The interplay between VWF, ADAMTS13 and TSP1, and their relation to clinical endpoints

Abstract Introduction ADAMTS13 cleaves von Willebrand Factor (VWF) into less active fragments. TSP1 binds to VWFs cleavage-site, protecting it from degradation. Low ADAMTS13 and high VWF have been associated with cardiovascular disease (CVD) and atrial fibrillation (AF). We aimed to investigate the interplay between VWF, ADAMTS13 and TSP1, and assess any relation to endpoints. Materials and methods 1027 elderly with a recent myocardial infarction (MI) were followed for 2 years. ADAMTS13 antigen (ag) and activity (act), VWF ag and TSP1 were analyzed. The primary endpoint (MACE; n = 210) included MI, stroke, heart failure hospitalization, coronary revascularization and death. The secondary endpoint was new-onset AF (n = 43). Results ADAMTS13 ag and act were weakly correlated to VWF (r = 0.10, P = 0.002, both). TSP1 did not correlate to ADAMTS13 or VWF. Patients experiencing a MACE had higher VWF and lower ADAMTS13(ag) at baseline (P < 0.012, both), however not significant after adjusting for covariates. The association with MACE was mainly driven by death (n = 40), with an adjusted OR 2.4 (P = 0.008) for VWF Q4 vs. Q1-3 and OR 0.4 (P = 0.012) for ADAMTS13(ag) Q1 vs. Q2-4. VWF was lower (1.25 vs. 1.39 IU/mL, P = 0.008) and VWF/ADAMTS13(ag)-ratio was lower (1.81 vs. 2.05 x10−3, P = 0.009) in patients with new-onset AF, and these associations persisted in adjusted models. Conclusion In elderly patients with a recent MI, levels of VWF, ADAMTS13 and TSP1 did not correlate. ADAMTS13 and VWF associated weakly with MACE, mainly driven by death. Low VWF and VWF/ADAMTS13-ratio were associated with new-onset AF in our population and needs further research.