Metabolomic Analysis of Patients with Coronary Artery Disease and Acute Myocardial Infarction by Using Nuclear Magnetic Resonance Spectroscopy

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Coronary artery disease (CAD) and acute myocardial infarction (AMI) (n=134). Intervention: Acute myocardial infarction (AMI) evaluated via serum Nuclear Magnetic Resonance (NMR) metabolomic profiling vs. Stable coronary artery disease (CAD) with >=50% coronary artery stenosis. Primary outcome: Serum lactic acid level difference (CAD vs AMI) and random forest metabolomic classification accuracy (log2 fold change -1.533 (Cliff's delta -0.792); Random forest pooled AUC 0.9, 95% CI -1.825 to -1.215, p=9.96e-13).

Q: What does this research mean for the field?

NMR-based serum metabolomic profiling distinguishes acute myocardial infarction from stable coronary artery disease, driven predominantly by elevated levels of lactic acid and hypoxanthine. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Nikolaos Pagonas; Werner Dammermann; GERASIMOS SIASOS; Sawa Kostin; Benjamin Sasko; Philipp Sotiriou; Selina Strathmeyer; Steffen Heelemann

doi:10.1007/s12265-026-10866-5

November 3, 2026Journal of Cardiovascular Translational ResearchOpen Access

Metabolomic Analysis of Patients with Coronary Artery Disease and Acute Myocardial Infarction by Using Nuclear Magnetic Resonance Spectroscopy

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Key result

NMR metabolomics distinguishes AMI from stable CAD with ~0.9 AUC, driven by lactic acid.

log2 fold change -1.533 (Cliff's delta -0.792); Random forest pooled AUC 0.9
95% CI -1.825 to -1.215
P 9.96e-13
n=134

Why the study?

The potential of Nuclear Magnetic Resonance spectroscopic metabolomic analysis to differentiate between stable coronary artery disease and acute myocardial infarction required investigation.

Does NMR-based serum metabolomic profiling differentiate between stable coronary artery disease and acute myocardial infarction?

Key Points

Investigate whether nuclear magnetic resonance spectroscopy-based metabolomic profiling can differentiate between stable coronary artery disease and acute myocardial infarction.
Conducted a cross-sectional exploratory study analyzing serum samples from 82 patients with coronary artery disease (≥50% diameter stenosis) and 52 patients with acute myocardial infarction.
Profiled 76 serum metabolites using 1D 1H nuclear magnetic resonance (NMR) spectroscopy on a 600 MHz spectrometer.
Assessed metabolite alterations using the Wilcoxon rank-sum test with Benjamini-Hochberg false discovery rate correction, alongside supervised PLS-DA and random forest modeling.
Identified distinct serum metabolic profiles distinguishing stable coronary artery disease from acute myocardial infarction.
Lactic acid, an end-product of anaerobic glycolysis, was identified as a prominent marker in acute myocardial infarction reflecting acute ischemic stress.
Hypoxanthine was highlighted as a key biomarker indicative of myocardial ischemia.

Study Design

Type

Cross-Sectional (n=134)

Multicenter

No

Structured PICO

Does NMR-based serum metabolomic profiling differentiate between stable coronary artery disease and acute myocardial infarction?

P

Population

134 adults (mean age ~71-72 years, 71.6% male) with stable coronary artery disease (n=82) or acute myocardial infarction (n=52) undergoing coronary angiography at a single German hospital.

E

Exposure

Serum metabolomic profiling using 1D 1H Nuclear Magnetic Resonance (NMR) spectroscopy (Bruker AVANCE NEO 600 MHz) combined with supervised multivariate analysis (PLS-DA), random forest machine learning classification, and KEGG pathway enrichment analysis.

C

Comparator

Direct metabolomic comparison between patients with acute myocardial infarction (AMI, n=52) and patients with stable coronary artery disease (CAD, n=82).

O

Outcome

Differentiation of serum metabolic profiles and identification of significantly altered metabolite concentrations between stable CAD and AMI patients.surrogate

Main Result

Effect estimate: log2 fold change -1.533 (Cliff's delta -0.792); Random forest pooled AUC 0.9 (95% CI -1.825 to -1.215)

p-value: p=9.96e-13

NMR-based serum metabolomics can accurately differentiate acute myocardial infarction from stable coronary artery disease (AUC 0.90), driven by key ischemic markers including lactic acid, hypoxanthine, formic acid, glutamic acid, and phenylalanine.

Limitations

Exploratory cross-sectional study design
No independent external validation cohort was available
Clinical outcomes associated with higher lactic acid levels were not investigated in the study population
Further large-scale studies are necessary to validate findings
No independent external validation cohort was available, so PLS-DA and random forest results are considered internally assessed and exploratory
Adverse clinical outcomes in patients with higher lactic acid levels were not investigated in this study population
Further large-scale studies are necessary to validate these findings and incorporate them into clinical practice

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Implication

Hypothesis-generating for NMR metabolomics in AMI; requires prospective validation before clinical consideration.

Abstract

This cross-sectional exploratory study investigates the potential of metabolomics to differentiate between stable coronary artery disease (CAD) and acute myocardial infarction (AMI) through Nuclear Magnetic Resonance (NMR) spectroscopic analysis. The study identifies distinct metabolic profiles for each condition, revealing significant variations in metabolite levels, particularly lactic acid, which is a key metabolic product of anaerobic glycolysis, emerges as a prominent marker in AMI patients, reflecting acute ischemic stress and providing insight into adverse outcomes associated with high lactate levels. Another metabolite found in the present study was hypoxanthine, which is key biomarker for myocardial ischemia. These findings underscore the potential of metabolomics in combination with pathway analysis in distinguishing between CAD and AMI and highlight the metabolic dysregulation that occurs in these diseases. Our results suggest that these metabolites could serve as potential biomarkers, paving the way for personalized prognostic and diagnostic strategies. Further large-scale studies are necessary to validate these findings and incorporate them into clinical practice.

Discussion

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Cite This Study

Pagonas et al. (2026) conducted a cross-sectional in Coronary artery disease (CAD) and acute myocardial infarction (AMI) (n=134). Acute myocardial infarction (AMI) evaluated via serum Nuclear Magnetic Resonance (NMR) metabolomic profiling vs. Stable coronary artery disease (CAD) with >=50% coronary artery stenosis was evaluated on Serum lactic acid level difference (CAD vs AMI) and random forest metabolomic classification accuracy (log2 fold change -1.533 (Cliff's delta -0.792); Random forest pooled AUC 0.9, 95% CI -1.825 to -1.215, p=9.96e-13). NMR metabolomic profiling distinguished AMI from stable CAD with a pooled AUC of 0.9, driven by elevated lactic acid (log2FC -1.533, p=9.96e-13) and hypoxanthine (p=1.27e-11) in AMI.

synapsesocial.com/papers/6aebc8ba3e63ca1b6c315e2f https://doi.org/10.1007/s12265-026-10866-5

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Metabolomic Analysis of Patients with Coronary Artery Disease and Acute Myocardial Infarction by Using Nuclear Magnetic Resonance Spectroscopy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Metabolomic Analysis of Patients with Coronary Artery Disease and Acute Myocardial Infarction by Using Nuclear Magnetic Resonance Spectroscopy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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