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Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis
A Maino1,2, B Siegerink1,3,4, L A Lotta2
1Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
Insights
Low levels of ADAMTS-13 enzyme are linked to a higher risk of myocardial infarction (heart attack). This meta-analysis confirms the association, particularly with very low enzyme levels.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Biochemistry
Background:
- Low ADAMTS-13 levels are associated with ischemic stroke risk.
- The association between ADAMTS-13 and myocardial infarction (MI) risk is unclear.
Purpose of the Study:
- To conduct an individual patient data meta-analysis on ADAMTS-13 levels and MI risk.
- To investigate the association between ADAMTS-13 enzyme levels and myocardial infarction.
Main Methods:
- Individual patient data meta-analysis of 5 observational studies.
- Pooled odds ratios (ORs) calculated using random-effects model.
- Defined low ADAMTS-13 by 5th and 1st percentiles; assessed quartile associations and combined low ADAMTS-13 with high von Willebrand factor (VWF).
Main Results:
- 1501 cases and 2258 controls analyzed.
- Low ADAMTS-13 levels significantly associated with MI risk (OR 1.89 for <5th percentile, OR 4.21 for <1st percentile).
- No graded association observed across quartiles; minor synergistic effect with high VWF.
Conclusions:
- Low ADAMTS-13 levels are associated with an increased risk of myocardial infarction.
- The risk is most pronounced at extremely low levels of ADAMTS-13.
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.
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