Complement activation in association with clinical outcomes in ST-elevation myocardial infarction
Karsten E Kluge1,2, Miriam S Langseth1,2, Geir Ø Andersen1,3
1Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Norway.
Insights
Terminal complement complex (TCC) showed a weak association with total mortality in ST-elevation myocardial infarction (STEMI) patients. Combining TCC with dsDNA did not improve prognostic value over dsDNA alone for predicting adverse outcomes.
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.
Introduction:
The complement system and neutrophil extracellular traps (NETs) might contribute to ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI). We aimed to estimate associations between complement activation and NETs in STEMI, and their prognostic value on clinical endpoints.
Methods:
In this cohort study, 864 patients admitted for PCI during STEMI were included. Complement activation was analyzed by the terminal complement complex (TCC), while NETs were analyzed by myeloperoxidase-DNA, citrullinated histone 3 (CitH3) and dsDNA. The composite endpoint was reinfarction, unscheduled revascularization, stroke, hospitalization due to heart failure, or death, and the secondary endpoint was total mortality. The association between TCC and clinical endpoints was assessed by Cox regression and ROC curve analysis.
Results:
TCC was weakly correlated to dsDNA (r = 0.127, p < 0.001) and CitH3 (r = 0.102, p = 0.003). After a median follow-up time of 4.6 years, 184 (21.3 %) patients had reached a clinical endpoint. TCC was not associated with the composite endpoint, but with total mortality (HR: 1.673, 95 % CI: [1.014, 2.761], p = 0.044). The significant association was lost when adjusting for CRP, NT-proBNP, LVEF and time from symptoms to PCI. In ROC curve analysis of total mortality, the AUC for TCC alone was 0.549 (95 % CI: [0.472, 0.625]), AUC for dsDNA alone was 0.653 (95 % CI: [0.579, 0.720]), while AUC for TCC and dsDNA combined was 0.660 (95 % CI: [0.590, 0.730]).
Conclusions:
In this STEMI cohort, TCC was not associated with the composite endpoint, but somewhat with total mortality. Combining TCC and dsDNA did not increase the prognostic value compared to dsDNA alone.
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