Clin Res Cardiol (2022).

Multi-biomarker model to differentiate type 1 from type 2 acute myocardial infarction
M. El-Hirch1, J. Bormann2, C. Lipps1, J. S. Wolter2, M. Weferling2, S. Kriechbaum2, O. Dörr3, H. Nef3, C. W. Hamm3, C. Liebetrau4, B. von Jeinsen2, T. Keller5
1Kardiologie und Angiologie, Justus-Liebig-Universität Giessen, Gießen; 2Abteilung für Kardiologie, Kerckhoff Klinik GmbH, Bad Nauheim; 3Medizinische Klinik I - Kardiologie und Angiologie, Universitätsklinikum Gießen und Marburg GmbH, Gießen; 4CCB am AGAPLESION BETHANIEN KRANKENHAUS, Frankfurt am Main; 5Franz-Groedel-Institut (FGI), Justus-Liebig-Universität Giessen, Bad Nauheim;


High-sensitive cardiac troponins (hs-cTnI and hs-cTnT) are the gold standard to detect an acute myocardial infarction (AMI) and they play a central role in the definition of all five types of AMI. While patients who suffer from a type-1 AMI profit from an early invasive treatment, coronary angiography might not be indicated in patients with type-2 AMI. We investigated multi-marker models including several biomarkers representing different pathophysiological aspects of an AMI in addition to cardiac troponins to differentiate between type-1 and type-2 myocardial infarction. 



We analyzed 261 AMI patients (type-1 AMI n = 231; type-2 AMI n = 60) who were prospectively enrolled into a biomarker register. Mean age was 69.5 and 31.4 % were female. We designed two Multi-Marker Models (MMM) to differentiate type-1 from type-2 AMI: Both MMM contained calprotectin, copeptin, and c-reactive protein (CRP). MMM-1 additionally contained hs-cTnI and brain-natriuretic peptid (BNP), while MMM-2 contained hs-cTnT and N-terminal BNP (NT-proBNP). 


The biomarkers copeptin, calprotectin, and CRP levels were significantly lower in type-1 AMI vs. type-2 AMI with median calprotectin of 2.5ng/ml [1.5ng/ml-4ng/ml]  vs. 3.57ng/ml [1.88ng/ml- 6.55ng/ml] (p=0.006). Median Copeptin levels were 9.23pmol/L [5.05pmol/L-25.66pmol/L] vs. 19.06pmol/L [7.7pmol/L-45.17pmol/L](p=0.003) and median CRP levels were 0.3mg/L [0.2mg/L-1.1mg/L] vs. 0.6mg/L [0.3mg/L-1.4mg/L](p=0.022), respectively. 

In contrast hs-cTnI levels and hs-cTnT levels were higher in type-1 AMI compared to type-2 AMI with hs-cTnI of 464.3pg/ml [75.8ng/L -2028.05ng/L] vs. 50.2 ng/L [11.82 ng/L- 339.2 ng/L](p<0.001) and hs-cTnT of 102.3ng/L [34.05ng/L-301.3ng/L] vs. 47.25ng/L [22.62ng/L-137.65ng/L] (p=0.001). Both natriuretic peptides tend to be higher in type-2 AMI without reaching statistical significance (pBNP=0.153; pNTproBNP=0.227).

The individual biomarkers were able to differentiate type-1 from type-2 AMI with areas under the receiver operater characteristics curve (AUROC) ranging from 0.551 to 0.709  with 0.709 for hs-cTnI, 0.639 for hs-cTnT, 0.615 for calprotectin, 0.632 for copeptin, 0.596 for CRP, 0.551 for BNP and 0.560 for NT-proBNP.

Combination of these biomarkers into multimarker models improved the discriminatory information with an AUROC of  0.773 for MMM1 and an AUROC of 0.755 for MMM2 to differentiate type-1 AMI from type-2 AMI. 


In contrast to cardiac troponins, levels of copeptin, calprotectin, and CRP, representing other pathophysiological aspects of an AMI than necrosis, were significantly lower in patients with type-1 AMI compared to patients with type-2 AMI. 

A combination of different biomarkers in multi marker models improves diagnostic differentiation between types of AMI compared to the diagnostic information of the individual markers alone and therefore might help to streamline patients with suspected AMI to invasive treatment.