LAUSR

Introduction: Studies have shown that the volume of white matter hyperintensity (WMH) is a risk factor for stroke, but there are scarce data exploring the relationship between WMH progression on serial MRIs and subsequent risk of stroke. Hypothesis: We hypothesize that WMH progression in the ACCORD trial increases the risk of subsequent incident stroke. Methods: The exposure period was from baseline to month 40, during which an MRI was performed at both baseline and month 40. The primary outcome was incident ischemic stroke after the month 40 MRI until study completion. We fit Cox models to the primary outcome and included both the baseline and month 40 WMH volume as covariates, with the hazard ratio for the month 40 WMH volume of primary interest because it represents WMH progression in this model. Results: We included 497 patients, of whom 53.3% were male and the mean (SD) age was 62.7 (5.7) years at enrollment. Mean (SD) follow-up after the month 40 MRI was 5.2 (1.8) years. Incident stroke occurred in 17 (3.4%) patients, in whom 2 were recurrent strokes and 15 were first-ever strokes. WMH progression was associated with subsequent stroke in the Cox model (HR 1.27, 95% CI 1.03-1.57, p=0.024) and remained significant after adjusting for patient age, history of prior stroke, and cigarette smoking (HR 1.33, 95% CI 1.07-1.65, p=0.010). Conclusions: Although this preliminary analysis is underpowered, WMH progression, independent of absolute WMH burden, may be a risk factor for future stroke in diabetic patients. This novel finding could have translational implications - specifically that interventions which reduce the progression of WMH could, in turn, reduce future risk of stroke.