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Introduction: Small vessel disease can be detected on MRI as white matter hyperintensity (WMH), but its pathophysiology remains elusive. We sought to examine the effect of elevated systolic blood pressure (SBP) and SBP variability on WMH progression in the ACCORD-MIND study of patients with type II diabetes, a prototypical small vessel disease.Methods: MRIs were acquired at baseline and 40 months after enrollment. WMH volume (WMHv) was segmented using an automated volumetric algorithm. The primary outcome was ΔWMHv in mm3, between the two MRI time points. SBP variability was represented as standard deviation and coefficient of variation. Linear regression models were fitted to ΔWMHv with 10 unit shifts in SBP mean and variability as the primary predictors.Results: After excluding one patient for missing data, 502 patients had, on average, 17 (SD±7) SBP readings. In linear regression, SBP variability was not associated with ΔWMHv, while SBP mean was positively associated with ΔWMHv (Table 1). Furthermore, there was an increase in mean ΔWMHv per quartile of mean SBP (Figure 1). The same analysis was performed for diastolic blood pressure and mean arterial pressure, without significant findings.Conclusions: In this uniform cohort of patients with type II diabetes, higher SBP mean, but not SBP variability, was associated with WMHv progression. For every 10 mm Hg increase in SBP mean during ACCORD-MIND, there was a 1.4 mm3 increase in ΔWMHv. These data reinforce the role of hypertension in the pathophysiology of cerebral small vessel disease and provide additional rationale for SBP control to prevent chronic microvascular ischemia in diabetic patients.