Thromboinflammation is associated with clinical outcome after ST-elevation myocardial infarction

• Thromboinflammatory marker H3Cit-DNA is enhanced in STEMI.

• It is associated with clinical outcome and identifies patients at high risk of MACE.

Platelets are crucial in thrombus formation during ST-elevation myocardial infarction (STEMI). In addition, they also play an important role in post-ischemic thromboinflammation which is determined by the interplay between activated platelets and neutrophils. The latter form neutrophil extracellular traps (NETs) which are detectable in plasma as citrullinated histone H3 - DNA complexes. Prediction of risk of recurrent events is important in precision medicine. Therefore, we investigated if circulating thromboinflammatory markers predict clinical outcome after STEMI. We performed a prospective, multicentric, observational, all-comer study of STEMI patients (n=361). Thromboinflammation, measured as H3Cit-DNA complexes, was assessed on day one after presentation with STEMI as well as five days and six months after STEMI by ELISA. Twelve months clinical follow-up was conducted. Multivariate analysis was performed investigating which variables were independently associated with major adverse cardiac events (MACE). Patients were 64 ± 12 years old, 80 % male and 40 % had diabetes mellitus. Thromboinflammation was enhanced during index hospitalization as compared to six months follow-up (137.4 ± 100.0 µg/l vs. 53.7 ± 54.7 µg/l, p<0.001). Additionally, patients within the highest tertile of thromboinflammation at day one after STEMI showed worse outcome during follow-up (HR 2.57, CI 1.72-3.85, p<0.001). Receiver operating characteristics (ROC) analysis revealed a cut-off value of 219.3 µg/l. In multivariate logistic regression analysis, thromboinflammation was independently associated with outcome after STEMI. To sum it up, thromboinflammation is enhanced in STEMI. It identifies patients at high risk of MACE. Therefore, thromboinflammation might be a promising target and marker in precision medicine. Trial Registration Number: NCT03539133