Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation: Comment from Luo et al.

Abstract

In this interesting paper, the authors revealed that nine out of 268 investigated biomarkers were significantly and independently associated with the risk of bleeding and reflect pathophysiologic processes of inflammation, apoptosis, oxidative stress, vascular calcification, coagulation, and fibrinolysis. 1 Recent studies have shown that accurate assessment to balance the risk of stroke and systemic embolic events, against the risk of major bleeding is, therefore, an important therapeutic goal in the clinical management of atrial fibrillation (AF) patients. 2 Although the results showed a strong correlation between the TRAIL-R2 protein marker and the risk of bleeding, the potential mechanistic remain to be elucidated. It is known that TRAIL-R2 is a marker of apoptosis and belongs to the tumor necrosis factor receptor superfamily. 3,4 However, a recent study by Tymon Pol et al. 4 published on Cardiovascular Research proposed TRAIL-R2 is not specific for AF but rather a marker that rises in several disease states just indicating poor prognosis. Meanwhile, Isabel Gonçalves et al. 5 showed that sTRAIL-R2 and sTRAIL are associated with human plaque cell apoptosis, plaque inflammatory activity, and symptomatic carotid plaques, especially for high plasma levels of sTRAIL-R2 in plasma predict, independently, future cardiovascular events in individuals. Thus, it is unclear whether the strong correlation between the increased level of TRAIL-R2 and the risk of bleeding uncovered in Agneta Siegbahn's study is confounded by other unknown factors. We speculate that the potential mechanism is that TRAIL-R2 induces the inflammatory activity of cells, leading to inflammatory injury of endothelial cells and apoptosis of the vascular wall. 1,5 Taken together, we can reasonably speculate that TRAIL-R2 may be a biomarker and contribute to predicting future cardiovascular events in AF patients by affecting the risk of bleeding. Clearly, a great number of research opportunities could be further explored following Agneta Siegbahn's interesting study.Despite some limitations, the work by authors not only provides novel candidate biomarkers associated with major bleeding for AF but also opens a new avenue to future basic and clinical studies in AF.