von Willebrand factor, ADAMTS-13, and thrombospondin 1 in relation to clinical outcomes in elderly patients with a recent myocardial infarction

Ellen M K Warlo; Are A Kalstad; Peder L Myhre; Svein Solheim; Harald Arnesen; Arnljot Tveit; Pål Andre Holme; Ingebjørg Seljeflot; Vibeke Bratseth

doi:10.1016/j.rpth.2023.100164

von Willebrand factor, ADAMTS-13, and thrombospondin 1 in relation to clinical outcomes in elderly patients with a recent myocardial infarction

Res Pract Thromb Haemost. 2023 Apr 23;7(4):100164. doi: 10.1016/j.rpth.2023.100164. eCollection 2023 May.

Authors

Ellen M K Warlo^{1

2}, Are A Kalstad¹, Peder L Myhre^{2

3}, Svein Solheim¹, Harald Arnesen^{1

2}, Arnljot Tveit^{2

4}, Pål Andre Holme^{2

5}, Ingebjørg Seljeflot^{1

2}, Vibeke Bratseth¹

Affiliations

¹ Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway.
² Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Cardiology, Akershus University Hospital, Lørenskog, Norway.
⁴ Department of Medical Research, Vestre Viken Hospital Trust, Bærum Hospital, Gjettum, Norway.
⁵ Department of Haematology, Oslo University Hospital, Oslo, Norway.

Abstract

Background: von Willebrand factor (VWF) multimers are cleaved by A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) into less active fragments. Thrombospondin 1 (TSP-1) competes with VWF's cleavage site, protecting it from degradation. Low ADAMTS-13 and high VWF have been associated with cardiovascular disease and atrial fibrillation (AF).

Objectives: We aimed to investigate whether VWF, ADAMTS-13, and TSP-1 are associated with clinical outcome.

Methods: Elderly patients with a recent myocardial infarction (MI) (n = 1027) were followed for 2 years. Blood was collected 2 to 8 weeks after the MI for ADAMTS-13, VWF, and TSP-1 measures. The primary endpoints (major adverse cardiovascular events; n = 210) included the first event of MI, stroke, heart failure hospitalization, coronary revascularization, and all-cause death. Total mortality was also registered (n = 56). The secondary endpoint was new-onset AF (n = 43).

Results: Concentrations of VWF, ADAMTS-13, and TSP-1 did not intercorrelate. The risk of major adverse cardiovascular events was altered in patients with VWF ≥ median (hazard ratio [HR], 1.4; 95% CI, 1.0-1.8; P = .03) and ADAMTS-13 ≥ median (HR, 0.7; 95% CI, 0.5-0.9; P = .02); however, it was not significant in adjusted models. VWF and ADAMTS-13 were significantly associated with total mortality, with a HR of 2.7 (95% CI, 1.6-4.6; P < .001) for VWF (Q4 vs. Q1-Q3) and HR of 0.3 (95% CI, 0.2-0.5; P < .001) for ADAMTS-13 (Q2-4 vs. Q1). The associations persisted in multivariable analysis, but the significance disappeared for VWF after correcting for high-sensitivity C-reactive protein. The risk of new-onset AF was lower in patients with VWF ≥ median (HR, 0.5; 95% CI, 0.3-1.0; P = .04]), and this was still significant after adjustments.

Conclusion: Although low ADAMTS-13 predicted death, the cardiovascular risk associated with VWF and ADAMTS-13 was weaker than previously reported. Low VWF is associated with new-onset AF and needs further research.

Keywords: ADAMTS-13; aged; atrial fibrillation; cardiovascular diseases; thrombospondin 1; von Willebrand factor.