The velocity reflection index (VRI), derived from carotid Doppler waveforms, showed the strongest correlation with chronological age among eight hemodynamic features in 197 participants (r = 0.738, partial r = 0.798 after adjusting for sex and exercise). A Random Forest model using VRI as the top-ranked feature predicted age with a mean absolute error of 6.87 ± 1.26 years and R² of 0.572, with VRI holding the leading importance rank in 85.3% of bootstrap resamples. Exercise habit showed a modest independent association with VRI after age adjustment, though it attenuated after additional sex correction.
VRI captures wave reflection dynamics in arterial flow — a physiological signature of arterial stiffening that accelerates with age and is mechanistically linked to elevated pulse wave velocity, endothelial dysfunction, and cardiovascular risk. Unlike pulse wave velocity measurements that typically require specialized applanation tonometry or dedicated devices, continuous-wave carotid Doppler is comparatively accessible. If validated, VRI could offer a low-cost proxy for vascular biological age in clinical or population screening settings.
However, critical caveats apply. The cohort of 197 is modest, the study is cross-sectional preventing causal inference, and the authors themselves acknowledge the absence of validation against established arterial-stiffness measures like pulse wave velocity. The R² of 0.57 leaves substantial unexplained variance. Crucially, this is a preprint posted on medRxiv and has not yet been peer-reviewed — findings and methodology remain subject to expert scrutiny. Confirmatory work in larger, independent cohorts is essential before VRI can be considered a clinical vascular-aging tool.