The Metabolic Profile of Stable Ischemic Heart Disease by Serum 1H NMR

Abstract

Ischemic heart disease (IHD) is the most common cause of death in the world. Metabolic profiling is an innovative and reliable new method to detect more sensitive biomarkers identifying altered health conditions specifically among the variety of patients with different risk factors. We evaluated the metabolic profile of filtered serum of stable IHD patients (ICD10 codes I20 and I25.2, ischemic heart disease without or with previous myocardial infarction respectively) using proton nuclear magnetic resonance spectroscopy (NMR). The filtered venous serum from age- and gender-matched stable IHD patients ICD10 coded I20 (n = 13), I25.2 (n = 6) and control individuals (n = 19) were analyzed using one-dimensional proton nuclear magnetic resonance (1H NMR) spectroscopy. These spectra were used for metabolic profiling and concentration calibration (Chenomx Inc.) followed by statistical analysis using one-way ANOVA and principal component analysis (PCA). Chemometrics analysis showed a significant distinction between the patients and control individuals. The stable IHD patients were exemplified by the increased concentration of acetylacetate, choline, betaine, formate, pyruvate and by the decreased concentration of alanine, creatine, glycine, histidine, lactate, proline, urea and other biomolecules. The major implications found in the serum of IHD patients are related to energy metabolism and potentially altered microbiome. PCA of 1H NMR detected serum metabolites exhibit a significant difference of stable IHD patients and control individuals. These data demonstrate that metabolomics approach may be useful for the early detection of stable IHD, for detection of synergistic pathways involved in the development of altered health conditions, and molecular understanding of particular health condition. The differences of the detected metabolic profile of ischemic patients with or without previous myocardial infarction appear to be minor. This relatively inexpensive, non-invasive and reproducible approach may be useful for the molecular understanding and early prevention of IHD, improvement of surveillance and therapy. The study emerges the need for future investigations using larger cohort and possible longitudinal sight.

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Acknowledgements

This work was supported by the FP7 Bio-NMR program, European Regional Development Fund and European Social Fund’s Doctoral Studies and Internationalisation Programme DoRa and the Estonian Research Council Grant PUT 1534. Thanks to the Bio-NMR program for funding access to the Biomolecular NMR facility of the University of Birmingham.

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Correspondence to Tiina Titma.

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Titma, T., Shin, M., Ludwig, C. et al. The Metabolic Profile of Stable Ischemic Heart Disease by Serum 1H NMR. Appl Magn Reson 50, 527–539 (2019). https://doi.org/10.1007/s00723-018-1084-0

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