionally, white matter hyperintensities on brain magnetic resonance imaging were evaluated using the Fazekas scale. With increasing age, the carotid late systolic velocity increased, whereas the early systolic velocity decreased, although the aortic augmented pressure increased in parallel with the incident wave height ( P<0.001). Both FAIx and PAIx increased with age, but the age-dependent curves were upwardly concave and convex, respectively. FAIx increased exponentially with increasing PAIx ( r=0.71). Compared with PAIx, FAIx was more closely ( P≤0.001) correlated with the aortic pulse wave velocity, aortic compliance, and elastic/muscular pulse wave velocity ratio. FAIx was associated with white matter hyperintensities scores independently of confounders including age, sex, diabetes mellitus, hypercholesterolemia, and aortic pulse wave velocity ( P=0.01), and was more predictive of white matter hyperintensities presence than PAIx. Conclusions- Carotid FAIx had closer associations with age, aortic stiffness, and cerebral white matter hyperintensities than aortic PAIx. These results indicate that carotid flow augmentation (enhanced by aortic stiffening and pressure wave reflection from the lower body) causes microcerebrovascular injury potentially through increasing cerebral flow pulsations, but this detrimental effect is greater than that estimated from PAIx.