Asymmetric dimethylarginine predicts major adverse cardiovascular events in patients with advanced peripheral artery disease

Objective - Circulating concentrations of asymmetric dimethylarginine ( ADMA), an endogenous inhibitor of nitric oxide synthesis, are elevated in conditions associated with increased cardiovascular risk. We investigated whether elevated ADMA concentrations predict major adverse cardiovascular events ( MACE) in patients with advanced peripheral artery disease ( PAD). Methods and Results - We prospectively enrolled 496 of 533 consecutive patients with PAD ( median age 70 years, 279 males). ADMA and L-arginine were assessed at baseline by high performance liquid chromatography. The occurrence of MACE ( myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, carotid revascularization, death) was evaluated during a follow-up of median 19 months ( interquartile range 11 to 25). One hundred eighty- two MACE were observed in 141 patients ( 28%). MACE occurred in 39% of the patients in the highest quartile and 26% of those in the lowest quartile of ADMA ( P = 0.016, log- rank test for all quartiles). Adjusted hazard ratios for occurrence of MACE for increasing quartiles of ADMA compared with the lowest quartile were 0.87 ( 95% confidence interval [ CI], 0.51 to 1.48), 1.12 ( 95% CI, 0.62 to 1.90), and 1.70 ( 95% CI, 1.02 to 2.88), respectively. We observed no association between cardiovascular outcome and L-arginine. Conclusions - High ADMA plasma concentrations independently predict MACE in patients with advanced PAD. This indicates that ADMA may be a new cardiovascular risk marker in these patients.