MiR-223 levels predicting perioperative bleeding in off-pump coronary artery bypass grafting

Abstract

Background: To investigate the predictive value of platelet-related microRNAs (miRNAs) for bleeding during and after off-pump coronary artery bypass grafting (OPCABG) and the influence of dual antiplatelet therapy (DAPT) on miRNAs.Methods: This prospective study included 59 patients scheduled for OPCABG. The plasma miR-126 and miR-223 levels were measured and platelet aggregation was determined by thromboelastography during DAPT. The plasma miRNA levels were compared between patients treated with ticagrelor or clopidogrel. Multivariable logistic regression analysis was performed to determine the independent risk factors for bleeding during and after surgery. Active bleeding was defined as a blood loss >1.5 mL/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation during the first 12 postoperative hours. Severe perioperative bleeding was defined using the universal definition of perioperative bleeding in adult cardiac surgery. Results: Higher circulating miR-223 levels [odds ratio (OR) =1.348, 95% confidence interval (CI): 1.001-1.814, P=0.047] and lower body mass index (OR =0.648, 95% CI: 0.428-0.980, P=0.040) were independent predictors for severe perioperative bleeding in OPCABG. Ticagrelor treatment led to significant increases in circulating miR-223 levels compared with clopidogrel treatment. Conclusions: The plasma miR-223 levels served as a predictor for bleeding during and after OPCABG. Circulating miR-223 levels were significantly elevated with ticagrelor treatment compared with clopidogrel treatment. MiR-223 may be a novel biomarker for bleeding in cardiac surgery and can help explain the different efficacies of ticagrelor and clopidogrel.

MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review

“…High expression of miR-223 was found to serve as a potential independent predictive marker of perioperative bleeding in off-pump coronary artery bypass surgery. The levels of this miRNA were significantly higher in patients treated with DAPT consisting of ASA and ticagrelor when compared to those treated with ASA and clopidogrel (Wang et al, 2020). Not only miR-223, but also miR-150, miR-21, and miR-126 expressions during DAPT were strongly correlated with the type of administered P2Y 12 receptor inhibitor.…”

Diagnostic and Prognostic Value of miRNAs after Coronary Artery Bypass Grafting: A Review

“…Through upregulation of miR-126, the production of platelet-derived VEGF-A decreased, which provided protection from by-pass closure [ 91 ]. Platelet-derived MiR-223, in turn, could serve as a predictor for bleeding during and after off-pump CABG surgery [ 156 ].…”

MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

“…We aimed to determine the prognostic performance of selected circulating miRNAs for all-cause mortality and their potential usefulness as biomarkers in T2DM patients on antiplatelet treatment. Several studies showed the role of miR-126 and miR-223 in the context of antiplatelet treatment in many different cohorts [ 16 , 19 , 20 , 21 , 22 , 23 ]. Changes in plasma miRNAs in response to antiplatelet therapy were investigated in a small cohort of healthy volunteers [ 16 , 19 , 20 , 21 , 22 , 23 ].…”

“…Yu et al analyzed the correlation between plasma miR-126 and miR-223, among others, and the risk of major adverse cardiovascular events in patients on dual antiplatelet therapy (DAPT) after percutaneous coronary intervention [ 16 , 19 , 20 , 21 , 22 , 23 ]. The association between miRNAs and platelet reactivity was also studied in patients with acute coronary syndrome (ACS) on various antiplatelet therapies [ 16 , 19 , 20 , 21 , 22 , 23 ]. In a similar study Carino et al assessed miR-126 and miR-223, among other miRNAs, in patients with ACS before and after the therapeutic switch from DAPT to ticagrelor [ 16 , 19 , 20 , 21 , 22 , 23 ].…”

“…In a similar study Carino et al assessed miR-126 and miR-223, among other miRNAs, in patients with ACS before and after the therapeutic switch from DAPT to ticagrelor [ 16 , 19 , 20 , 21 , 22 , 23 ]. More recently the association of platelet-related miRNAs was studied in ACS patients on DAPT and pathophysiological processes in the TDM population [ 16 , 19 , 20 , 21 , 22 , 23 ]. Among others, Let-7e and miR-125a-3p are molecules that have been formerly linked to inflammation, platelet reactivity, and mechanisms leading to diabetes; however, the impact of antiplatelet therapy on Let-7e and miR-125a-3p and their prognostic potential has not been studied so far [ 24 , 25 , 26 ].…”