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Study identifies potential new marker
for heart failure diagnosis, prognosis
Measuring several blood proteins
may provide more complete data, allow targeted therapies
BOSTON - September 15, 2006 - A collaborative study by researchers
from Massachusetts General Hospital (MGH) and the University Hospital
of Maastricht, The Netherlands, has identified a new candidate biomarker
for heart failure with the potential of further improving the challenging
task of diagnosing and predicting outcomes for patients with symptoms
of heart failure, primarily shortness of breath. In the September
19 Journal of the American College of Cardiology, the investigators
report that elevated blood levels of galectin-3, an inflammatory
protein, can help diagnose heart failure and identify patients at
risk of dying within 60 days. Another potential marker, apelin,
did not prove to be useful.
"Heart failure is one of the most difficult diagnoses to make
accurately, since it has numerous, varied symptoms, and signs that
indicate heart failure are hard to detect," says James Januzzi
Jr., MD, of the MGH
Cardiology Division, the paper's co-lead author and principal
investigator of the 2005 PRIDE
Study, from which the data for the current report was generated.
"It also is notoriously difficult to identify those heart failure
patients at the highest risk of death, so biomarker screening to
assist with prognostication has been studied and increasingly implemented
over the past several years."
Januzzi and his collaborators have published several studies showing
that testing for a protein called NT-proBNP can aid the diagnosis
of heart failure in patients coming to hospital emergency rooms
with shortness of breath and can identify those at increased risk
of dying within the coming year. Since many biological factors and
processes lead to heart failure, the researchers recognized that
testing for several complementary biomarkers would probably give
the best and most complete information for individual patients.
In addition to NT-proBNP, which is an indicator of stress in the
heart muscle, they also screened for levels of galectin-3, produced
by cardiac inflammatory cells, and apelin, a protein thought to
play a role in heart muscle contraction that was suggested to be
useful for diagnosis and prognosis in heart failure patients. The
investigators tested blood samples gathered in the PRIDE study -
which measured NT-proBNP levels in almost 600 patients who came
to the MGH Emergency Department with shortness of breath - for levels
of the two proteins. Measurements of the potential new markers were
correlated with the detailed PRIDE study follow-up information to
search for associations between protein levels and patient outcomes.
Elevated NT-proBNP levels were the strongest indicator of heart
failure in the study population, but galectin-3 levels also were
markedly increased in a significant proportion of those with heart
failure. In addition, galectin-3 was the most powerful marker of
the short-term risk for death. Importantly, the researchers showed
that the highest risk of short-term death or recurrence of heart
failure symptoms was seen in patients with elevations in both NT-proBNP
and galectin-3. Contrary to prior findings, however, apelin did
not prove useful for either diagnosis or prognosis, a finding that,
Januzzi notes, "may lead investigators away from this marker
for future use in heart failure diagnosis and prognosis."
"The strong predictive power of galectin-3 underscores the
fact that heart failure is also an inflammatory process," explains
Roland van Kimmenade, MD, of University Hospital of Maastricht,
the paper's co-lead author. "Cardiologists tend to forget that
the heart is more than a hollow muscle and that only one third of
the organ consists of muscle cells. Moreover, verifying the role
of galectin-3 in heart failure may lead to new standards for therapeutic
decision making or even the development of new agents that would
inhibit this inflammatory cascade."
Januzzi agrees, "This is the first time a marker with putative
inflammatory function has been shows to have potential diagnostic
and especially prognostic value in heart failure, and the complementary
nature of galectin with NT-proBNP for prognosis is an exciting finding."
He adds, "We are going to be using the PRIDE study data to
examine several other candidate markers that could lead to development
of a comprehensive biomarker profile to guide targeted application
of specific therapies." Januzzi is an assistant professor of
Medicine at Harvard Medical School.
Additional co-authors of the report are Patrick Ellinor, MD, PhD,
Adrian Low, MB, Abelardo Martinez, MD, and Calum MacRae, MB, ChB,
PhD, of MGH Cardiology; and Umesh Shara, MD, PhD, Jaap Bakker, Harry
Crijns, MD, PhD, Paul Menheere, PhD, and Yigal Pinto, MD, PhD, of
University Hospital of Maastricht. The study was supported by grants
from the Netherlands Heart Foundation and the William Marquard Fund
for Cardiac Research. Several of the researchers receive support
from Roche Diagnostics, which manufactures the NT-proBNP assay;
and Pinto holds a patent on cardiovascular applications of galectin-3
testing.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
System, a Boston-based integrated health care delivery system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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