ADAMTS13 is a Risk Factor for MI, Stroke and Vascular Death in the Oxford Vascular Study.

Abstract

Normal haemostasis requires a balance between ultra-high MW VWF synthesis/release and its degradation by ADAMTS13. Although a severe acquired/inherited deficiency of ADAMTS13 occurs in TTP, as VWF is an established risk factor for arterial thrombotic disease it has been recently hypothesized that intermediate to low levels of ADAMTS13 could also be an important risk indicator. A new rapid ADAMTS13 Technozym® ELISA activity assay (Technoclone, Vienna, Austria) was therefore used to measure ADAMTS13 activity within plasma samples from a cohort of 521 patients within the Oxford Vascular Study (OXVASC). OXVASC is a large population based study of all patients with acute vascular events (TIA, stroke, acute coronary syndromes and acute peripheral vascular events) and includes a substudy of various risk factors (including platelet function, aspirin responsiveness and classical coagulation markers) for thrombosis. The ADAMTS13 normal range was 68.96 – 144.36% (n = 20, mean = 106.7%, 95% CI = 95.8–115.5%). Within 521 OXVASC samples, the mean ADAMTS13 level was found to be significantly lower (p < 0.0001, Mann-Whitney test) at 72.34% (95% CI = 70.33–74.35%). The minimum and maximum values obtained were 29.17% and 201.86% respectively. Although plasma VWF levels were significantly elevated, they were not inversely proportional to ADAMTS13 activity (r = 0.093). Furthermore low ADAMTS13 levels were not significantly associated with aspirin non-responsiveness (p = 0.0759) as defined by the Collagen/Epinephrine cartridge on the PFA-100, although VWF levels were significantly higher in non-responsive patients (p = <0.0001). Increased VWF levels were predictive of the combined outcome of stroke, MI or vascular death (HR per decile increase 1.12, 95% CI 1.06–1.19, p = 0.0002), whereas lower ADAMTS13 levels were associated with increased risk (HR per decile decrease 0.91 95% CI, 0.85–0.97, p = 0.004). In conclusion, low ADAMTS13 activity was not associated with high VWF levels and there was no association with aspirin non-responsiveness in a high shear dependent assay (PFA-100). However, low levels of ADAMTS13 were predictive of recurrent major vascular events. ADAMTS13 may therefore have some potential as a risk factor in patients with arterial disease.