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High Concentration of Symmetric Dimethylarginine is Associated with Low Platelet Reactivity and Increased Bleeding Risk in Patients with Acute Coronary Syndrome

C. Eyileten1, J. Jarosz-Popek1,2, D. Jakubik1, A. Gąsecka3, M. Wolska1, A. Fitas1, P. Czajka1, A. Nowak1, M. Ufnal4, M. Postuła1, J.M. Siller-Matuła5,1

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, 31st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland, 4Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland, 5Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria

Abstract Number: PB0001

Meeting: ISTH 2021 Congress

Theme: Arterial Thromboembolism » Acute Coronary Syndromes

Background: One of the promising biomarkers in CVD are asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), which are products of L-arginine methylation and are both involved in endothelial dysfunction. ADMA, SDMA and L-homoarginine, have emerged as biomarkers linked to cardiovascular outcomes.

Aims: To investigate the association of SDMA with platelet reactivity and bleeding risk in patients with acute coronary syndrome (ACS) treated with potent P2Y12 inhibitors prasugrel and ticagrelor.

Methods: Our prospective observational study enrolled 292 patients. Plasma concentrations of SDMA were measured during the hospitalization for ACS. Impedance aggregometry was used. The primary study endpoint was the concentration of metabolites and platelet reactivity.

Results: There was an inverse correlation between SDMA serum levels and platelet reactivity (r = -0.25; p< 0.000). The ADP+PGE1-induced platelet reactivity was 33% lower among patients with the highest SDMA quartile (4th) as compared to those with the 1-3rd SDMA quartile (8 [0-29] vs 12 [0-126] U; p< 0.001). The AA-induced platelet reactivity was 56% lower among patients with the highest SDMA quartile (4th) as compared to those with the 1-3rd SDMA quartile (4 [0-48] vs 9 [0-133]; p<0.001). In a multivariate model, the highest SDMA (4th) quartile was found to be an independent predictor of the lowest ADP+PGE1 and AA induced platelet aggregation (OR: 2.666, 95% CI [1.184–5.999], p = 0.018).


Platelet reactivity as assessed with the Multiple Aggregometry (MEA) for comparison between plasma SDMA quartiles. a) ADP+PGE1-induced platelet aggregation, b) Arachidonic acid (AA)-induced platelet aggregation. c) Distribution of plasma SDMA concentration across patients with and without TIMI bleeding events during 12 months of DAPT treatment. SDMA concentration differed among the four groups (p=0.040, Kruskal –Wallis’ test). SDMA concentration in the TIMI major group was higher than that in the TIMI minimal group significantly (p=0.043, Mann-Whitney’s U test).

Multivariate logistic regression analysis of factors which correlates with lowest platelet reactivity (lowest quartile of AA and ADP+PGE1- induced platelet aggregation)

Conclusions: Our study shows that high plasma concentration of SDMA, but not ADMA, is independently associated with low platelet reactivity to ADP and AA and is associated with  major and minor bleeding events in patients with ACS on potent antiplatelet therapies. Therefore, SDMA might have a potential to be further evaluated as a blood biomarker for individualization of duration and potency of antiplatelet therapies in an ACS population at high risk of bleeding complications.

To cite this abstract in AMA style:

Eyileten C, Jarosz-Popek J, Jakubik D, Gąsecka A, Wolska M, Fitas A, Czajka P, Nowak A, Ufnal M, Postuła M, Siller-Matuła JM. High Concentration of Symmetric Dimethylarginine is Associated with Low Platelet Reactivity and Increased Bleeding Risk in Patients with Acute Coronary Syndrome [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/high-concentration-of-symmetric-dimethylarginine-is-associated-with-low-platelet-reactivity-and-increased-bleeding-risk-in-patients-with-acute-coronary-syndrome/. Accessed October 1, 2023.

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