Abstract

BACKGROUND: Midlife hypertension is linked to white matter injury and dementia, partly through cerebral small vessel disease. We examined how age and systolic blood pressure (SBP) affect progression of 2 cerebral small vessel disease markers, white matter hyperintensity volume (WMHv), and peak width of skeletonized mean diffusivity, in the SPRINT (Systolic Blood Pressure Intervention) and ACCORD (Action to Control Cardiovascular Risk in Diabetes) trials. METHODS: We assessed age modification of intensive (&lt;120 mm Hg) versus standard (&lt;140 mm Hg) SBP treatment on peak width of skeletonized mean diffusivity (n=440) and asinh transformed WMHv (n=449) progression using linear mixed models in SPRINT using age as a continuous variable and by age group (≤65, 66-75, and &gt;75 years). We performed similar analyses in ACCORD (n=172) on WMHv progression, continuously and in 2 age groups (≤65, 65-79 years). RESULTS: In SPRINT, the overall interaction between age and SBP on WMHv change was not statistically significant (<i>P</i>=0.18). However, intensive SBP treatment demonstrated a stepwise greater longitudinal WMHv reduction with younger age ≤65 years (-0.19 [95% CI, -0.28 to -0.11]), 66 to 75 years (-0.11 [95% CI, -0.19 to -0.02]), &gt;75 years (-0.06 [95% CI, -0.20 to 0.09]), corresponding to respective reductions of 75%, 34%, and 19%. Intensive treatment produced a similar pattern in peak width of skeletonized mean diffusivity progression, with a significant treatment effect in those ≤65 only (<i>P</i>=0.15 for overall treatment by age interaction). In ACCORD, intensive SBP-lowering was associated with reduced WMHv progression in the younger (≤65) compared with the older age group (<i>P</i>=0.038). CONCLUSIONS: Intensive SBP control may be more effective in reducing white matter injury at younger compared with older ages.