Blood Pressure Variability and Plasma Alzheimer’s Disease Biomarkers in the SPRINT Trial

Abstract

Background: Recent observational studies suggest higher blood pressure (BP) variability (BPV) is associated with Alzheimer’s disease (AD) biomarkers amyloid-beta (Aβ) and tau. Less is known about relationships in interventional cohorts with strictly controlled mean BP levels. Objective: Investigate the longitudinal relationship between BPV and change in plasma AD biomarkers under standard versus intensive BP treatment. Methods: In this post hoc analysis of the SPRINT trial, 457 participants (n = 206 in standard group, n = 251 in intensive group) underwent repeated BP measurement between baseline and 12-months follow-up, and venipuncture at baseline and median (IQR) 3.5 (3.0–4.0) years later to determine plasma AD biomarkers total tau and Aβ 1–42:Aβ 1–40 ratio. BPV was calculated as tertiles of variability independent of mean. Linear mixed models investigated the effect of BPV×time on AD biomarker levels. Results: Higher BPV was associated with increased levels of total tau in the standard group (β [95% CI] 1st versus 3rd tertiles of BPV: 0.21 [0.02, 0.41], p = 0.035), but not in the intensive group (β [95% CI] 1st versus 3rd tertiles of BPV: −0.02 [−0.19, 0.16], p = 0.843). BPV was not associated with Aβ 1–42:Aβ 1–40 ratio in either group. Mean BP was not associated with biomarkers. Conclusions: Higher BPV was associated with increased plasma total tau under standard BP treatment. Findings add new evidence to prior observational work linking BPV to AD pathophysiology and suggest that, despite strict control of mean BP, BPV remains a risk for pathophysiological change underlying risk for AD.

Blood Pressure Variability and Plasma Biomarkers of Neuronal Injury and Alzheimer’s Disease: A Clinic-Based Study of Patients with Diseases Along the Heart-Brain Axis

“…Besides, the intensity of blood pressure treatment could be another relevant factor. Among individuals at risk for cardiovascular disease, higher BPV was associated with increased plasma total tau in the standard, but not intensive, blood pressure treatment group [ 30 ]. In our cohort of patients with overt cardiovascular disease, effect modification analyses might have revealed significant associations, although all patients were treated similarly according to current guidelines and differences between treatment groups would have likely been small.…”