To our knowledge, this is the first assessment of the predictive value of EOS% on AAAD mortality. Here, we find that: (1) relative to surviving patients, those that died had lower EOS% level and higher WBC and neutrophil counts, (2) despite adjustment for potential confounders, low EOS% was a significant predictor of mortality, (3) Eosinophils accumulated in the aortic dissection thrombus.
Eosinopenia, first described by Bass et al. in 1980 , refers to marked reduction in the number of circulating eosinophils during acute infection. Eosinophils were subsequently shown to be associated with mortality in critically ill patients . Recently study reported that the relevance of eosinopenia and unfavorable outcomes in patients with acute ischemic stroke . A retrospective study on 606 STEMI patients for 3.5 years suggested that eosinopenia indicates poor cardiac outcomes . Currently, no published studies have evaluated the association between eosinophils and AD and to our knowledge, ours is the first to show that decreased EOS% levels were correlated with in-hospital and 1-year AAAD mortality. Reduced circulating eosinophils increased in-hospital and 1-year mortality by 3-5 and 2-3 fold, respectively. This finding was independently verified on the MIMIC IV database, which is comprised of totally different demographic features.
Past studies have associated WBCs and neutrophils, important inflammatory markers, with unfavorable AAAD outcomes[5, 16]. Our data show that EOS% negatively correlates with WBC and neutrophil levels, suggesting that there is severe inflammatory reaction when EOS% decreases. In AD, inflammatory reactions underlie aortic rupture . Here, multivariate regression analysis displayed reduced EOS% as a vital predictor of AAAD mortality even after adjusting for WBC and neutrophil levels. Moreover, we find that all thrombus samples contain eosinophils, suggesting that eosinophils contribute to thrombus formation and development in AD. This is similar to a previous study by Riegger et al. that eosinophils are present in all stent thrombosis . EOS% seems to be a more suitable predictor of adverse outcome for AAAD patients because it simultaneously represents inflammation and thrombosis.
The mechanisms underlying the association between eosinopenia and poor AAAD prognosis is unclear. There are several potential reasons for the sharp eosinophils decrease in peripheral blood. AAAD, which is associated with severe pain, can evoke acute stress responses that stimulate the release of glucocorticoids like cortisol , leading to eosinopenia via apoptosis [18–19]. Another major reason is that cytokine- and chemokine-mediated eosinophils accumulation at injury sites may reduce circulating eosinophils [20–21]. Aggregated eosinophils involved in development and progression of aortic dissection by regulating inflammatory response and thrombosis. Eosinophils are capable to express tissue factor  and produce procoagulant phospholipid surface, which activate prothrombinase complex to generate thrombin, further promoting fibrin formation [23–24]. Besides, eosinophils interact with platelets at the lesion site leading to mutual activation. Eosinophils migrate into the thrombi and are activated by platelets, thereby promoting the formation of eosinophil extracellular traps (EETs). EETs, which contain major basic protein (MBP), lead to platelet activation by eosinophils. Activated platelets, EETs, and MBP contribute to thrombus formation [25–26]. Besides, eosinophil granules also contain MBP, eosinophil peroxidase (EPO), and eosinophil cationic protein, which cause tissue damage and inflammation . Eosinophils are pro-inflammatory cells and can release a great number of chemokines, cytokines, and growth factors, which enhance inflammatory reactions [21, 28]. It is reported that inflammation influences AD occurrence and development . Cytokines, including interleukin (IL)-1β, IL-2, IL-6, IL-8, and tumor necrosis factor-α, are upregulated in AD patients [30–33], and may promote AD via apoptosis [33–35]. Eosinophils also express transforming growth factor-β, which is elevated in AD and associated with an upregulation of matrix metalloproteinases [37–38]. Both are implicated in the vascular remodeling via collagen and extracellular matrix degradation [29, 39]. Eosinophils release chemokines like CXC-motif chemokine ligand 8/IL-8, which can recruit leukocytes to the site of inflammation .
Some potential limitations should be taken into consideration. Firstly, due to its small sample size and retrospective nature, some bias is inevitable. Secondly, we only confirmed eosinophil presence in AD thrombosis but did not determine how eosinophils promote AD development. Thus, further investigations are warranted to determine the role of eosinophils in AD development.