Von Willebrand Factor, ADAMTS13, and the Risk of Mortality: The Rotterdam Study

Abstract

Objective: Von Willebrand Factor (VWF) is a plasma protein that plays a major role in platelet adhesion and aggregation. Large VWF multimers are cleaved into smaller, less coagulant forms by the metalloprotease ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin motif repeats 13). Previous studies have shown that high VWF and low ADAMTS13 levels are associated with cardiovascular disease, but whether these factors are associated with mortality is unclear. Our aim is to establish the association between VWF antigen (VWF:Ag) levels, ADAMTS13 activity, and mortality.

Approach and results: We included 6130 participants of the Rotterdam study, a population-based cohort study among individuals aged ≥55 years. We determined the association between ADAMTS13 activity, VWF:Ag levels, and all-cause and cardiovascular mortality by Cox proportional hazard regression analysis. During a median follow-up time of 11.3 years and a total of 90 635 person years, 1868 of the 6130 individuals died (30.5%), of whom 442 (23.7%) died because of cardiovascular disease. In individuals with low ADAMTS13 activity, the risk of cardiovascular mortality (hazard ratio, 1.46; 95% confidence interval, 1.09-1.96) was higher than that in individuals with high ADAMTS13 activity. The risk of cardiovascular mortality (hazard ratio, 1.29; 95% confidence interval 0.98-1.70) was higher in individuals with the highest VWF:Ag levels than in those with the lowest levels. In individuals with both low ADAMTS13 activity and high VWF:Ag levels, the risk of cardiovascular mortality was even higher (hazard ratio, 1.73 95% confidence interval, 1.28-2.35).

Conclusions: In this large prospective cohort study, ADAMTS13 activity and VWF:Ag levels are both associated with an increased risk of all-cause and cardiovascular mortality.

Keywords: cardiovascular disease; disintegrins; stroke; thrombospondin; von Willebrand Factor.