L-Arginine Pathway Metabolites Predict 6 Months Outcome after Acute Ischemic Stroke

Background: Increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are associated with endothelial dysfunction. Here, we analyzed the relationship between L-arginine pathway metabolites and functional outcome of ischemic stroke at discharge and 6 months follow-up. Methods: Plasma concentration of L-arginine, ADMA, SDMA were investigated in 46 patients at post-stroke 24 h. Outcome measures were assessed by modified Rankin scale (mRS) at hospital discharge and 6 months follow-up. According to change in mRS score during the 6 months period, patients were divided into subgroups of improved, unchanged and worsened function. Predictive role of L-arginine pathway metabolites were explored in these outcome groups. Results: Significant inverse correlations were found between initial NIHSS and the L-arginine/ADMA, the L-arginine/SDMA ratios and L-arginine plasma concentration (all p<0.05, respectively). Patients with worsened mRS by 6 months had significantly higher L-arginine plasma concentrations at 24 post-stroke hours compared to patients with improved mRS (p<0.001) and unchanged mRS (p<0.005). The L-arginine/ADMA (p<0.004) and the L-arginin/ SDMA (p<0.002) ratios at 24 h were significantly higher among patients with worsened compared to improved mRS. Besides, clinical factors, such as BMI showed negative correlation with L-arginine/ADMA; creatinine showed positive correlation with L-arginine and L-arginine/ADMA; LDL showed positive correlation with L-arginine/SDMA ratio. Plasma concentration of ADMA was significantly higher among smokers compared to non-smokers. The L-arginine/ADMA, the L-arginine/SDMA ratios and L-arginine plasma concentration negatively correlated with change of mRS between hospital discharge and at 6 months. Conclusion: Our data indicate that lower L-arginine/SDMA ratio is associated with worse outcome on the shortterm, but these patients improve on the long-term resulting in association of lower ratios with improving mRS. In contrast, patients with high L-arginine and low mRS improve fast, but will not improve or may even worsen by 6 months indicating a time-dependent biological effect.