Abstract 5510: Arginine Methylation Index as Integrated Quantification of Arginine Methylation Provides Stronger Independent Risk Prediction of Long-term Cardiovascular Events than Individual Methylated Arginine Metabolites
Background: The prognostic value of asymmetric dimethylarginine (ADMA) is attributed to its role as an endogenous inhibitor of nitric oxide synthases (NOS). The relationship of related post-translational modification products of arginine methylation and cardiovascular disease (CVD) risks is uncertain.
Methods: Plasma was isolated from 1,011 subjects undergoing diagnostic cardiac catheterization, and future major adverse cardiac events (MACE, including myocardial infarction, stroke, and death) were investigated. Levels of ADMA, symmetric dimethylarginine (SDMA), and N-mono-methylarginine (MMA) were quantified by mass spectrometry, and their ratios [(ADMA+SDMA)/MMA], the arginine methylation index (Methy-IArg), were determined.
Results: After adjusting for Framingham risk factors, CRP, and creatinine clearance, elevated (4th vs. 1st quartile) plasma levels of both SDMA [2.0-fold (95%CI, 1.3–3.1)] and ADMA [1.5-fold (95%CI, 1.00–2.4)] remained associated with higher prevalence of CVD, whereas elevated levels of MMA [0.56-fold (95%CI, 0.36–0.87)] were paradoxically associated with lower CVD. While elevated ADMA and SDMA levels remained significant predictors, MethyIArg was the strongest independent predictor of incident MACE[2.4-fold (95%CI, 1.3 to 4.5)].
Conclusions: An integrated quantification of arginine methylation in the form of an “Arginine Methylation Index” provided the strongest independent risk prediction for incident major adverse cardiac events in stable patients undergoing elective cardiac evaluation, and significantly added to the prognostic utility of traditional risk factors.