Serum levels of NLRP1, NLRP3, and HMGB1 in acute coronary syndrome patients and their prognostic significance

This study was designed to evaluate the circulating levels of pyroptosis-associated biomarkers, including NOD-like receptor family pyrin domain-containing protein 1 (NLRP1), NLRP3, and high mobility group box 1 (HMGB1), in patients with acute coronary syndrome, and to determine their clinical relevance and prognostic implications. We analyzed an expanded cohort of 335 patients with acute coronary syndrome (unstable angina (UA), ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI)) who were treated in our hospital from March 2020 to July 2025. Serum NLRP1, NLRP3, HMGB1, interleukin (IL)-6, IL-1β, and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Demographic and clinical data were recorded. All patients were followed for 12 months, and those who experienced major adverse cardiovascular events (MACE) were classified into the poor prognosis group. Multivariable logistic regression, ROC curve comparison, calibration, and incremental model analyses were performed. Serum NLRP1, NLRP3, and HMGB1 levels were significantly higher in the poor prognosis group. In multivariable analysis, NLRP1 (OR = 6.023, 95%CI 3.366–10.777), NLRP3 (OR = 4.532, 95%CI 2.680–7.666), and HMGB1 (OR = 2.041, 95%CI 1.264–3.296) were independently associated with 12-month MACE per 1-SD increase. NLRP3 had the numerically highest AUC (0.817, 95%CI 0.767–0.867), although it did not differ significantly from NLRP1 (AUC = 0.799, p = 0.635). In this derivation cohort, adding the three biomarkers to the study-specific reference model increased the AUC from 0.856 to 0.958 ( p < 0.001). Higher serum NLRP1, NLRP3, and HMGB1 levels were associated with poor 12-month prognosis in patients with acute coronary syndrome and provided incremental prognostic information relative to the study-specific reference model in this derivation cohort. These findings are hypothesis-generating and require independent external validation before clinical application.