Protein spots heart patients at high risk for death

American Heart Association
Tuesday, 8 July 2003

A small protein with a long name may become the latest blood biomarker to guide physicians who treat heart attack patients, according to a study in today's rapid access issue of Circulation: Journal of the American Heart Association.

Called N-terminal pro-brain natriuretic peptide, or NT-proBNP, the biomarker is among a group of blood elements being studied for their ability to provide prognostic information after heart attacks. Other such markers include troponin T and C-reactive protein (CRP).

NT-proBNP is a hormone that is released from the heart's lower ventricles in response to increased wall tension. Its levels increase after heart attack. Previous studies have found that the NT-proBNP can predict death among patients with a common type of acute coronary syndrome (ACS).

In this study, researchers evaluated the characteristics of patients with elevated serum NT-pro-BNP and the prognostic information it provided. They found that the higher levels of NT-proBNP were associated with increased risk of death as early as 48 hours after symptom onset and for up to one year later.

"This is crucial information that can help doctors evaluate patients after symptoms begin and stratify patients into low- and high-risk groups," says lead author Stefan K. James, M.D., Ph.D., department of cardiology, Academic Hospital, Uppsala, Sweden.

"Non-ST elevation acute coronary syndrome" is a common name for a heart attack without ST elevation – the specific electrocardiogram changes (ECG) associated with heart attack– and unstable angina, or chest pain that is unpredictable and can occur at rest. Since these patients do not have specific ECG changes after hospital admission and sometimes do not experience other specific symptoms of heart attack, they might be released without receiving much-needed cardiac treatment," James says.

Using blood samples from 6,809 patients (average age 65) admitted to hospitals with chest pain and participating in the multinational Global Utilization of Strategies to Open Occluded Arteries-IV (GUSTO IV) trial, researchers looked for the markers NT-proBNP, troponin T and C-reactive protein (CRP). Troponin is a peptide released as heart cells die. CRP is released from the liver as a response to inflammation. Patients with ACS and increased serum levels of CRP or troponin T have an increased risk of death, James says.

The researchers divided patients into four groups based on their levels of NT-proBNP. Group one had the lowest level and group four had the highest. The difference in death rate was apparent after two days. People in the lowest group of NT-proBNP had a death rate of 0.2 percent (3 people), while those with the highest NT-proBNP had a rate of 1.4 percent (23 people).

At one year the researchers found that the mortality in group one was 1.8 percent (or 31 people); group two 3.9 percent (66); group three 7.7 percent (131); and group four 19.2 percent (327).

While recent research found that BNP increases considerably with age and is higher in women than men, this study found that baseline levels of NT-proBNP are also independently related to low body weight, kidney function and clinical factors indicating cardiovascular damage such as high blood pressure, previous heart attack or stroke, angina pectoris and diabetes mellitus. They found that it signaled risk independently of other risk factors, such as age and prior heart attack.

They reported that levels of troponin T and CRP also correlated independently with risk of death in the first year, but not as high as NT-proBNP.

NT-proBNP is a very useful biochemical marker for evaluation of patients with non-ST elevation acute coronary syndromes, James says.

"It can be used very early after symptom onset and very effectively predicts mortality in the short- as well as long-term. NT-proBNP can be used independent of renal function, or a history of heart failure or clinical signs of heart failure," he says.

In an accompanying editorial, David A. Morrow, M.D., M.P.H. and Eugene Braunwald, M.D., of Harvard Medical School and Brigham & Women's Hospital, Boston, Mass., write that this report adds substantially to accumulating evidence that a strategy to identify biomarkers is likely to improve risk assessment and clinical decision making to better the outcomes of patients with acute coronary syndrome.

Co-authors are: Bertil Lindahl, M.D., Ph.D.; Agneta Siegbahn, M.D., Ph.D.; Mats Stridsberg, M.D.; Per Venge, M.D., Ph.D.; Paul Armstrong, M.D.; Elliot S. Barnathan, M.D.; Robert Califf, M.D.; Eric J. Topol, M.D.; Maarten L. Simoons, M.D., Ph.D.; and Lars Wallentin, M.D., Ph.D.

For more information, or to contact American Heart Association, see their website at: www.americanheart.org