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Press releases

Biomarker could improve prediction of recurrent heart attacks and death

In der DZHK-Biobank lagert Blutserum von Herzschwäche-Patienten: Es könnte dabei helfen, einen neuen Biomarker, der beim Herzinfarkt eine Rolle spielt, besser zu verstehen. Denn zwischen den beiden Erkrankungen gibt es Parallelen. |© TippaPatt - stock.adobe.com

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Scientists at the German Center for Cardiovascular Research (DZHK) have discovered a new biomarker for estimating the risk of another heart attack or death after an index heart attack. The biomarker 'Cellular Communication Network Factor 1' (CCN1), which can be measured in blood serum, improves the prognostic accuracy of the clinical GRACE score.

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If a patient comes to the emergency room with acute chest pain, it is often an acute heart attack. After an acute heart attack, it is not uncommon that the patient will experience   another heart attack or may even die. The doctors must quickly gauge the risk for future adverse events with the aim to initiate optimal treatment. Dr Roland Klingenberg from the Kerckhoff Klinik in Bad Nauheim, has discovered a new biomarker (CCN1) that improves the predictive power of the established risk score (GRACE score).

The so-called GRACE score calculates how likely it is for people who have had an acute heart attack to experience another heart attack or to die in the near future.  Risk assessment makes it possible to identify patients at high risk which is the foundation for optimal treatment.  In addition to patient data, such as age, heart rate, blood pressure, already established cardiac  biomarkers, for example, troponin, is included in the calculation.

The biological mechanism of the biomarker is still unclear

In prior investigations of heart attack patients, tissue from coronary blood clots could be obtained, which the researchers investigated using gene expression analyses. They showed that the biomarker CCN1 was found more strongly expressed in the tissue of the blood clots than in circulating blood cells. In addition, recent  analyses show an additional independent benefit of CCN1 beyond established biomarkers hsTnT, NT-proBNP and hsCRP combined with the GRACE score in the risk stratification of patients with an acute heart attack. This suggests that CCN1 reflects  a previously unknown pathophysiological mechanism.

"We cannot say at this point which disease aspect the biomarker mirrors exactly", Klingenberg explains. Therefore, the biomarker is currently not included in the calculation of the risk score. As long as the  underlying disease-specific pathology  is unknown,  physicians cannot tailor treatment accordingly to address this pathology which is reflected by the biomarker .

DZHK biobank is a huge treasure trove of data

Together with other scientists, Roland Klingenberg now wants to investigate the new biomarker CCN1 in detail. They want to understand the underlying mechanisms that lead to CCN1 being found in  high levels in  blood serum after a heart attack. To do this, the researchers compare the data they have already obtained from patients with acute coronary heart disease with patients suffering from heart failure (dilated cardiomyopathy).

Since there are parallels between these two diseases, the researchers hope to gain new insights. For example, inflammatory processes and pathological changes in the connective tissue (fibrosis) occur in both cases. A biobank which was set up by the DZHK can help scientists gain new insights into the significance of CCN1 in the disease process.

This biobank collects medical data and biomaterials from patients who have participated in DZHK studies. These data and samples are also available for other scientists from outside DZHK upon request. "Material from patients with dilated cardiomyopathy exists in the DZHK biobank, which we can now use for our research question and  to validate data from a pilot study in patients at the University of Greifswald," says Klingenberg.

In a current study, Klingenberg and his team examine the blood serum of about 400 patients from the DZHK biobank using proteomics analysis. He and his colleagues hope to gain a deeper understanding of the biomarker's function to improve treatment options for cardiovascular patients.


Original publications:
Cysteine-rich angiogenic inducer 61 (CCN1) improves prognostic accuracy of GRACE 2.0 risk score in patients with acute coronary syndromes. Klingenberg R, Aghlmandi S, Räber L, Akhmedov A, Gencer B, Carballo D, Nanchen D, Bucher HC, Rodondi N, Mach F, Windecker S, Landmesser U, von Eckardstein A, Hamm CW, Lüscher TF, Matter CM. JAHA 2021; in press.

Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes. Klingenberg R, Aghlmandi S, Liebetrau C, Räber L, Gencer B, Nanchen D, Carballo D, Akhmedov A, Montecucco F, Zoller S, Brokopp C, Heg D, Jüni P, Marti Soler H, Marques-Vidal PM, Vollenweider P, Dörr O, Rodondi N, Mach F, Windecker S, Landmesser U, von Eckardstein A, Hamm CW, Matter CM, Lüscher TF. Eur Heart J. 2017 Dec 14;38(47):3493-3502. doi: 10.1093/eurheartj/ehx640.

Christine Vollgraf, Press and Public Relations, German Centre for Cardiovascular Research (DZHK), Tel: 030 3465 529 02, presse(at)dzhk.de 

Scientific Contact:
Priv.-Doz. Dr. med. Roland Klingenberg, Kerckhoff-Klinik, Klinik für Kardiologie und Kerckhoff Herzforschungsinstitut mit der JLU Gießen, r.klingenberg(at)kerckhoff-klinik.de