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J Thromb Haemost. 2015 Aug;13(8):1396-404. doi: 10.1111/jth.13032. Epub 2015 Jul 14.

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

Author information

1
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
2
A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
3
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
4
Center for Stroke Research, Charité-Universitätsmedizin, Berlin, Germany.
5
Centre for Haematology, Faculty of Medicine, Imperial College London, London, UK.
6
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
7
Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
8
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
9
Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.

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.

KEYWORDS:

ADAMTS13 protein, human; blood coagulation; meta-analysis; myocardial infarction; risk factors; von Willebrand factor

PMID:
26073931
DOI:
10.1111/jth.13032
[Indexed for MEDLINE]
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