Complement activation in association with clinical outcomes in ST-elevation myocardial infarction

Area of Science:

• Cardiology
• Immunology
• Biochemistry

Background:

• Complement system activation and neutrophil extracellular traps (NETs) are implicated in ischemia-reperfusion injury during ST-elevation myocardial infarction (STEMI).
• Understanding the prognostic value of these pathways in STEMI patients is crucial for risk stratification and management.

Purpose of the Study:

• To investigate the association between complement activation, specifically the terminal complement complex (TCC), and NETs in STEMI patients.
• To evaluate the prognostic significance of TCC and NETs on clinical endpoints, including a composite endpoint and total mortality.

Main Methods:

• A cohort study included 864 STEMI patients undergoing percutaneous coronary intervention (PCI).
• Terminal complement complex (TCC) levels were measured, alongside NET markers (myeloperoxidase-DNA, citrullinated histone 3, dsDNA).
• Cox regression and ROC curve analysis were used to assess associations with clinical endpoints over a median follow-up of 4.6 years.

Main Results:

• TCC showed weak correlations with dsDNA and citrullinated histone 3.
• TCC was not associated with the composite endpoint but showed a trend towards association with total mortality (p=0.044), which was lost after adjusting for clinical factors.
• Receiver operating characteristic (ROC) curve analysis indicated that dsDNA alone had better prognostic value for total mortality than TCC alone, and combining TCC with dsDNA did not significantly improve this value.

Conclusions:

• In STEMI patients, TCC did not demonstrate significant prognostic value for the composite endpoint and showed limited association with total mortality.
• dsDNA, a marker of NETs, offered better prognostic capability for total mortality compared to TCC.
• Combined assessment of TCC and dsDNA did not enhance prognostic prediction beyond dsDNA alone in this STEMI cohort.