Plasma Concentration Of Asymmetric Dimethylarginine And Adverse Outcomes In Patients With Stroke: A Prospective Case-control Study

Background and Objective The plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), has been linked to endothelial dysfunction and pathogenesis of atherosclerosis. The present study was initiated to investigate the relationship between plasma ADMA level and stroke, and tested the predictive power of ADMA for adverse vascular events and overall mortality in patients with stroke.Methods We recruited 241 stroke patients (131 cerebral thrombosis, 35 lacunar infarction and 75 cerebral hemorrhage) and 234 controls. Plasma concentrations of ADMA were determined by high-performance liquid chromatography (HPLC). Fatal and non-fatal vascular diseases and all-cause deaths were accurately recorded over the follow-up period of 59.1±9.3 (mean±SD) months.Results Plasma ADMA level in controls was 0.55 (0.23-2.80) [median (range)]μmol/L. Compared with controls, plasma concentrations of ADMA were elevated in cerebral thrombosis [0.63(0.34-1.57)μmol/L, P<0.001], lacunar infarction [0.59(0.46-1.19)μmol/L, P<0.05], intracerebral hemorrhage [0.65(0.35-1.31)μmol/L, P<0.001] and stroke as a whole [0.63(0.34-1.57)μmol/L, P<0.001]. In a logistic regression model, elevated plasma ADMA was associated independently with an increased risk of 2.49-fold [95% confidence interval (95% CI), 1.58-3.93, P<0.001] for stroke. During a mean follow-up of 59.1 months, 21 cases and 16 controls dropped out. The analyses based on 220 cases and 218 controls showed that 59 (26.8%) vascular events (fatal and non-fatal) in cases and 10 (4.6%) in controls occurred during the follow-up period. Fifty-one (23.2%) cases and 19 (8.7%) controls died and 40 and 9 of them in cases and controls, respectively, were due to vascular causes. In a Cox regression model, high plasma level of ADMA increased risk of severe vascular events by 1.88 folds (1.27-4.06, P<0.05) and overall mortality by 2.60 folds (1.17-5.74, P<0.05) in patients with stroke independent of other risk factors.Conclusion Elevated plasma ADMA concentration is associated with increased risk of stroke independent of other variables and is a strong independent predictor of severe vascular events and all-cause mortality in patients with stroke.