Biomarkers are diagnostic game changers

Professor Holdenrieder: ‘Obviously the good news is that sensitivity, and thus the quality of biomarker tests for the early diagnosis of cardiac diseases, is constantly improving. Moreover, the change of marker levels and combinations of markers are increasingly used in diagnostics to obtain even more precise results.’

Does this mean diagnostics is like a veritable orchestra with various instruments?

‘Correct. With regard to cardiac diseases new biomarkers, such as copeptin, are on the rise, complementing troponin since they provide results faster – an important factor particularly in the emergency room.’

But troponin is here to stay?

‘Absolutely, particularly since today we have highly sensitive troponin tests that can diagnose a myocardial infarction within half an hour. The crucial advantage of highly sensitive tests is the fact that they measure even low values very precisely. Troponins take a while, until they increase significantly.

Before, a patient with symptomatic chest pain, but unsuspicious ECG and unsuspicious troponin values had to wait for about three hours until a new test showed the troponin changes. The new and highly sensitive tests can show changes after only an hour – if a myocardial infarction has happened. This allows us to either intervene early or, if the values are unsuspicious, confirm that there was no cardiac event and we can send the patient home. This new type of test is faster and more precise. Equally important – with the help of troponins we can detect previous damage to the heart.’

These highly sensitive tests are not yet available in Germany?

'Indeed. Having said that, many medium size labs are already equipped with the analytic tools required for these tests. Processing the tests is simple and not particularly expensive. Nevertheless, there are places where the tests cannot yet be applied, such as in your doctor’s (GP’s) surgery. Today, no POCT units are available that can use these highly sensitive tests. The development of such POCT tools will play a major role in the future.’

Since troponin can be measured with such high precision, will other markers, such as copeptin, still be needed?

Professor Stefan Holdenrieder, Director of the Institute of Laboratory Medicine at Munich’s German Heart Centre.

‘Yes, in the case of a disease we try to intervene as early as possible. There is still a gap between the onset of symptoms and detection of troponin, or rather the onset of the therapy. During this time gap there is a risk of the coronary vessels being obstructed. Copeptin can help us get through this phase because it’s a pro-hormone, which, in a stress situation, is released by the hypophysis within minutes.

Obviously the stress can be triggered by a number of events, be it an accident, inflammation or infarction. Usually copeptin is already elevated when troponin is still unsuspicious. Thus copeptin gives us important time to prepare treatment. While the marker does not confirm the diagnosis myocardial infarction it does offer an important warning signal of a cardiac event. ‘If, by the same token both copeptin and troponin values are unsuspicious, we can say with 99 percent likelihood that no myocardial infarction happened.’

Where else can biomarkers be used?

‘In cardiology there are two reliable biomarkers that indicate cardiac insufficiency: the peptide BNP and the precursor fragment NT-proBNP. Both indicate the degree to which the heart muscle cells are stretched. Increased myocardial wall tension is a clear indicator of cardiac insufficiency. Increased markers are a serious alarm signal. However, for the initial diagnosis it is irrelevant which marker is being measured.

BNP has a shorter half-life in the blood, thus the NT-proBNP value is more precise. With acute heart failure, though, both values are increased. Moreover, both values are used for risk assessment and follow-up. Since certain therapies affect BNP metabolisation, NT-proBNP is the marker of choice to measure outcome: When NT-proBNP decreases, the therapy is effective. Further promising markers are in the pipeline, such as ST2, galectin-3 or GDF-15.’

What role will biomarkers play in the future?

‘The potential of biomarkers is far from exhausted. Currently a number of studies are investigating which biomarker categories can be used for which types of clinical issues. Generally speaking, biomarkers can play a role in genetics, epigenetics, with micro-RNAs or exosomes, lipids, proteins or as metabolomic markers, or any combination of biomarkers. There are many and various possibilities. We are charting new territory here and further exploring the potential will require large-scale studies and handling of huge data volumes. New diagnostic technologies open up new horizons with regard to understanding the development of arteriosclerosis and cardiovascular disease. However, meticulous assessment of diagnostic findings is crucial to determine a suitable treatment that will help the patient.’

Profile:

With previous roles at the Institute for Clinical Chemistry and Clinical Pharmacology at Bonn University, and the Institute for Clinical Chemistry at Munich University, today Professor Stefan Holdenrieder is the Director of the Institute of Laboratory Medicine at Munich’s German Heart Centre. His research focus lies on the development and evaluation of new laboratory diagnostic biomarkers and technologies for cardiology, oncology, immunology and neurology, with an additional special focus on circulating nucleic acids and their genetic and epigenetic changes.

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Professor Stefan Holdenrieder, Deutsches Herzzentrum München and Universität Bonn

13.11.2017

• biomarkers (130)
• diagnostics (460)
• laboratory (1043)