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).


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.
Mittermayer
Friedrich
F
Medical University Vienna, Department of Clinical Pharmacology, AKH-Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. friedrich.mittermayer@meduniwien.ac.at
Krzyzanowska
Katarzyna
K
Exner
Markus
M
Mlekusch
Wolfgang
W
Amighi
Jasmin
J
Sabeti
Schila
S
Minar
Erich
E
Müller
Markus
M
Wolzt
Michael
M
Schillinger
Martin
M
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001158:Arteries; D002318:Cardiovascular Diseases / Q000209:etiology*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000150:complications*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012720:Severity of Illness Index
C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase