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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2536.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Asymmetric Dimethylarginine Predicts Major Adverse Cardiovascular Events in Patients With Advanced Peripheral Artery Disease

Friedrich Mittermayer; Katarzyna Krzyzanowska; Markus Exner; Wolfgang Mlekusch; Jasmin Amighi; Schila Sabeti; Erich Minar; Markus Müller; Michael Wolzt; Martin Schillinger

From the Department of Clinical Pharmacology (F.M., M.M., M.W.), Medical University Vienna; the Department of Internal Medicine I (K.K.), Rudolfstiftung Hospital, Vienna; the Clinical Institute for Medical and Chemical Laboratory Diagnostics (M.E.), Medical University Vienna; and the Department of Internal Medicine II (W.M., J.A., S.S., E.M., M.S.), Division of Angiology, Medical University Vienna, Austria.

Correspondence to Friedrich Mittermayer, Medical University Vienna, Department of Clinical Pharmacology, AKH-Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. E-mail friedrich.mittermayer{at}meduniwien.ac.at

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.

Concentrations of the nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated in states of increased cardiovascular risk. We prospectively examined the relationship between ADMA and major adverse cardiovascular events (MACE) in patients with peripheral artery disease. High ADMA independently predicted MACE supporting its role as new cardiovascular risk marker.

Key Words: asymmetric dimethylarginine • major adverse cardiovascular events • nitric oxide • peripheral artery disease

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