Increased blood levels of a heart cell “stress” protein called ST2 were linked to a higher risk of death

Apr 29 2004

“The significance of the data is twofold,” said Richard T. Lee, M.D., lead author of the study and associate professor of medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston.  “First, the data suggest that this pathway of inflammation may occur in the early events of heart attack.  Second, ST2 levels provide a novel biomarker that can offer prognostic information on heart attack victims, independent of the usual clinical predictors.”

The ST2 protein is linked to immune system responses and inflammation.  Researchers had previously shown that “stressed-out heart cells” produce the ST2, Lee said.  Blood levels increase in patients after heart attack, peaking about 12 hours after the event.  Researchers also had found that ST2 is associated with worse outcomes in non-ischemic heart failure, but its predictive value in acute myocardial infarction had not been studied.

“The big picture is that despite all the things we do for heart attack patients, some will go on to die or develop heart failure,” Lee said.  “We need more tools in our toolbox to not only pick out those patients who may do worse, but also to stop the development of heart failure.”

Researchers measured levels of the ST2 protein in patients participating in the Thrombolysis in Myocardial Infarction (TIMI) 14 and TIMI 23 clinical trials.  The study of 810 patients with heart attacks found that the initial levels of ST2 were significantly higher in patients who later died or who developed new or worsening congestive heart failure within 30 days after a heart attack.  When the researchers divided the ST2 levels into graded quartiles, death and combined death/heart failure showed a significant graded association with levels of ST2.

Heart attack patients in the highest quartile of ST2 levels were seven times more likely to die within 30 days after heart attack than patients with the lowest quartile levels.  When death and heart failure were combined, those with the highest levels of ST2 had a four-fold increased risk of death or congestive heart failure compared to those with lower levels.

When other risk factors were controlled for – such as age, blood pressure, heart rate and location of heart attack – the researchers found that increased levels of ST2 remained an independent predictor of death after heart attack.

Patients entered the study between 1998 and 2001.  They had chest pain for 30 minutes in the past six to 12 hours and had evidence of acute myocardial infarction (heart attack) on their electrocardiograms.  Blood levels of ST2 were collected at baseline and at one, three, 12 and 24 hours after the heart attack.  Levels were then divided into four groups, or “quartiles.”

Both increased heart rate and higher systolic blood pressure were associated with elevated ST2 levels, supporting the theory that ST2 is secreted by cardiac muscle cells under stress.

Researchers believe the protein receptor is induced in conditions of myocardial overload such as heart attack, when the remaining living heart muscle must work harder to make up for the dying tissue.  A similar overload occurs in the progression of heart failure, where ST2 levels are associated with the patient’s prognosis.

Heart muscle cells rapidly secrete one form of this protein when they become mechanically overloaded, Lee said.  “When some heart muscle dies during the heart attack and the living heart muscle is stretched, the heart cells put out more ST2.”

An inflammatory response from damaged tissues may further stimulate the production of the protein in neighboring cells.

A blood test for ST2 may help predict the prognosis of patients after a heart attack, but measuring ST2 will not help in diagnosing heart attacks, the researchers said.  This is because not just heart muscle cells can secrete ST2.  For example, patients with asthma can also have increased levels of ST2 in their blood.

“We have a lot to learn, but we are excited about any new tool that could help in the prognosis of patients after a heart attack,” Lee said.