Key result
High admission citrullinated histone H3 linked to ~114% greater MACE risk after STEMI.
Why the study?
Do elevated circulating NETosis biomarkers (H3Cit, cfDNA, nucleosomes) at admission predict MACE and death in STEMI patients after primary PCI?
Cohort (n=420)
Yes
Do elevated circulating NETosis biomarkers (H3Cit, cfDNA, nucleosomes) at admission predict MACE and death in STEMI patients after primary PCI?
Hazard Ratio: 2.139 (95% CI 1.313–3.486)
Absolute Event Rate: 35.6% vs 16.3%
p-value: p=0.002
Circulating citrullinated histone H3 (H3Cit) measured at admission provides strong, independent prognostic information for MACE and death in STEMI patients after primary PCI, outperforming cfDNA and nucleosomes.
Admission H3Cit may refine post-STEMI risk stratification; leaves open whether NETosis markers warrant prospective validation before clinical use.
Background: Even after successful primary percutaneous coronary intervention (PPCI), a substantial proportion of ST-elevation myocardial infarction (STEMI) patients develop major adverse cardiovascular events (MACE). Neutrophil extracellular trap formation (NETosis) contributes to atherothrombosis and coronary microvascular injury, but the prognostic value of circulating NETosis biomarkers in STEMI has not been systematically compared. Methods: We studied 420 STEMI patients who survived index hospitalisation after PPCI. Plasma citrullinated histone H3 (H3Cit), cell-free DNA (cfDNA) and nucleosomes were measured at admission. The primary endpoint was MACE; all-cause death was secondary. Incremental prognostic value over a conventional model was assessed by ΔC-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: Over a median 545-day follow-up, 81 patients (19.3%) experienced MACE and 36 (8.6%) died. In fully adjusted Cox models, each 100ng/mL increase in H3Cit was independently associated with MACE (HR 1.511, 95% CI 1.155– 1.977, P=0.003) and death (HR 1.752, 95% CI 1.203– 2.552, P=0.003). Q4 vs Q1–Q3 H3Cit independently predicted MACE (HR 2.139, P=0.002) and death (HR 2.836, P=0.004). cfDNA was associated with death but not MACE after adjustment; nucleosomes lost significance after full adjustment. Adding H3Cit improved discrimination for MACE (ΔC-index 0.042; NRI 0.417; IDI 0.022) and death (ΔC-index 0.055). The prognostic association of H3Cit was directionally consistent across prespecified subgroups. Conclusion: Among three circulating NET biomarkers, H3Cit provides the strongest and most consistent prognostic information for MACE and death after STEMI and offers meaningful incremental value beyond established clinical risk factors, supporting NETosis as a potentially actionable pathway for post-STEMI risk stratification.
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Xin et al. (2026) conducted a cohort in ST-elevation myocardial infarction (STEMI) (n=420). Citrullinated histone H3 (H3Cit) vs. Lower quartiles (Q1-Q3) was evaluated on Major adverse cardiovascular events (MACE) (HR 2.139, 95% CI 1.313-3.486, p=0.002). Higher admission levels of citrullinated histone H3 (highest quartile vs lower quartiles) independently predicted an increased risk of major adverse cardiovascular events (HR 2.139) after STEMI.
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