Asymmetrical dimethylarginine (ADMA) and risk of acute coronary events - Does statin treatment influence plasma ADMA levels?

The purpose of this study was to evaluate the hypothesis that high serum levels of ADMA, an indicator of endothelial dysfunction, are associated with an elevated risk of acute coronary events in middle-aged men. To test the hypothesis that lipid lowering medication with statins lowers circulating ADMA levels, we also investigated the effect of simvastatin and atorvastatin treatment on plasma ADMA concentration. In a prospective nested case-control study in 150 middle-aged non-smoking men from Eastern Finland, those who were in the highest quartile for serum ADMA (>0.62 mumol/l) had a 3.9-fold (95% Cl: 1.25-12.3, P = 0.02) increase in risk of acute coronary events compared with other quartiles. In an 8-week randomised double-blind placebo-controlled trial, plasma ADMA concentrations remained unchanged in simvastatin 80 mg/day (n = 16), atorvastatin 40 mg/day (n = 16) and placebo (n = 16) groups over the study period. Our findings indicate that high serum levels of ADMA, a potential marker for endothelial dysfunction, may increase the risk of acute coronary syndromes. However, aggressive treatment with either simvastatin or atorvastatin did not reduce plasma ADMA levels. (C) 2003 Elsevier Ireland Ltd. All rights reserved.