Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation
Ana Blasco1,2, Axel Rosell3,4, Raquel Castejón5
1Cardiology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
Insights
Neutrophil extracellular trap (NET) marker nucleosomal citrullinated histone H3 (H3Cit-DNA) did not predict adverse events in ST-elevation myocardial infarction (STEMI) patients. Classical inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) improved 30-day risk prediction.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Biomarker Discovery
Background:
- Inflammation is central to ST-elevation myocardial infarction (STEMI) pathophysiology.
- Neutrophil extracellular traps (NETs) and their components are implicated in STEMI prognosis.
- The prognostic value of specific circulating NET markers remains unclear.
Purpose of the Study:
- To evaluate nucleosomal citrullinated histone H3 (H3Cit-DNA), a NET-specific marker, for predicting adverse events post-STEMI.
- To compare the predictive utility of H3Cit-DNA with classical inflammatory markers.
Main Methods:
- Retrospective cohort study of 487 STEMI patients undergoing primary percutaneous coronary intervention (PCI).
- Analysis of serum H3Cit-DNA, double-stranded DNA, IL-6, IL-1β, TNF-α, and CRP levels on admission.
- Association with major adverse cardiovascular events (MACE) including death, reinfarction, urgent revascularization, and heart failure.
Main Results:
- H3Cit-DNA levels were not associated with 30-day mortality, MACE, Killip class, or left ventricular ejection fraction.
- C-reactive protein (CRP) and interleukin-6 (IL-6) levels significantly improved the prediction of 30-day MACE when added to a clinical risk model.
Conclusions:
- Circulating H3Cit-DNA is not a useful predictor of cardiovascular events in the early stages of STEMI.
- Classical inflammatory markers CRP and IL-6 demonstrate significant prognostic value in STEMI.
- NET-specific markers may have limited utility for assessing early inflammatory states in STEMI.
Background And Aims:
Inflammation plays a pivotal role in the pathophysiology of ST-elevation myocardial infarction (STEMI). This involves neutrophil activation and the local release of pro-inflammatory mediators. The formation of neutrophil extracellular traps (NETs) in coronary thrombosis has been linked to poor short-term prognosis following STEMI, but the usefulness of specific circulating NET components as prognostic markers is unclear. We aimed to evaluate the NET-specific marker nucleosomal citrullinated histone H3 (H3Cit-DNA) and other classical inflammatory markers to predict adverse events after STEMI.
Methods:
This is a single-center retrospective cohort study of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) from 2015 to 2019. We analyzed the association between serum H3Cit-DNA levels, double-stranded DNA, and classical inflammatory markers -such us interleukin (IL) 6 and 1β, TNF-α, and C-reactive protein (CRP)- on admission and the occurrence of major cardiovascular events (MACE), including death, reinfarction, urgent revascularization, or heart failure, after STEMI.
Results:
A total of 487 patients were studied, of which 380 were men [78%]; mean [SD] age of patients was 63 [13] years, and median [95%CI] follow-up was 5.4 [5.2-5.5] years. Median [IQR] H3Cit level was 179.30 [105.30-281.47] ng/ml. No relevant association was found between H3Cit-DNA levels and 30-day mortality (OR, 1.03 [95%CI, 0.71-1.50], p = 0.861) or MACE (0.98 [0.72-1.32], p = 0.879), Killip class (0.95 [0.74-1.21], p = 0.664), or left ventricular ejection fraction (ref.cat. > 50%; < 35%, RRR 1.01 [95%CI, 0.74-1.38], p = 0.952; 35-50%, 1.26 [1.07-1.48], p = 0.005]. Adding CRP and IL-6 levels as covariates to a model based on classical risk factors significantly improved the prediction of MACE at 30 days after STEMI (IDI 0.13; NRI 0.32, p < 0.05).
Conclusions:
Circulating levels of the NET marker H3Cit-DNA at the time of primary PCI were not predictive of cardiovascular events following STEMI. In contrast, the classical inflammatory markers CRP and interleukin-6 significantly enhanced the discriminative capacity of a clinical 30-day risk prediction model. These findings suggest that measuring circulating NET-specific markers may have limited utility in assessing the inflammatory state during the early stages of STEMI.
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