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| Issue 6 1999 |  |
| NEW MARKERS FOR CORONARY ARTERY DISEASE |
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Renze
Bais Express Laboratory, PaLMS Contact: tel +61 2 9926 7464 e-mail: rbais@med.usyd.edu.au |
| Despite recent advances
in elucidating the mechanisms involved in atherosclerosis, cardiovascular
disease continues to be a major cause of death in most countries. Even
with changes in lifestyle and the use of new pharmacological approaches
to lower cholesterol concentrations, the incidence remains extremely high.
Cardiovascular disease is multifactorial and a recent review described
the lesions of atherosclerosis as representing a series of highly specific
cellular and molecular responses that can best be described as an inflammatory
disease.
Myocardial damage can be detected by the measurement of normal intracellular constituents of the myocardium which appear in the blood stream. Historically, three enzymes, aspartate aminotransferase, creatine kinase, lactate dehydrogenase and their isoenzymes have been used to identify myocardial necrosis. Although the isoenzymes are more specific than these three enzymes, they can also be raised in other conditions. For instance, the CK-MB isoenzyme of creatine kinase has for many years been the favoured marker of acute myocardial infarction but this isoenzyme can be present as up to 2% of the total creatine kinase in skeletal muscle and thus can be raised in other conditions. For example, in a patient undergoing surgery, the level of total creatine kinase can be 10,000 U/L which could include up to 200 U/L of the CK-MB isoenzyme. Another problem with these traditional markers is their relatively slow release kinetics. Total creatine kinase and the CK-MB isoenzyme may not reach a peak until at least 18 hours after the onset of the myocardial infarction and it is about 6 hours before any change in activity can be detected by the current methods used in the laboratory. Thus, there has been a continuing search for both rapid and specific markers of cardiac damage. In theory, with the advent of sensitive immunoassay procedures, any cardiac molecule could potentially be used as a marker molecule. The two favoured new markers for cardiac damage are myoglobin and troponin. Myoglobin is a monomeric haem-containing, 18,000 dalton molecular weight protein that normally transports oxygen in mammalian muscles. The protein is found in the cytosolic faction of both cardiac and skeletal muscle tissue. These forms are indistinguishable and there are no myoglobin isoenzymes. Because of its small size and relatively high tissue concentration, very rapid and pronounced increases are seen after skeletal and/or cardiac damage. The protein is excreted in the urine and clears rapidly from the blood. Numerous studies have demonstrated the rapid elevation of myoglobin after an acute myocardial infarction, with peak levels occurring between 6 and 8 hours after the occlusion of a coronary artery. However, because of its high tissue concentration, increases in myoglobin can be measured in the laboratory much earlier than at the peak level and in many cases within 1 hour of the cardiac event. Thus, myoglobin is an early marker of cardiac damage but lacks the specificity of an ideal marker. The current most specific markers for cardiac damage are troponin T and troponin I. Troponin T and I are myofibrilar proteins of the thin filament and are present both as a minor cytosolic and a major structural bound protein pool. These markers show release characteristics of both free cytosolic and structural proteins, the peak level in the blood occurring at 18-24 h (similar to CK and CK-MB) and often still detectable 12 days post-infarction. There has been a great deal of debate on which is the most specific form of troponin and if either of these isoforms are raised in conditions not involving cardiac damage. The answer is that false positives probably occur for both isoenzymes but they are relatively uncommon and troponin is by far the most specific marker currently available. Which form should be chosen is more dependent on the equipment in the laboratory rather than the utility of either marker. The comparable release patterns of the major markers of cardiac damage are shown in Figure 1 below: |
 Myoglobin ( Myo ) Creatine Kinase-MB fraction ( CKMB ) Troponin T ( TnT ) Tropinin I ( TnI ) Lactate Dehydrogenase ( LD ). Diagram supplied courtesy of Roche Diagnostics. |
The recommendation
on the use of these new markers has been summarised in a discussion
paper published by the National Academy of Clinical Biochemistry in
which the authors list a series of recommendations. The most relevant
are:
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| Because of their specificity and with the advent of second generation
more sensitive assays, it has been found that the level of troponin can
be used in the risk stratification of patients with unstable angina. Unstable
angina represents a critical phase of ischaemic heart disease and is associated
with significant risk of subsequent myocardial infarction or death. A number
of studies have now shown that the presence of troponin in the serum of
patients with unstable angina can identify a group of patients without classical
AMI but likely to have a major cardiac event (non-fatal myocardial infarctions
or cardiac death). The availability of cardiac markers from PaLMS is summarised below . Currently, troponin T is available in the PaLMS Express Laboratory at Royal North Shore Hospital. Assays for myoglobin are being assessed and should be introduced in the near future. In conjunction with the Emergency Department at Hornsby Hospital, we have trialed a point-of-care device for measuring both myoglobin and troponin T and it has been decided to introduce this to the Emergency Departments of Hornsby, Manly, Mona Vale and Ryde Hospitals. Both troponin T and I are now in the Medical Benefits Schedule (Item 66518). It should, however, be noted that the schedule states: |
| CK and CK-MB | Available from PaLMS Express Laboratories at Hornsby, Manly, Mona Vale, Royal North Shore and Ryde Hospitals. |
| Troponin T | Available from PaLMS Express Laboratory
at Royal North Shore Hospital. Note: PaLMS has introduced point of care testing for Troponin T into the Emergency Departments of Hornsby and Manly Hospitals and will introduce it into the Emergency Departments of Mona Vale and Ryde Hospitals in the near future. |
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Myoglobin Assays are currently being assessed. |
In the near future, myoglobin measurement should be introduced into the PaLMS Express Laboratory at Royal North Shore Hospital. |
| AST, LD and LD isoenzymes | Not recommended in diagnosis of cardiac disease. |
| The measurement of troponin and myoglobin is significantly more expensive than the traditional enzyme markers and CK-MB and thus, they should not be done indiscriminately. For example if the patient has characteristic ECG changes there is no need to order either of these tests. Finally, to assess a patient who presents with chest pain without a characteristic history and ECG changes, a protocol that could be used is shown in Figure 2 below: |
Further Reading
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| NEWS FROM PaLMS |
| At PaLMS we are constantly striving to meet our customer’s needs. There really is a sense of excitement as we expand our current services and prepare to launch new services. We are particularly happy to announce... |
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PaLMS Customer Relations Manager phone: +61 2 9926 8086 e-mail: mhardy@doh.health.nsw.gov.au |
