Elevated plasma levels of
asymmetric dimethylarginine (ADMA) have been associated with attenuated endothelium-dependent vasodilation in hypercholesterolemic patients. However, whether lowering of plasma
cholesterol concentration by hydroxymethylglutaryl
coenzyme A reductase inhibitors (
statins) can reduce plasma ADMA levels is still not clear. This study was a multicenter, randomized, double-blind, placebo-controlled design including 46 patients with elevated
low-density lipoprotein cholesterol levels. Patients were randomized into 2 groups:
rosuvastatin 10 mg/day and placebo for 6 weeks. Plasma levels of ADMA,
8-isoprostane (as a marker of oxidative stress),
homocysteine, and
high-sensitivity C-reactive protein were measured at baseline and 6 weeks later. Endothelial function assessed by flow-mediated vasodilation of the brachial artery was performed in 11 patients in the
rosuvastatin group and in 12 in the placebo group. Baseline characteristics of both groups were similar, and the plasma ADMA levels were significantly correlated with
8-isoprostane (r = 0.388, p = 0.008). After 6 weeks of treatment, plasma ADMA levels were significantly reduced in the
rosuvastatin group (from 0.60 +/- 0.19 to 0.49 +/- 0.10 micromol/L, p <0.001). Increases in flow-mediated vasodilation were positively correlated with reductions in plasma levels of ADMA (p = 0.017) and
low-density lipoprotein cholesterol (p <0.001). Thus, our findings suggest that treatment with
rosuvastatin in patients with
hypercholesterolemia may lead to a significant reduction in plasma ADMA levels, which appear to be related to the improvement in endothelial function by
rosuvastatin.