Download Administrative Office St. Joseph`s Hospital Site, L301

Administrative Office
St. Joseph's Hospital Site, L301-10
50 Charlton Avenue East
HAMILTON, Ontario, CANADA L8N 4A6
PHONE: (905) 521-6141
FAX: (905) 521-6142
http://www.fhs.mcmaster.ca/hrlmp/
Issue No. 46
QUARTERLY NEWSLETTER
Winter, 1999
TROPONIN I: A NEW MARKER OF CARDIAC INJURY
The diagnosis of acute myocardial infarction (AMI) is based on a patient history of characteristic chest pain,
diagnostic ECG changes and increases in the plasma concentration of biochemical markers of myocardial
injury.
The biochemical diagnosis of AMI is based on the fact that when cells are damaged or die due to lack of
oxygen, the cell membranes lose integrity and the cellular contents are released. It is important to remember
that myocardial necrosis is not a binary, all or nothing, event but a continuum ranging from reversible
membrane damage to cell death. Similarly, coronary ischemia is also not a binary event, but ranges from
stable angina to unstable angina to AMI.
The ideal biochemical marker of AMI has a diagnostic sensitivity and specificity of 100%, rises quickly after
the onset of the infarct, is rapidly available and is inexpensive. Few markers approach this ideal, none
achieve it.
The current generally used tests for the diagnosis of AMI depend on the assay of creatine kinase
isoenzymes. Creatine kinase is a muscle specific enzyme, present as a dimer. Two isoforms exist, muscle
(M) and the brain (B), thus the enzyme can exist in three isoenzyme types. CK-3 (CKMM) is predominant in
skeletal muscle. CK-2 (CKMB) is enriched in cardiac muscle, but is also present in significant amounts in
skeletal muscle. An increase in total CK activity, coupled with an increase in the proportion of CK-2 present,
forms the basis of the diagnosis of myocardial injury. Concomitant injury to skeletal muscle from trauma or
burns can cloud the picture and make the diagnosis difficult. Recently a number of candidate proteins have
emerged as replacements for total CK and CK-2.
The troponins (TnT, TnI, and TnC) are regulatory proteins located on the thin filament of the contractile
apparatus of skeletal and cardiac, but not smooth, muscle. Cardiac TnT (cTnT) and TnI (cTnI) isoforms differ
from their skeletal muscle counterparts by unique amino acid sequences. Cardiac forms of these proteins
are not expressed by skeletal muscle. Cardiac troponins are not normally present in the plasma of healthy
individuals or in those with non-cardiac diseases. Thus, the relative rise in plasma concentration after
myocardial injury of cTnT or cTnI is many times greater than that of total CK and CK-2, which circulate in the
plasma of healthy individuals. As a result, the troponins are sensitive and specific markers for even minor
myocardial necrosis. Troponin levels begin to rise 4-6 hours after the onset of the infarct, peak within 24-48
hours and remain elevated for 3-5 days in the case of cTnT and 7-10 days in the case of cTnI. This long
elevation makes the troponins useful in the evaluation of late presenting individuals, but can present a
problem for the diagnosis of re-infarct.
Troponin measurement has proven useful as a prognostic indicator to predict the risk of death in individuals
who present with both unstable angina and AMI. The risk of death was significantly greater at 30 and 42
days for individuals with increased cTnI (1), regardless of whether they were diagnosed with unstable angina
or with AMI, compared to those individuals without an increase. Thus, those individuals with unstable angina
and increased troponin levels should be placed in a similar risk category as those with documented infarct.
Troponin measurement systems are available from a number of manufacturers. Both near the patient and
laboratory-instrument formats are available. The former tend to be qualitative and expensive, while the latter
are, as a rule, quantitative and less expensive than the near patient formats. Because the different
manufacturers use different antibodies and standards in their assay formulations, it is important to remember
that the results from these different systems are not equivalent and not interchangeable.
The protocol recommended by the Hamilton Regional Laboratory Programme is to draw blood for total CK
activity and TnI at presentation and 6 (4-8), 12 (10-14), and 20 (18-24) hours after presentation. Total CK
activity is determined on all samples, and TnI until a diagnosis of AMI is established. Once this diagnosis is
established on the basis of a TnI greater than the diagnostic cutoff, no further TnI orders should be required.
Because the TnI may not begin to rise until 4-10 hours after the onset of the infarct, a rule out diagnosis of
AMI is unlikely in less than 12 hours.
This testing protocol replaces previous protocols for the biochemical evaluation of suspected AMI. As our
experience with the measurement and interpretation of the result increases, this protocol may be amended.
For further information on the use of troponins to assess cardiac injury or the above protocol, please contact
Dr. S. Hill (905) 527-0271, Extension 6045.
References
1. Elliot E.M., Tanasijevic M.J. Thompson B., Schatman M.S., et al. Cardiac-specific troponin I levels to
predict the risk of mortality in patients with acute coronary syndromes. N Eng J Med 1996; 335:1342-9.
Dr. S. Hill
Hamilton Regional Laboratory Medicine Programme
Hamilton General Division
Hamilton Health Sciences Corporation
The Hamilton Regional Laboratory Medicine Program is a collaborative program of the Hamilton Health
Sciences Corporation, St. Joseph's Hospital and McMaster University.
For further information concerning the Hamilton Regional Laboratory Medicine Program contact Mrs. Sue
Friend at (905) 521-6141.
For information on Community Laboratory Services please contact Mrs. Kathy Tiers (905) 521-6052, or the
Laboratory Reference Centre contact Mrs. Barb Baltzer at (905) 521-6065 or fax to (905) 528-1464.