Circulating Markers of Neutrophil Extracellular Traps for Long-Term Prognosis in Patients With Acute Chest Pain

Neutrophil extracellular traps are released from activated neutrophils and are involved in the pathogenesis of atherosclerotic lesions, atherothrombosis, and myocardial injury. We investigated the prognostic value of circulating neutrophil extracellular trap biomarkers in patients with suspected acute coronary syndrome (ACS).

A total of 1482 patients admitted with suspected non-ST-segment elevation ACS were included and followed for a median of 4.2 years. The primary end point was a composite of death from any cause, incident myocardial infarction and hospitalization for heart failure. Secondary end points were all-cause mortality, cardiovascular death, incident myocardial infarction, hospitalization for heart failure, and new-onset atrial fibrillation. Admission blood samples were analyzed for the neutrophil extracellular trap biomarkers double-stranded DNA (dsDNA), CitH3 (citrullinated histone H3), and myeloperoxidase-DNA.

A doubling of dsDNA concentration was associated with a hazard ratio (HR) of 3.11 (95% CI, 1.61-5.98, P<0.001) for the primary end point after adjusting for traditional risk factors, cardiac troponin T and N-terminal pro-B-type natriuretic peptide. DsDNA served as a prognostic marker both in patients with (adjusted HR, 5.33 [95% CI, 1.67-17.06], P=0.005) and without ACS (adjusted HR, 2.86 [95% CI, 1.30-6.28], P=0.009). In contrast, CitH3 and myeloperoxidase-DNA showed no significant prognostic value.

In patients with suspected ACS, dsDNA emerged as a long-term prognostic marker for a composite outcome of death, incident myocardial infarction, or heart failure hospitalization, independent of conventional risk factors. DsDNA can independently from established risk factors identify high-risk patients with and without ACS who may benefit from risk reduction.