Dataset Information

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

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.

SUBMITTER: Gasecka A

PROVIDER: S-EPMC8364360 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients.Post hoc analysis of the Hemodialysis (HEMO) Study.1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization.ADMA and SDMA measured in stored specimens.Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function).Mean age of patients was 57±14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9±0.2?mol/L) and SDMA levels (4.3±1.4?mol/L) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 ?mol/L), the highest ADMA quintile (?1.07?mol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68).Single time-point measurement of ADMA and SDMA.ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.