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Ass. Prof.
Kari Pulkki, Ph.D.
Department of Clinical Chemistry, Helsinki University Central
Hospital,
Helsinki, Finland
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6.1 Aim
- To understand what are the clinical benefits and interpretation
of new cardiac markers and markers for heart failure.
- To introduce the evidence-based medicine in this context. EBM
also help in the discussion with the clinicians and in the reading
of published papers.
- What are the quality and turn-around-time requirements for
these tests?
6.2 History
Before the era of tests for the troponins, the diagnosis was
based on three components; clinical signs and symptoms, ECG-changes
and level of cardiac enzymes. As the evidence accumulated that a
small release of troponins (and CK-MB) is important as a prognostic
marker for the individual patients, this created the need for new
diagnostic criteria.
6.3 Present
Many tests, eg. for the measurement of cardiac troponin I, are
available. The standardisation and choice of antibodies of these
tests are essential; there are several-fold differences in measured
levels and also the time range for positivity is variable. The work
of the IFCC committee (C-SMCD) (Chairman Dr. Panteghini) is set to
decide the standardisation.
6.4 New markers
Both faster (fatty-acid binding protein) and more sensitive
tests (next-generation troponin tests) will be available. Also
tests which will detect plaque-rupture may be developed. Last year
the first paper to show the possibilities of pregrancy-associated
plasma protein A (PAPP-A) measurement was published. New markers
for platelet adhesion or markers to identify subgroups with
increased risk (natriuretic peptides; ANP and BNP for heart
failure) will be available. They should be analysed together with
established markers. If put in practice, they should show extra
benefit in the identification of new patients with increased risk,
in addition to the current markers. This would also create new
problems with the interpretation of these markers.
Some current examples and problems in evaluation of new cardiac
markers are introduced and discussed. The use of ROC curves in the
evaluation of new diagnostic tests is shown.
6.5 CRP
C-reactive protein is a non-specific marker for inflammation. As
a risk marker, slightly increased levels indicate risk for
cardiovascular death in the follow-up studies. In the early phases
of acute myocardial infarction, levels of 7-20 mg/l (depending on
the studies and patient groups) define patients with increased
risk, which is additional to the risk indicated by troponin levels.
This is, however, not easy to translate for the clinician, who will
make decisions. Smoking, other inflammatory diseases and other
life-style factors may influence these risk markers. Other
inflammatory markers studied include other acute phase proteins and
cytokines.
6.6 Organisation of
laboratory tests for acute heart diseases
Turn-around time (TAT) is interesting for the clinical unit as
they use the test results in order to make clinical decisions. It
depends on the individual organisation how they use it and what are
the requirements. There is a general requirement of 1 hour for TAT
set for cardiac markers if they are used for acute decisions.
Discussion between the laboratory and the clinical partners are
required to understand and discuss the use and availability of
these tests. If the requirements are not met, the clinical unit may
want organize their own tests, with point-of-care (POC) analysers.
In this setting it is advisable to organise the quality assurance
programme and user training schedules with the support of the
laboratory. Also the interface into the laboratory information
system (LIS) should be discussed.
6.7 Evidence-based
Medicicne (EBM)
The clinical use should be based on published, well-controlled
studies. This would result in the use of test-specific cut-offs and
decision limits. Correlation of one specific method with another
one is not enough, but clinical follow-up studies are needed. The
clinical end-points include cardiac death, interventions and
operations for cardiac disease and number of hospital admissions
etc. The clinical chemist/laboratory physician should be aware of
current published papers, as there are new tests continually being
produced. The analysis of patients in the paper is very essential,
including follow-up studies or other methods to define the clinical
outcome (eg. echocardiography for heart failure etc.). The
introduction of national or worldwide guidelines are important to
deliver a clear message.
6.8 Interpretation in
the clinic
The use of cut-offs for clinical decisions should be introduced
by the laboratory together with the clinical units (cardiology).
The use, TAT and availability should be clear for the clinicians.
The lag-time (before the rise in the serum level) after the onset
of pain or equivalent, the influence of ECG findings, heart
failure, renal failure and rhabdomyolysis should be discussed. The
new-generation tests (e.g. more sensitive troponin-tests) should be
considered, if they provide extra benefit for the
risk-evaluation.
6.9 Point-of-Care
(POC) tests
As the diagnostic industry is producing more and more new POC
tests and analytes, there is a need for the clinical chemist to
understand the evaluation of new tests that are markers for cardiac
diseases. The cut-off levels and decision limits of these tests
should also be based on clinical studies with relevant end-points
and follow-up studies. The available laboratory tests should be
considered as a relevant package, together with the clinicians
involved.
Recommended
literature:
- Myocardial infarction redefined - a consensus document of the
Joint European Society of Cardiology/ American College of
Cardiology Committee for the redefition of myocardial infarction.
Eur Heart J 2000; 21: 1502-13.
- Venge P, Lagerqvist B, Diderholm E, Lindahl, Wallentin and the
FRISC Group. Clinical performance of three cardiac troponin assays
in patients with unstable coronary artery disease. (a FRISC II
Substudy). Am J Cardiol 2002; 89:1035-41.
- Panteghini M, Gerhardt W, Apple FS, Dati F, Ravkilde J, Wu AH
Quality specifications for cardiac troponin assays. Clin Chem Lab
Med 2001; 39:175-9.
- Apple FS, Murakami M, Panteghini M, Christenson RH, Dati F,
Mair J, Wu AH. International survey on the use of cardiac markers.
Clin Chem 2001; 47:587-8.
- Panteghini M, Pagani F, Bonetti G. The sensitivity of cardiac
markers: an evidence-based approach. Clin Chem Lab Med 1999;
37:1097-106.
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