Plasma ADAMTS-13 levels and the risk of myocardial infarction: An individual patient data meta-analysis

A. Maino, B. Siegerink, L. A. Lotta, J. T B Crawley, S. le Cessie, F. W G Leebeek, D. A. Lane, G. D O Lowe, F. Peyvandi, F. R. Rosendaal

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1396-1404
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

Keywords

  • ADAMTS13 protein, human
  • Blood coagulation
  • Meta-analysis
  • Myocardial infarction
  • Risk factors
  • Von Willebrand factor

ASJC Scopus subject areas

  • Hematology

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