title: Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Maino
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.|Center for Stroke Research, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Siegerink
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors.forename: L A
authors.initials: LA
authors.lastname: Lotta
authors.affiliation: Centre for Haematology, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: J T B
authors.initials: JT
authors.lastname: Crawley
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: le Cessie
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: F W G
authors.initials: FW
authors.lastname: Leebeek
authors.affiliation: Centre for Haematology, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Lane
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: G D O
authors.initials: GD
authors.lastname: Lowe
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.|Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D015536:Down-Regulation; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology*; D064887:Observational Studies as Topic; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13 protein, human; blood coagulation; meta-analysis; myocardial infarction; risk factors; von Willebrand factor