Increased VWF-to-ADAMTS13 ratio is associated with large cerebral white matter hyperintensities

ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) cleaves highly prothrombotic high molecular weight multimers of von Willebrand factor (VWF). Elevated VWF and low ADAMTS13 activity are associated with ischemic stroke but the association with cerebral white matter hyperintensities (WMH), which are associated with the risk of stroke and mortality, has never been studied. We investigated whether the ratio of VWF antigen to ADAMTS13 activity (VWF-to-ADAMTS13 ratio) is associated with the presence of any WMH or large WMH (≥3 mm) in the Genetic Study for Atherosclerosis Risk cohort. A total of 287 participants with completed brain magnetic resonance imaging had available samples for measurement of VWF antigen and ADAMTS13 activity. Median (interquartile range [IQR]) VWF-to-ADAMTS13 ratio was higher in those with WMH than in those without WMH (0.623 [IQR, 0.434-0.926] vs 0.509 [IQR, 0.373-0.804]; P = .013). Similarly, the VWF-to-ADAMTS13 ratio was higher in those with large WMH than in those without large WMH (0.702 [95% confidence interval (CI), 0.468-1.083] vs 0.514 [95% CI, 0.373-0.836]; P = .003). In a mixed-effects logistic regression model, the log-transformed VWF-to-ADAMTS13 ratio was significantly associated with large WMH (odds ratio, 1.93 [95% CI, 1.21-3.07]) after adjusting for age and other vascular risk factors and accounting for family structure. In conclusion, the VWF-to-ADAMTS13 ratio is associated with WMH in a cohort at an increased risk of cardiovascular disease and may play a role in the pathogenesis of cerebral small vessel disease and its associated complications including cognitive impairment, stroke, and mortality.