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Protein Released by Dying Heart Muscle During Heart Attacks Identifies High-Risk Patients, Predicts Long-Term Risk

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Duke Health News 919-660-1306

ORLANDO, FL -- Two different multi-hospital studies have
demonstrated that a blood test can indicate which heart attack
patients may be in danger of dying from a heart attack, Duke
University Medical Center researchers reported Monday. The
original version of the test takes one to two hours in a
laboratory for results, while a newer version can identify the
highest-risk patients in as little as 10 minutes. That time
difference can literally mean life or death for these heart
attack patients, said Duke cardiologist Dr. E. Magnus Ohman,
leader of one of the studies.

Both tests measure the presence of "troponin T," a
regulatory protein that helps heart muscle contract. Once this
muscle starts dying, as in a heart attack, cell membranes break
down and internal cellular material, including proteins, are
released and are carried away by the blood.

"Anything that can help us make quick treatment decisions
about patients with myocardial infarctions (heart attacks) is
invaluable," Ohman said. "We studied this test prospectively on
more than 12,000 patients, making this the largest such trial
ever conducted."

Ohman was principal investigator in a study published Oct.
31, 1996 in the New England Journal of Medicine demonstrating
that troponin T was the best indicator yet of which heart
attack patients are at greatest risk of dying of another attack
within 30 days. His new study looked at the rapid test for the
first time.

The rapid version of the test, which is administered at the
patient's bedside, detects only the presence or absence of
troponin T, while the laboratory version indicates how much of
the protein is in the blood, Ohman said.

"Our study indicates convincingly that merely the presence
of troponin T is a strong predictor of further cardiac events
or death," Ohman said in an interview.

Duke cardiologist Dr. Kristin Newby led the second study,
which looked at the patients one year after treatment.

"We knew that a positive troponin T finding is a strong
predictor of 30-day mortality or in patients suffering from
another heart attack," she said. "After following up one year
later with 855 heart attack patients, we found that the test's
ability to predict risk remained the same."

Specifically, after one year, 14.2 percent of the patients
with a positive troponin T finding had died, while only 5.8
percent with a negative troponin T finding died. The earlier
study showed a 10.4 percent vs. 3.3 percent mortality at the
30-day endpoint.

"This test is a powerful diagnostic tool to help us identify
the highest-risk patients," Newby said. "The challenge for
cardiologists is now to determine which of the many therapies
available to us should be used to reduce the future risks for
these patients."

Ohman and Newby prepared the results of their studies for
presentation Monday at the 70th scientific session of the
American Heart Association (AHA).

Ohman's study followed 12,635 patients at 600 hospitals in
the United States and abroad enrolled in the GUSTO-III (Global
Utilization of Strategies to Open Occluded Arteries in Acute
Coronary Syndromes) trial, which compared the benefits of
clot-busters reteplase and alteplase.

Overall, 8.9 percent of the GUSTO-III patients tested
positive for troponin T, and 6.9 percent of them died within 24
hours, compared to 2.1 percent for troponin T-negative
patients, Ohman said. The in-hospital death was 14.4 percent
for troponin t-positive patients and 5.5 percent for the
negative patients.

"Importantly, this test was a potent indicator independent
of other risk factors such as age and location of infarction,"
Ohman said. "Also, the test is very easy to perform."

"We expect that the use of this test will continue to grow
because it is so specific in detecting cardiac troponin T in
the blood," Newby said. "We can detect very low levels of the
protein, which makes it a valuable prognostic tool for
cardiologists."

The AHA estimates that in one year as many as 1.5 million
Americans will have a heart attack and 500,000 of them will
die. Thousands of those who die will have been prematurely
released from the hospital because their heart attack was not
diagnosed, researchers said.

The test can give cardiologists a head start in initiating
immediate heart care, Newby said.

"Most of the negative events that happened to these patients
occurred in the first 30 days," Newby explained. "Between 30
days and one year, the mortality rates were about the same. So
it is important to initiate treatment very early in patients
who have positive troponin T levels.

The cardiologists said that further studies are needed to
determine exactly which of the many treatment options – whether
procedure or drug based – will work the best for troponin
T-positive patients.

Newby and colleagues analyzed data from a sub-study of a
larger clinical trial known as GUSTO IIa. That trial was
supported by Ciba-Geigy Corp., Advanced Cardiovascular Systems,
and the German pharmaceutical company Boehringer Mannheim,
which manufactures the troponin T test.

The trial involved 855 patients in the U.S. and Canada, and
involved physicians from both small community hospitals and
large research centers.

Joining Newby in the study, from Duke, were, Ohman and
Steven Peck; Robert Christenson, University of Maryland; Dr.
Hugo Katus, University of Heidelberg, Germany; Dr. Christian
Hamm, University Hospital Epperdorf, Hamburg, Germany; and Dr.
Paul Armstrong, University of Alberta, Edmonton, Canada.

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