Disruption of the tricarboxylic acid (TCA) cycle has been implicated in ischemic mitochondrial stress in acute myocardial infarction (AMI), yet its clinical prognostic utility remains uncertain. This prospective hospital-based cohort study published in BMC Medicine developed a composite TCA index and assessed its association with long-term outcomes, as well as its incremental prognostic value beyond established risk models.

A total of 4,071 AMI patients enrolled between February 2017 and June 2019 were analyzed. Plasma TCA metabolites were quantified using validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). The TCA index incorporated five intermediates: α-ketoglutarate, fumarate, methylmalonate, succinate, and malate. Multivariable Cox regression evaluated independent associations, and population attributable fractions (PAFs) were estimated. Incremental prognostic value beyond the Global Registry of Acute Coronary Events (GRACE) score and cardiac biomarkers was assessed using the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Over a median follow-up of 6.2 years, 1,263 (31.0%) major adverse cardiovascular events (MACE), 672 (16.5%) all-cause deaths, 373 (9.2%) cardiovascular deaths, and 561 (13.8%) heart failure (HF) events occurred. Each 1-standard deviation (SD) increase in the TCA index was independently associated with higher risk of MACE (hazard ratio [HR] 1.20; 95% confidence interval [CI] 1.13–1.27), cardiovascular death (HR 1.28; 95% CI 1.16–1.42), all-cause death (HR 1.22; 95% CI 1.13–1.32), and HF (HR 1.21; 95% CI 1.11–1.31). Addition of the TCA index to the GRACE score improved risk reclassification.

The TCA index was independently associated with adverse outcomes after AMI. It provided complementary prognostic information beyond established clinical models.