Von Willebrand Factor and ADAMTS13 in Relation to Atherosclerosis in the General Population: The Rotterdam Study

Higher von Willebrand factor (VWF) levels and lower ADAMTS13 activity are linked to increased risk of atherosclerotic cardiovascular disease, but their association with atherosclerosis burden, a potential underlying mechanism, remains unclear. We investigated associations of these biomarkers with arterial calcification, a surrogate of atherosclerosis, in a general population.

In 2224 Rotterdam Study participants with measured VWF Antigen level (VWF:Ag) and ADAMTS13 activity (in percentage), computed tomography assessed calcification volume in the coronary arteries (CAC), aortic arch (AAC), and extracranial and intracranial carotid arteries (ECAC, ICAC) (mean age 69.5 ± 6.7 years; 51.5% female). Associations of VWF:Ag, ADAMTS13 activity, and their ratio (linear and quartiles) with calcification (linear and quartiles) were evaluated using multivariable linear and proportional odds logistic regression, adjusting for demographic and cardiovascular factors.

Higher ADAMTS13 activity was significantly associated with lower volume of CAC (β [95% CI]: -0.04 [-0.08, -0.01]), AAC (-0.08 [-0.11, -0.03]), and ECAC (-0.05 [-0.09, -0.01]), but not in ICAC. A higher ADAMTS13:VWF ratio showed stronger inverse associations, extending to ICAC, suggesting a potential interplay between ADAMTS13 and VWF (β [95% CI]: CAC: -0.12 [-0.21, -0.02]; AAC: -0.20 [-0.30, -0.10]; ECAC: -0.08 [-0.18, -0.01]; ICAC: -0.11 [-0.21, -0.02]). The effect size of the ratio increased across quartiles at all artery-specific locations, strengthening the observed relationship. Across levels of calcification, associations of the biomarkers remained generally unchanged.

Our findings support the potential relevance of ADAMTS13 activity in arterial calcification and, by extension, atherosclerosis. The observed associations may reflect both its balance with VWF and pathways independent of VWF. Future longitudinal and causal studies should determine whether ADAMTS13 influences the development and progression of arterial calcification through VWF-dependent or VWF-independent pathways, thereby clarifying its biological role and potentially identifying targets for preventive strategies against atherosclerotic vascular disease.