Abstract
Introduction: Mental stress-induced myocardial ischemia (MSI) is a marker of future cardiovascular events. The underlying biochemical mechanisms of this cardiovascular condition are poorly understood. Our objective was to use metabolic profiling to identify biochemical changes associated with mental stress (MS) in patients with stable coronary artery disease (CAD) and investigate differential pathways that are involved in MSI. Methods: A total of 110 Individuals with stable CAD who participated in the Mental Stress Ischemia Prognosis Study (MIPS) underwent a standardized mental stress to provoke of myocardial ischemia, detected with single-photon emission tomography. Plasma samples were obtained before and after MS at 45 and 90 minutes and metabolomic profiling was performed using liquid chromatography/mass spectrometry using a confirmed 500 compounds. Metabolomic features and pathways associated with ischemia using metabolome-wide association studies and Mummichog, respectively. Results: The sample involved a subset case-control for (MSI+ vs MSI-). At 45 minutes and 90 minutes, there were significant stress-induced changes in several compounds. There was a significant upregulation of metabolites associated with lipid signaling et ( p = 0.025, Inosine diphosphate). A comparison between the MSI+ and MS- groups showed differential upregulation of DNA methylation metabolites ( p = .036, 5-Methylcytosine hydrochloride) at 45 minutes and microbiome-related metabolites at 90 minutes (P=0.041, N, N-dimethyl-1,4-phenylenediamine). Pathway analyses were consistent with the aforementioned findings. Conclusion: Upregulation of metabolic pathways involved in DNA methylation and microbial metabolism is differentially associated with MSI. These findings provide novel mechanistic insights into the association between acute mental stress and myocardial ischemia as a marker for cardiovascular vulnerability in patients with CAD
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