Synergistic role of circulating CD14++CD16+ monocytes and fibrinogen in predicting the cardiovascular events after myocardial infarction

Background: Monocytes and fibrinogen (FIB) play important roles in driving acute and reparative inflammatory pathways after myocardial infarction (MI). In humans, there are three subsets of monocytes, namely, CD14++CD16- (Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). During the inflammatory response, monocyte subsets express high levels of integrin α_M β₂ and protease-activated receptors 1 and 3 to interact with FIB.

Hypothesis: However, whether there is a synergistic role of FIB combined with Mon2 counts in prioritizing patients at high risk of future major adverse cardiovascular events (MACEs) after MI remains unknown.

Methods: The MI patients who treated with primary percutaneous coronary intervention were enrolled. MI patients were categorized into four groups, that is, low FIB/low Mon2, low FIB/high Mon2, high FIB/low Mon2, and high FIB/high Mon2, according to cutoff values of 3.28 g/L for FIB and 32.20 cells/μL for Mon2. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the risk of MACEs of MI patients during a median follow-up of 2.7 years. Mediating effects of high FIB levels and MACEs associated with high monocyte subsets were calculated by mediation analysis.

Results: High FIB/high Mon2 group had the highest risk of MACEs during a median follow-up of 2.7 years. Moreover, mediation analysis showed that a high FIB level could explain 24.9% (p < .05) of the increased risk of MACEs associated with Mon2.

Conclusion: This work provides evidence indicating the translational potential of a synergistic role of FIB combined with Mon2 in prioritizing patients at high risk of future MACEs after MI.