Low ADAMTS‐13 activity and the risk of coronary heart disease – a prospective cohort study: the Rotterdam Study

Abstract

Background The metalloprotease ADAMTS-13 cleaves high-molecular-weight von Willebrand factor multimers into smaller, less procoagulant forms. Low ADAMTS-13 activity is associated with an increased risk of ischemic stroke but its pathogenic role in coronary heart disease (CHD) is unclear. Objectives We aimed to determine the association between ADAMTS-13 activity and the risk of CHD in a large prospective population-based cohort study. Methods A total of 5688 participants of the Rotterdam Study, a population-based cohort study involving individuals aged ≥ 55 years without a history of CHD, were included. ADAMTS-13 activity was measured by the FRETS-VWF73 assay and VWF:Ag levels by ELISA. We assessed the association between ADAMTS-13 activity, VWF:Ag levels and CHD using Cox proportional hazard regression analysis, adjusting for cardiovascular risk factors. Results Over a median follow-up time of 9.7 years, 456 individuals suffered from CHD. A low ADAMTS-13 activity (quartile 1) was associated with an increased CHD risk (HR 1.42, 95% CI 1.07-1.89) compared with the reference highest quartile. Conclusions Low ADAMTS-13 activity is associated with an increased risk of CHD in the elderly, independently of VWF and established cardiovascular risk factors.

Platelets and von Willebrand factor in atherogenesis

“…79 More recently, it was reported that in those without a history of CAD who were followed for approximately a decade, lower levels of plasma ADAMTS13 activity were associated with higher rates of incident coronary events and cardiovascular mortality. 62,63 Activity of ADAMTS13 was more predictive than VWF antigen levels, thereby reinforcing the idea that examination of plasma VWF concentrations may not reflect regulatory processes occurring at the blood poolendothelial interface.…”

“…61 Conversely, in large trials in those with atherosclerotic risk factors but without acute coronary syndrome, circulating levels of VWF are only modestly associated with risk for future atherosclerotic events or cardiac mortality. [61][62][63] These data would seem to argue that VWF becomes functionally important only in late atherothrombotic complications. However, circulating levels of VWF do not necessarily reflect events that occur at the blood pool-endothelial interface or the relative proportion of VWF in ultralarge multimers.…”

Markers of Endothelial Dysfunction: E-selectin, Endothelin-1 and von Willebrand Factor in Patients with Coronary Heart Disease, Including in Combination with Type 2 Diabetes Mellitus

“…В то же время, по данным исследования M.A.H. Sonneveld и соавт., vWF и ADAMTS-13 представляют собой отдельные независимые факторы риска неблагоприятных исходов ИБС [43]. Необходимо подчеркнуть, что дисбаланс vWF и его ингибитора в условиях воспаления (в т.ч., неспецифического) и метаболических нарушений (СД, метаболический синдром) оказывает прокоагулянтный эффект [44,45].…”

Different strokes for older folks (with TTP)

“…5 Previously, large population-based studies have demonstrated an association between lower ADAMTS13 activity with myocardial infarction and stroke. 6,7 Remission ADAMTS13 activity after recovery from acute iTTP is an attractive candidate as a biomarker and therapeutic target to improve long-term outcomes in all patients with iTTP.…”