Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes

Christian Schulte; Bhawana Singh; Konstantinos Theofilatos; Nils A Sörensen; Jonas Lehmacher; Tau Hartikainen; Paul M Haller; Dirk Westermann; Tanja Zeller; Stefan Blankenberg; Johannes T Neumann; Manuel Mayr

doi:10.1016/j.jmccpl.2022.100014

Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes

Christian Schulte, Bhawana Singh, Konstantinos Theofilatos, Nils A Sörensen, Jonas Lehmacher, Tau Hartikainen, Paul M Haller, Dirk Westermann, Tanja Zeller, Stefan Blankenberg, Johannes T Neumann, Manuel Mayr

The British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, United Kingdom; Cardiovascular Division, James Black Centre, King's College Hospital Denmark Hill London, London, SE5 9NU, United Kingdom.
Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; German Centre of Cardiovascular Research (DZHK), Partner Site Hamburg, Luebeck, Kiel, Hamburg, Germany.
University of Freiburg
Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; German Centre of Cardiovascular Research (DZHK), Partner Site Hamburg, Luebeck, Kiel, Hamburg, Germany.; University Center of Cardiovascular Science, Hamburg, Germany.
Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; German Centre of Cardiovascular Research (DZHK), Partner Site Hamburg, Luebeck, Kiel, Hamburg, Germany.; Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies. We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types. Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67-0.84] for differentiating T1MI, T2MI and AI. Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI. [Abstract copyright: © 2022 The Authors.]

Original language	English
Pages (from-to)	None
Journal	Journal of molecular and cellular cardiology plus
Volume	1
DOIs	https://doi.org/10.1016/j.jmccpl.2022.100014
Publication status	Published - Sept 2022

Keywords

Biomarkers
Acute injury
Cardiac myosin-binding protein C
Troponin
microRNA
NT-proBNP
Myocardial infarction type 2

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10.1016/j.jmccpl.2022.100014

Cite this

Schulte, C., Singh, B., Theofilatos, K., Sörensen, N. A., Lehmacher, J., Hartikainen, T., Haller, P. M., Westermann, D., Zeller, T., Blankenberg, S., Neumann, J. T., & Mayr, M. (2022). Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes. Journal of molecular and cellular cardiology plus, 1, None. https://doi.org/10.1016/j.jmccpl.2022.100014

@article{a71784e317a442d08e5a841339c3313b,

title = "Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes",

abstract = "While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies. We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types. Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67-0.84] for differentiating T1MI, T2MI and AI. Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI. [Abstract copyright: {\textcopyright} 2022 The Authors.]",

keywords = "Biomarkers, Acute injury, Cardiac myosin-binding protein C, Troponin, microRNA, NT-proBNP, Myocardial infarction type 2",

author = "Christian Schulte and Bhawana Singh and Konstantinos Theofilatos and S{\"o}rensen, {Nils A} and Jonas Lehmacher and Tau Hartikainen and Haller, {Paul M} and Dirk Westermann and Tanja Zeller and Stefan Blankenberg and Neumann, {Johannes T} and Manuel Mayr",

year = "2022",

month = sep,

doi = "10.1016/j.jmccpl.2022.100014",

language = "English",

volume = "1",

pages = "None",

journal = "Journal of molecular and cellular cardiology plus",

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Schulte, C , Singh, B , Theofilatos, K, Sörensen, NA, Lehmacher, J, Hartikainen, T, Haller, PM, Westermann, D, Zeller, T, Blankenberg, S, Neumann, JT & Mayr, M 2022, 'Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes', Journal of molecular and cellular cardiology plus, vol. 1, pp. None. https://doi.org/10.1016/j.jmccpl.2022.100014

TY - JOUR

T1 - Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes

AU - Schulte, Christian

AU - Singh, Bhawana

AU - Theofilatos, Konstantinos

AU - Sörensen, Nils A

AU - Lehmacher, Jonas

AU - Hartikainen, Tau

AU - Haller, Paul M

AU - Westermann, Dirk

AU - Zeller, Tanja

AU - Blankenberg, Stefan

AU - Neumann, Johannes T

AU - Mayr, Manuel

PY - 2022/9

Y1 - 2022/9

N2 - While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies. We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types. Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67-0.84] for differentiating T1MI, T2MI and AI. Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI. [Abstract copyright: © 2022 The Authors.]

AB - While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies. We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types. Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67-0.84] for differentiating T1MI, T2MI and AI. Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI. [Abstract copyright: © 2022 The Authors.]

KW - Biomarkers

KW - Acute injury

KW - Cardiac myosin-binding protein C

KW - Troponin

KW - microRNA

KW - NT-proBNP

KW - Myocardial infarction type 2

U2 - 10.1016/j.jmccpl.2022.100014

DO - 10.1016/j.jmccpl.2022.100014

M3 - Article

C2 - 36185590

SN - 2772-9761

VL - 1

SP - None

JO - Journal of molecular and cellular cardiology plus

JF - Journal of molecular and cellular cardiology plus

ER -

Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes

Abstract

Keywords

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