Background: Low ADAMTS-13 levels have been repeatedly associated with an increased risk of ischemic stroke, but results concerning the risk of myocardial infarction are inconclusive. Objectives: To perform an individual patient data meta-analysis from observational studies investigating the association between ADAMTS-13 levels and myocardial infarction. Methods: A one-step meta-analytic approach with random treatment effects was used to estimate pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for confounding. Analyses were based on dichotomous exposures, with the 5th and 1st percentiles of ADAMTS-13 antigen levels as cut-off values. Quartile analyses, with the highest quartile as a reference category, were used to assess a graded association between levels and risk ('dose' relationship). Additionally, we assessed the risk of the combined presence of low ADAMTS-13 and high von Willebrand factor (VWF) levels. Results: Five studies were included, yielding individual data on 1501 cases and 2258 controls (mean age of 49 years). Low ADAMTS-13 levels were associated with myocardial infarction risk, with an OR of 1.89 (95% CI 1.15-3.12) for values below the 5th percentile versus above, and an OR of 4.21 (95% CI 1.73-10.21) for values below the 1st percentile versus above. Risk appeared to be restricted to these extreme levels, as there was no graded association between ADAMTS-13 levels and myocardial infarction risk over quartiles. Finally, there was only a minor synergistic effect for the combination of low ADAMTS-13 and high VWF levels. Conclusions: Low ADAMTS-13 levels are associated with an increased risk of myocardial infarction.

ADAMTS13 protein, human, Blood coagulation, Meta-analysis, Myocardial infarction, Risk factors, Von Willebrand factor
dx.doi.org/10.1111/jth.13032, hdl.handle.net/1765/82290
Journal of Thrombosis and Haemostasis
Department of Hematology

Maino, A, Siegerink, B, Lotta, L.A, Crawley, J.T.B, le Cessie, S, Leebeek, F.W.G, … Rosendaal, F.R. (2015). Plasma ADAMTS-13 levels and the risk of myocardial infarction: An individual patient data meta-analysis. Journal of Thrombosis and Haemostasis, 13(8), 1396–1404. doi:10.1111/jth.13032