Comprehensive age-specific metabolic phenotyping in myocardial infarction

Aging is a main risk factor for the development of myocardial infarction (MI), with worse clinical outcomes. However, the understanding of age-related metabolic profiles in MI remains unclear. This study aimed to identify the clinical implications of age-specific metabolic phenotyping in the MI population. MI patients were classified into two categories as > 65 years ( n = 142) and ≤ 65 years ( n = 139). Comprehensive metabolic profiles, including hydrophilic and lipid metabolites, were quantified and compared in MI patients aged > 65 vs. ≤ 65 years. The primary clinical outcome was 3-year major adverse cardiac event (MACE), defined as the composite of cardiac death, non-fatal MI, and any revascularization. Overall, 88 aging-specific metabolites were identified in MI, specifying pathways of insulin resistance, lipolysis in adipocytes, and phenylalanine metabolism. Within the 3-year follow-up, 3-O-Methyldopa (3-OMD), Phenylacetyl-L-Glutamine (PAGln), Taurolithocholic acid (TLCA), and TG (10:0_16:0_18:1) were significantly associated with MACE. In multivariable analysis, 3-OMD (HR = 5.5, [95% CI 1.6–19.2], p = 0.007) and PAGln (HR = 3.8, [95% CI 1.3–11.4], p = 0.02) were the independent predictors of MACE. OCT examination was performed in the majority of MI patients (271/281, 96.4%); plaque rupture was diagnosed in 188 patients, and plaque erosion was identified in 77 patients. 3-OMD and PAGln were significant predictors of MACE in patients with plaque rupture but not in those with plaque erosion. In conclusion, in elderly MI patients, pathways of insulin resistance, lipolysis in adipocytes, and phenylalanine metabolism were activated. 3-OMD and PAGln indicate the poor clinical outcomes in MI patients with plaque rupture. Central illustration. Diagram of this study. In the upper panel, comprehensive metabolomics shows that 88 differential metabolites were found between elder and young MI individuals, among which 3-OMD, PAGln, TLCA and TG (10:0_16:0_18:1) were associated with MACE. In the lower panel, the two independent predictive biomarkers of 3-OMD and PAGln were significantly associated with age and clinical outcomes in MI patients caused by plaque rupture. In contrast, negative results were observed in MI patients caused by plaque erosion.