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

Aleksandra Gąsecka; Piotr Szwed; Karolina Jasińska; Oliwia Fidali; Aleksandra Kłębukowska; Ceren Eyileten; Marek Postula; Łukasz Szarpak; Tomasz Mazurek; Grzegorz Opolski; Krzysztof J Filipiak; Marcin Ufnal

doi:10.2147/JIR.S316078

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

J Inflamm Res. 2021 Aug 10:14:3797-3808. doi: 10.2147/JIR.S316078. eCollection 2021.

Affiliations

¹ 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, 02-097, Poland.
² Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, 02-097, Poland.
³ Bialystok Oncology Center, Bialystok, 15-027, Poland.
⁴ Maria Sklodowska-Curie Medical Academy in Warsaw, Warsaw, 03-411, Poland.
⁵ Department of Experimental Physiology and Pathophysiology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, 02-106, Poland.

Abstract

Purpose: 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: L-arginine; acute myocardial infarction; major adverse cardiovascular events; nitric oxide; prognosis.

Grants and funding

National Science Centre, Poland, grant no: 2020/37/B/NZ5/00366. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.