Methods and Results: This single-center prospective longitudinal observational study included 156 individuals aged 65–75 years with well-controlled hypertension, normal LV contraction, and no history of symptomatic heart failure. WMH was quantified on brain magnetic resonance imaging (MRI). The primary outcome was the rate of WMH volume progression between the baseline and follow-up MRI (∆WMH). Participants were classified into tertiles on the basis of ∆WMH (small, medium, and large ∆WMH). The mean (±SD) age at recruitment was 69.6±2.8 years, and the mean follow-up period was 4.6 years. The ratio of early diastolic mitral inflow velocity to early diastolic septal mitral annulus velocity (septal E/e′) was significantly higher in the large ∆WMH group than in the small and medium ∆WMH groups. On multiple regression analysis, septal E/e′ was significantly positively associated with square-root-transformed ∆WMH (β=0.457, P<0.001).