Estimated pulse wave velocity, dementia risk, and vascular aging phenotypes: a post-hoc analysis of the SPRINT-MIND trial in the United States

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Abstract
Background: Vascular aging contributes to dementia risk, yet clinically interpretable markers for risk stratification remain limited. Estimated pulse wave velocity (ePWV), derived from age and mean arterial pressure, provides an accessible surrogate of arterial stiffness. We evaluated whether baseline ePWV identifies an interpretable threshold for probable dementia and distinct vascular aging phenotypes.Methods: We conducted a post-hoc analysis of SPRINT-MIND including 8,536 participants free of dementia at baseline. Baseline ePWV was calculated using age and mean arterial pressure. The primary outcome was incident probable dementia adjudicated during follow-up. Associations between ePWV and dementia risk were assessed using spline-based and quartile-based Cox proportional hazards models. Model discrimination was evaluated using Harrell’s C-index.Results: During follow-up, 323 participants developed probable dementia. Dementia risk was lowest at lower ePWV values and increased beyond approximately 10.7 m/s, identifying an interpretable risk threshold. Risk was concentrated in the highest ePWV quartile, consistent with a threshold-like pattern rather than a uniform linear gradient. In exploratory analyses, longitudinal clustering identified distinct ePWV trajectory phenotypes over 24 months.Conclusions: Baseline ePWV identified an interpretable dementia risk threshold and distinct vascular aging phenotypes in SPRINT-MIND. These findings support ePWV as a clinically interpretable marker of vascular aging that may aid dementia risk stratification.
Funding Information
  • National Institutes of Health

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