Symmetric Dimethylarginine is Altered in Patients After Myocardial Infarction and Predicts Adverse Outcomes

Abstract

Aleksandra Gąsecka,1 Piotr Szwed,1 Karolina Jasińska,1 Oliwia Fidali,1 Aleksandra Kłębukowska,1 Ceren Eyileten,2 Marek Postula,2 Łukasz Szarpak,3,4 Tomasz Mazurek,1 Grzegorz Opolski,1 Krzysztof J Filipiak,1 Marcin Ufnal5 1 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, 02-097, Poland; 2Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, 02-097, Poland; 3Bialystok Oncology Center, Bialystok, 15-027, Poland; 4Maria Sklodowska-Curie Medical Academy in Warsaw, Warsaw, 03-411, Poland; 5Department of Experimental Physiology and Pathophysiology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, 02-106, PolandCorrespondence: Aleksandra Gąsecka 1st Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, Warsaw, 02-097, PolandTel [phone]Email [email protected]: Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. Damage to the endothelium is the earliest event in atherothrombosis, including AMI. Nitric oxide (NO), an endothelium-derived compound, protects the vasculature from damage. This study evaluated whether an association exists between plasma concentration of endogenous NO-related pathway metabolites linked to AMI and major adverse cardiovascular events (MACE) after AMI.Methods: We compared plasma concentrations of NO-related pathway metabolites in patients after AMI (n=60) and healthy controls (n=27) and investigated the prognostic value of these metabolites for post-AMI MACE development over a median of 3.5-years. In search of biomarkers, we compared plasma concentrations of dimethylarginines (ADMA, SDMA), citrulline, arginine and ornithine using ultra performance liquid chromatograph coupled with a mass spectrometer.Results: Patients after AMI had higher concentrations of dimethylarginines, compared to controls (p=0.0068, p< 0.0001, respectively). Conversely, the concentration of citrulline was lower in the AMI group (p=0.0006). The concentration of SDMA was higher in patients who developed MACE than in those who did not (p=0.015). SDMA was the only independent predictor of MACE in multivariate analysis (p=0.023). There was an intermediate, negative correlation between plasma SDMA level and platelet reactivity (r=− 0.33, p=0.02).Conclusion: Plasma concentration of dimethylarginines differs between patients with AMI and healthy volunteers. The study’s novel finding is that SDMA is an independent predictor of MACE during a 3.5 year follow-up period after AMI.Keywords: nitric oxide, L-arginine, acute myocardial infarction, major adverse cardiovascular events, prognosis

Keywords

• nitric oxide
• l-arginine
• acute myocardial infarction
• major adverse cardiovascular events
• prognosis