ADMA is independently related to flow-mediated vasodilation in subjects at low cardiovascular risk

Background: Increased plasma concentrations of asymmetric dimethylarginine (ADMA) contribute to impair endothelial function in patients with established cardiovascular disease (CVD) and/or individuals with clinical syndromes known to increase CVD. However, the impact of ADMA on endothelial function in apparently healthy individuals has not been determined. Materials and methods: To address this issue, we measured endothelial-dependent vasodilatation in response to forearm ischaemia (flow-mediated vasodilatation, FMD) in 111 non-smoking, healthy volunteers with low CVD risk by the Framingham risk equation. Measurements were also made of multiple anthropometric, metabolic, and dynamic variables related to FMD. L-arginine and its methylated derivates (ADMA and SDMA) were quantified by high-liquid pressure chromatography. Results: After adjustment by gender, lower values for FMD were significantly associated with increases in plasma ADMA concentrations (ANOVA linear trend by FMD tertiles, P < 0.05) as well as in brachial artery diameter (partial r = -0.352, P = 0.001), body mass index (-0.337, P = 0.001), fasting insulin (-0.368, P < 0.001) and high-sensitivity C-reactive protein (-0.283, P = 0.007) plasma concentrations, and with decreased HDL cholesterol (0.233, P = 0.026). Multiple linear regression analysis indicated that the only statistically significant predictors of FMD were brachial artery diameter (P < 0.001), ADMA (P < 0.05) and fasting plasma insulin (P < 0.001) concentrations. Conclusions: In conclusion, a significant relationship between increases in plasma ADMA concentration and lower values of FMD is not limited to patients with clinical syndromes related to CVD, but can also be seen in healthy subjects at low global CVD risk.