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DURHAM, NC -- A new brain chemical test that predicts which patients with heart attack symptoms are at higher risk of dying is paradoxically not being used in younger, healthier patients who could benefit the most from the prognostic information provided by this test, according to a new analysis by cardiologists at the Duke Clinical Research Institute (DCRI).

While previous studies have shown that elevated levels of "brain natriuretic peptide" (BNP) in the blood are associated with higher risks of death in heart attack patients, researchers know little about how this new test is actually being used in U.S. hospitals to risk stratify patients with heart attacks.

Natriuretic peptides are produced by the brain and heart tissue where there is hemodynamic stress on the heart as a signal to the kidneys to produce more urine, which in turn reduces the volume of blood fluid, facilitating damaged or weakened heart muscle to pump blood throughout the body. Larger elevations of BNP levels have been previously shown to be associated with an incremental increase in the risk of mortality for heart attack patients.

In their analysis, the researchers found that the BNP test was performed mainly on patients who already had many high-risk clinical factors, such as history of congestive heart failure, older age and diabetes. However, the researchers discovered, younger and seemingly healthier patients with elevated BNP levels were actually at a two to four times greater risk of dying in the hospital than the high-risk patients with elevated BNP levels.

"Among all the patients in our analysis who had BNP levels measured, incremental increases in BNP levels were associated with higher risks of in-hospital death," said DCRI cardiologist Matthew Roe, MD, who presented the results of his analysis March 14, 2006, during the 55th annual scientific sessions of the American College of Cardiology (ACC) in Atlanta.

"However, the mortality risks associated with higher BNP levels were greater among sub-groups of patients who were less likely to have BNP levels measured at all," Roe continued. "It appears that physicians were ordering tests for those patients who would already be considered at the highest risk of early mortality, such as those with congestive heart failure on hospital presentation. More randomized trials are needed to specifically identify those patients who should be tested and those who would benefit the most from this new test."

To understand more clearly how the BNP test is used in the U.S., Roe and his colleagues consulted the national quality improvement initiative known as CRUSADE, which stands for "Can Rapid risk stratification of UnStable Angina patients suppress aDverse outcomes with Early implementation of the ACC/American Heart Association (AHA) guidelines."

CRUSADE continuously gathers data from participating hospitals that treat patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) – including patients with a certain type of heart attack known as non-ST-segment elevation myocardial infarction. These patients come to hospital emergency rooms with heart attack symptoms and are found to have chemical signs of heart muscle death and/or electrocardiogram tests showing areas of ischemia in the heart. About 1.3 million Americans are hospitalized each year with NSTE ACS.

During a 20-month period ending in 2004, 30,324 NSTE ACS patients were treated at 312 CRUSADE hospitals. A total of 19.4 percent of those patients had their BNP levels measured.

'The finding that one in five patients received the test is in line for something as new as this type of laboratory test," Roe. "However, at this point it is not being used in the right patients. It appears that the test is predominantly being ordered in older patients with a history of heart failure or signs of heart failure on presentation. These patients are already at a high risk of early mortality based upon these features alone, so an additional test does not add much in terms of the precision of mortality risk prediction."

Specifically, patients who did not have signs of congestive heart failure in the emergency room but had the highest levels of BNP were more than twice as likely to die in the hospital as heart failure patients with the same high BNP levels. In terms of age, those under the age of 65 with high BNP levels were almost four times as likely to die in the hospital as those over 65 with high BNP levels.

Roe said that the findings of an analysis such as this one should provide the scientific basis for physicians who see NSTE ACS patients in the emergency room to refine their use of the BNP test during the early clinical evaluation of these patients.

"For younger, healthier patients with NSTE ACS, the BNP test might prove more insightful, providing an early indication of a higher risk of mortality in patients who would otherwise be considered to have a relatively low-risk of mortality based upon their younger age and lack of other high-risk clinical features ," Roe continued. "Aggressive treatment or in the early stages of presentation with NSTE ACS in these patients with elevated BNP levels could prove effective in saving lives."

CRUSADE is coordinated by the DCRI, with Roe and Duke cardiologist Eric Peterson, MD, serving as principal investigators. CRUSADE continuously gathers data from more participating U.S. hospitals and provides regular feedback to hospitals with the ultimate goal of improving adherence to the ACC/AHA treatment guidelines and patient outcomes.

CRUSADE is funded by Schering-Plough Corp., Kenilworth, NJ. The Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, NY, provides additional funding support. Millennium Pharmaceuticals, Inc. also funded this research. Roe has received research grants and served on the speaker's bureau of the sponsors.