CLINICAL NEWS
Literature Scan
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 metaanalysis 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
Risk of Myocardial Infarction in Relation
to Various Plasma Levels of ADAMTS-13
used a more extreme cut-off in an
analysis by quartile (TABLE 2).
“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 2.
Standardized ADAMTS-13
Levels
Odds Ratio (95% CI)
Univariate analyses
Multivariate analyses
≤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)
Reference
Reference
Q4 (>112%)
“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.”
—ALBERTO MAINO
52
ASH Clinical News
Fludarabine + Busulfan:
Improving Treatment-Related
Mortality without Compromising
Conditioning Intensity in High-Risk
Multiple Myeloma
A myeloablative conditioning
regimen consisting of fludarabine
and busulfan was safe and effective
in patients with high-risk multiple
myeloma undergoing allogeneic
hematopoietic cell transplantation (Allo-HCT) and decreased
treatment-related mortality – and
was comparable with conventional
conditioning regimens – according
to a report published in Biology of
Blood and Marrow Transplantation. The fludarabine and busulfan
regimen was also associated with
no instances of early toxic death or
graft failure.
“Despite the ongoing advent of
more effective immunomodulators
and proteasome inhibitors, multiple
myeloma remains incurable and no
effective therapy is available for advanced, aggressive disease,” the au-
thors, led by Attaphol Pawarode,
MD, from the Blood and Marrow
Transplantation Program at the
University of Michigan in Ann
Arbor, Michigan, wrote.
Although Allo-HCT has a
curative potential for these patients,
their clinical outcomes remain poor
due to high treatment-related mortality, mostly related to “regimenrelated toxicities and graft-versushost disease (GVHD) with use of
myeloablative conditionings, high
relapse rate with use of reducedintensity or nonmyeloablative regimens, and possibly other unknown
multiple myeloma–specific issues,”
the authors noted.
In an effort to improve
treatment-related mortality without compromising conditioning
intensity, Dr. Pawarode and inves-
September 2015