Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis
File(s)Submission_JTH final.pdf (604.02 KB)
Accepted version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2015-07-27
Date Acceptance
2015-05-20
Citation
Journal of Thrombosis and Haemostasis, 2015, 13 (8), pp.1396-1404
ISSN
1538-7933
Publisher
Wiley
Start Page
1396
End Page
1404
Journal / Book Title
Journal of Thrombosis and Haemostasis
Volume
13
Issue
8
Copyright Statement
This is the peer reviewed version of the following article: Maino A, Siegerink B, Lotta LA, Crawley JTB, le Cessie S, Leebeek FWG, Lane DA, Lowe GDO, Peyvandi F, Rosendaal FR. Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis. J Thromb Haemost 2015; 13: 1396–404., which has been published in final form at https://dx.doi.org/10.1111/jth.13032. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Subjects
Science & Technology
Life Sciences & Biomedicine
Hematology
Peripheral Vascular Disease
Cardiovascular System & Cardiology
ADAMTS13 protein
human
blood coagulation
meta-analysis
myocardial infarction
risk factors
von Willebrand factor
VON-WILLEBRAND-FACTOR
THROMBOTIC THROMBOCYTOPENIC PURPURA
CLEAVING PROTEASE ADAMTS13
ISCHEMIC-STROKE
YOUNG-WOMEN
GENE
INCREASE
DISEASE
VWF
DEFICIENCY
Publication Status
Published