Association of Augmentation Index With Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.

Background: Augmentation index (Aix) is a widely used index of pressure wave reflections (PWRs) derived from noninvasive blood pressure waves recordings and pulse wave analysis. Cerebral small vessel disease (cSVD) comprises various pathological processes affecting the brain's microvasculature and is a major cause of vascular cognitive impairment, ischemic, and hemorrhagic stroke. This meta-analysis aimed to assess the association between PWRs, as measured by AIx, and cSVD as identified through neuroimaging biomarkers, and to explore potential differences based on arterial site of AIx measurement.

Methods: Following a predefined protocol adhering to the Meta-Analysis of Observational Studies in Epidemiology guidelines, nine studies comprising a total of 6,774 participants were included. Pooled effect estimates were calculated to evaluate the relationship between AIx and cSVD markers, including white matter hyperintensities (WMH).

Results: A marginal positive association was observed between AIx and cSVD [central (carotid and aortic) AIx: β=0.04 (95% CI: 0.01-0.07) per SD increase; carotid AIx: β=0.05 (95% CI: 0.00-0.09); aortic AIx: β=0.03 (95% CI: 0.00-0.06)]. Similar results were found for the association between AIx and WMH [central (carotid and aortic) AIx: β=0.05 (95% CI: 0.01-0.08); carotid AIx: β=0.05 (95% CI: 0.00-0.10); aortic AIx: β=0.05 (95% CI: 0.00-0.010)].

Conclusions: AIx showed a marginal positive association with cSVD, but the clinical relevance remains unclear. Substantial heterogeneity across studies, along with the absence of data on other PWR indices, limits the robustness and generalizability of these findings. Future research should employ advanced methodologies capable of assessing local PWR coefficients to better elucidate the relationship between PWRs and brain microcirculation.