Platelet-derived Let-7e is an Independent Predictor of Long-term All-cause Mortality in Patients with Type 2 Diabetes Mellitus

C. Eyileten¹, J. Pordzik¹, D. Jakubik¹, P. Czajka¹, M. Wolska¹, J. Jarosz-Popek^1,2, A. Fitas¹, A. Nowak¹, S. De Rosa³, A. Gąsecka⁴, A. Kapłon-Cieślicka⁴, J.M. Siller-Matula⁵, M. Postuła¹

¹Center for Preclinical Research and Technology CEPT, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland, ²Doctoral School, Medical University of Warsaw, Warsaw, Poland, ³Division of Cardiology, Department of Medical and Surgical Sciences, 'Magna Graecia' University, Catanzaro, Italy, ⁴1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland, ⁵Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

Abstract Number: PB0011

Meeting: ISTH 2021 Congress

Theme: Arterial Thromboembolism » Cardiovascular Risk Factors

Background: In the light of growing prevalence of type 2 diabetes mellitus (T2DM), efforts are made to discover novel biomarkers. MicroRNAs (miRNAs-miR) are non-coding RNAs used in various processes involved in regulating gene expression which play a role in platelet function.

Aims: To analyze the ability of platelet-derived miRNAs in prediction of mortality and response to antiplatelet treatment among T2DM-patients.

Methods: 252 diabetic subjects were enrolled and were receiving either acetylsalicylic acid (ASA) 75mg (65%) or 150 mg (15%) or clopidogrel (19%). Plasma miR-126, miR-223, miR-125a-3p and Let-7e expressions were assessed by qRT-PCR and compared between the patients who survived and those who died. Median observation time was 5.9 years. Adjusted Cox-regression analysis was used for prediction of mortality. Differential miRNAs expression due to different antiplatelet treatment was analyzed.

Results:

ROC curve analysis revealed increasing concentrations of miR-126, Let-7e and miR-125a-3p levels had a diagnostic ability for prediction of long-term all-cause mortality (c-index=0.75, p<0.001; 0.72, p<0.001; 0.72, p=0.001, respectively). Multivariate Cox regression model revealed high miR-126 and Let-7e expressions which were strong and independent predictors of all-cause long-term mortality (HR=5.08, 95% CI: 1.92-13.43; p=0.001; HR=5.94, 95% CI:1.98-17.79; p=0.001,respectively). After including all miRNAs into one multivariate Cox regression model, only Let-7e was predictive of future occurrence of long-term all-cause death (HR=7.83, 95% CI: 1.2-51.1; p=0.032). MiR-126, Let-7e and miR-223 expressions in the clopidogrel group were significantly higher than in the ASA group (p=0.014; p=0.013; p=0.028, respectively).

MiRNAs expressions in regard to the type of antiplatelet treatment based on randomization [ASA 75 mg vs ASA 150 mg vs Clopidogrel]; a) miR-126; b) Let-7e; c) miR-223; d) miR-125a-3p.

Multivariate Cox regression model including high levels of miRNAs and clinical data

Conclusions: Let-7e expression is a strong and independent predictor of long-term all-cause mortality among patients with T2DM. MiR-223, miR-126 and Let-7e present significant interactions with antiplatelet treatment and clinical outcomes.

To cite this abstract in AMA style:

Eyileten C, Pordzik J, Jakubik D, Czajka P, Wolska M, Jarosz-Popek J, Fitas A, Nowak A, De Rosa S, Gąsecka A, Kapłon-Cieślicka A, Siller-Matula JM, Postuła M. Platelet-derived Let-7e is an Independent Predictor of Long-term All-cause Mortality in Patients with Type 2 Diabetes Mellitus [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/platelet-derived-let-7e-is-an-independent-predictor-of-long-term-all-cause-mortality-in-patients-with-type-2-diabetes-mellitus/. Accessed November 28, 2023.

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