Low Plasma ADAMTS-13 Levels Associated with Greater Risk of Myocardial Infarction

Though previous studies have linked low ADAMTS-13 (also known as von Willebrand factor [vWF]–cleaving protease) levels with an increased risk of arterial thrombosis and ischemic stroke, the association with risk of myocardial infarction (MI) has not been defined.

To clarify this relationship, Alberto Maino, from the department of clinical epidemiology at Leiden University Medical Center in the Netherlands, and colleagues conducted a meta-analysis in which they reviewed patient data from five observational studies that reported on the association between ADAMTS-13 levels and incident myocardial infarction. The report was published in the Journal of Thrombosis and Haemostasis.

All of these studies reported on the association between ADAMTS-13 levels and incident myocardial infarction as an acute vascular event, and had a sample size of more than 50 myocardial infarction cases.

The meta-analysis included individual data from a total of 1,501 patients and 2,258 controls. Overall, participants were young, with similar mean ages among the patients and controls (51 years and 47 years, respectively). Cardiovascular risk factors were more prevalent in cases than controls.

In this analysis, plasma ADAMTS-13 levels ≤64 percent were considered low and levels >64 percent were considered high.
“When all of the studies were pooled together, low ADAMTS-13 levels were associated with an almost two-fold increase in the risk of myocardial infarction,” the authors wrote. This association was even stronger when Mr. Maino and colleagues used a more extreme cut-off in an analysis by quartile (TABLE).

“The risk for MI was dramatically higher for patients with ADAMTS-13 values below the first percentile versus above (OR=4.21; 95% CI 1.73-10.21). Multivariable analyses were adjusted for other risk factors for MI, including hypertension, high cholesterol, diabetes, and high body mass index.

The researchers also assessed the risk of myocardial infarction with the combined presence of low ADAMTS-13 levels and high vWF levels, but they found that the risk was “only slightly higher than could be expected by the separate effect, without evidence of a strong interaction.”

The design of the study led to certain limitations, the authors wrote. The case-control design meant that blood was collected after the event in the case groups, which “might lead to reverse causation, or the consequence of an event being mistaken for the cause.”

In addition, several factors could have influenced ADAMTS-13 levels – including the possibility that patients with myocardial infarction had chronic heart failure. ADAMTS-13 deficiency in these patients has been linked to adverse functional outcomes.“

Low ADAMTS-13 levels increased the risk of myocardial infarction,” the authors concluded. “This association is valid only for low ADAMTS-13 levels, and therefore differs from the relationship of ADAMTS-13 with ischemic stroke.”


Reference

Maino A, Siegerink B, Lotta LA, et al. Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis. J Thromb Haemost. 2015;13:1396-1404.

TABLE. Risk of Myocardial Infarction in Relation to Various Plasma Levels of ADAMTS-13

Standardized ADAMTS-13 Levels

Odds Ratio (95% CI)

≤5th percentile (≤64%)

1.75 (0.98–3.12)

1.89 (1.15–3.12)

>5th percentile (>64%)

Reference

Reference

≤1st percentile (≤52%)

4.09 (1.41–11.83)

4.21 (1.73–10.21)

>1st percentile (>52%)

Reference

Reference

Q1 (<83%)

1.38 (0.69–2.78)

1.28 (0.68–2.45)

Q2 (83-97%)

1.23 (0.76–2.01)

1.25 (0.78–1.97)

Q3 (97-112%)

1.12 (0.83–1.52)

1.08 (0.81–1.46)

Q4 (>112%)

Reference

Reference

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