Asymmetric dimethylarginine predicts perioperative cardiovascular complications in patients undergoing medium-to-high risk non-cardiac surgery

OBJECTIVES: Perioperative cardiovascular events remain an important factor that affects surgery outcome. We assessed if asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, predicts perioperative risk, and if pre-operative supplementation with L-arginine/L-citrulline improves the plasma L-arginine/ADMA ratio. METHODS: In this prospective study, planned thoracic and/or abdominal surgery patients were randomized to receive L-arginine/L-citrulline (5 g/day) or placebo 1 to 5 days before surgery. We measured perioperative plasma ADMA and L-arginine levels. The primary outcome was a 30-day combined cardiovascular endpoint. RESULTS: Among 269 patients, 23 (8.6%) experienced a major adverse cardiovascular event. ADMA and C-reactive protein were significantly associated with the incidence of cardiovascular complications in the multivariable-adjusted analysis. The L-arginine plasma concentration was significantly higher on the day of surgery with L-arginine/L-citrulline supplementation compared with placebo. In patients with high pre-operative ADMA, there was a non-significant trend towards reduced incidence of the primary endpoint with L-arginine/L-citrulline supplementation (six vs. nine events). CONCLUSIONS: ADMA is a predictor of major adverse cardiovascular complications in the perioperative period for patients who are undergoing major abdominal and/or thoracic surgery. Supplementation with L-arginine/L-citrulline increased the L-arginine plasma concentration, enhanced the L-arginine/ADMA ratio, and induced a trend towards fewer perioperative events.