Nov. 15, 2001 ANAHEIM, Calif. – Patients who test positive for the presence of a specific biochemical marker of heart cell death in their blood but who do not exhibit other risk factors for future heart attack should be treated as higher risk patients, according to a new analysis by cardiologists at Duke University Medical Center.
The researchers found that troponin, a protein that is released into the bloodstream as heart muscle cells die, can be a reliable indicator of future risk even when other traditional measures of heart health are negative. This is important, the researchers say, in light of the recent recasting of the definition of heart attack by the major cardiology organizations to place more emphasis on the results of troponin testing, in addition to the presence of chest pain and electrocardiogram abnormalities.
When a patient comes to the emergency room as a possible heart attack victim, physicians typically measure the heart's electrical activity (EKG) and also look for chemicals in the blood that might indicate if heart muscle is damaged or dead. For years, they have measured the levels of creatine kinase-MB (CK-MB) and, more recently, they also have been testing for troponin. Because the test for troponin can detect even small amounts of heart muscle damage, patients previously testing positive for troponin but negative for CK-MB were not always treated as being at high-risk.
"Our analysis shows that patients who test positive for troponin but not for CK-MB should still be treated as if they tested positive for both," said Duke cardiology fellow Dr. Sunil Rao. "This is important because in the past, these patients would usually not be treated aggressively."
Rao prepared the results of his study for presentation during the 74th annual scientific sessions of the American Heart Association. Both troponin and CK-MB are proteins within cells that spill out into the bloodstream as the cell wall breaks apart during cell death. The difference between the two is that troponin is only released by heart muscle, while CK-MB can be released by both dying heart and skeletal muscle.
"We believe that even low levels of troponin in the bloodstream indicate the presence of tiny heart attacks, or infarctlets," Rao explained. "The question is, does the death of a few heart cells matter, and can they be a reliable predictor of larger infarctions, or heart attacks, in the future?"
According to the Duke analysis, it does matter.
Rao and colleagues scoured the data collected from three different multi-center trials to measure the prognostic value of elevated and isolated troponin levels. Two of trials – PARAGON-B and GUSTO IIa – followed high-risk heart attack patients, and the other, CHECKMATE, looked at low-risk patients.
Patients were divided into three groups – those who were positive for both troponin and CK-MB, those who were positive for only troponin, and those positive only for CK-MB. The team found the incidence of death or heart attack after 30 days was the same for patients who only tested positive on the troponin test as for those who tested positive on both.
The researchers feel that the troponin test, which is an extremely specific and sensitive indicator of cardiac cell damage, can help physicians detect those patients who would be described as low-risk, but who actually are at a higher-risk of future cardiac events. They would even argue that troponin levels should be used instead of CK-MB in the definition of heart attack.
"For patients who come in with chest pain, EKG abnormalities and elevated markers, it is a straightforward decision to admit them to cardiac care units and begin treatment," said Duke cardiologist Dr. Kristin Newby, senior member of the research team. "However, there are many patients who may have some chest pain and unremarkable EKGs, so the chemical markers become an important determinant in how we treat them. Based on this analysis, for those with apparently ischemic symptoms, we should place equal emphasis on aggressively managing patients with only troponin elevation as on those with elevations of both markers.
"The risk of future cardiac events appears to be proportionate to degree of elevation of cardiac markers like troponin – so any elevation means risk," Newby said. "Any cell death, even if small, can be a powerful indicator of future bad events."
Other members of the Duke team were Vic Hasselblad, Robert Christenson, Dr. W. Brian Gibler, Dr. Christopher Granger and Dr. Magnus Ohman. The data analysis was supported by the Duke Clinical Research Institute.
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