Hyperhomocysteinaemia is not associated with increased levels of asymmetric dimethylarginine in patients with ischaemic heart disease

BACKGROUND: Elevated plasma total homocysteine appears to be related to endothelial dysfunction and impaired nitric oxide production. We aimed to investigate [1] whether elevated levels of plasma total homocysteine are associated with high plasma levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, and [2] whether reduction of plasma total homocysteine levels by folate and vitamin B supplementation lowers plasma concentration of asymmetric dimethylarginine. MATERIALS AND METHODS: Sixty patients with ischaemic heart disease and with plasma total homocysteine levels of 15.0 micromol L-1 were randomized to open therapy with folic acid, pyridoxine and cyancobalamin for 3 months (n = 30) or to no treatment (n = 30). Samples were also obtained from 34 patients with plasma total homocysteine levels of 8.0 micromol L-1 on admission. RESULTS: Plasma asymmetric dimethylarginine concentrations in patients with elevated total homocysteine levels were not significantly higher (0.68 +/- 0.19 micromol L-1) than in patients with low total homocysteine levels (0.61 +/- 0.10 micromol L-1; P = 0.08). Plasma asymmetric dimethylarginine level in the vitamin supplemented group was 0.65 +/- 0.12 micromol L-1 before, and 0.64 +/- 0.12 micromol L-1 after 3 months of vitamin supplementation (NS). Plasma asymmetric dimethylarginine levels were correlated with serum cystatin C levels (P < 0.001). CONCLUSION: A nonsignificant trend to increased plasma levels of asymmetric dimethylarginine in patients with high plasma total homocysteine levels may be explained by concomitant subtle renal dysfunction. Substantial reduction of plasma total homocysteine did not affect the level of plasma asymmetric dimethylarginine.