The Uremic Toxin p-Cresyl Sulfate Is a New Predictor of Major Adverse Cardiovascular Events in Patients with ST-Elevation Myocardial Infarction

ST-elevation myocardial infarction (STEMI) remains a major health concern despite advances in care. Indoxyl sulfate (IS) and p-cresyl-sulfate (p-CS) are gut-derived uremic toxins linked to higher morbidity and mortality in patients with chronic kidney disease (CKD). IS has been identified as an independent predictor of major adverse cardiovascular events (MACE) after STEMI, but data on p-CS are lacking. This study assessed the predictive value of IS and p-CS in STEMI patients with preserved renal function (cohort # NCT03070496). Plasma IS and p-CS were measured in 260 patients with STEMI who underwent primary coronary angiography. Samples collected 4 h after inclusion were analyzed using ultra-performance liquid chromatography with fluorescence detection. Optimal cut-offs were determined by the Youden index, and associations with MACE were evaluated by log-rank tests and Cox regression. Among 234 analyzed patients, 11.5% experienced MACE within one year. IS and p-CS levels were higher in the MACE group (IS: 3.14 vs. 2.19 µmol/L, <i>p</i> < 0.05; p-CS: 6.76 vs. 2.70 µmol/L, <i>p</i> < 0.01). Elevated p-CS independently predicted MACE (HR 3.79, 95% CI 1.29-11.17, <i>p</i> < 0.05), whereas IS lost significance after adjusting for kidney function. In STEMI patients, plasma p-CS is a stronger independent predictor of MACE than IS, highlighting its potential role in the gut-heart axis.