Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia.

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.