Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine predict adverse events in patients undergoing noncardiac surgery

Objective: In patients with cardiovascular disease or organ failure, elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are associated with an increased risk of future cardiovascular events. We aimed to investigate elevated plasma ADMA concentrations as a prospective risk marker for adverse events in patients undergoing noncardiac surgery. Design: Prospective observational study. Setting., Two tertiary care centers. Patients: Four hundred and two patients scheduled for elective noncardiac surgery. Interventions. None. Measurements and Main Results: Patients were followed for 30 days after surgery for a predefined composite end point (death, myocardial infarction/acute coronary syndrome, acute heart failure, severe arrhythmia, embolism, or thrombosis). Plasma ADMA concentrations at baseline were determined by high-performance liquid chromatography. ADMA was only weakly (-0.2 < tau < 0.2) correlated with other risk markers and risk scores. In univariate logistic regression, per 0.1-mu mol/L increment in plasma ADMA concentration, the odds ratio to experience the primary end point increased by 1.26 (95% confidence interval 1.10-1.45, p = .001). In a multivariate logistic regression model adjusting for age, gender, current smoking, plasma creatinine, hypertension, diabetes, ischemic heart disease, highly sensitive C-reactive protein, revised cardiac risk index, type of surgery, high-risk surgery, ASA class, and study center, ADMA was found to be an independent risk marker. The odds ratio to experience the primary end point was 1.33 (95% confidence interval 1.12-1.59, p = .001) per 0.1-mu mol/L increase in the plasma ADMA concentration. Conclusions: Elevated plasma ADMA concentrations are independently associated with a higher risk for adverse events in the peri- and postoperative periods.