Asymmetric dimethylarginine enhances cardiovascular risk prediction in patients with chronic heart failure

Objective - The purpose of this study was to investigate whether elevated asymmetrical dimethylorginine (ADMA) concentrations are associated with increased cardiovascular risk in chronic heart failure (HF) patients. Methods and Results - 253 patients with symptomatic chronic HF and impaired left ventricular function (median age 70 years, 202 males) were followed for a median of 14.2 months (interquartile range 6.8 to 21.2). ADMA and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assessed by high performance liquid chromatography and by an enzyme-linked immunosorbent assay, respectively. Subjects with ADMA concentrations in the highest tertile had a significantly higher adjusted hazard ratio (HR; 2.00; 95% confidence interval [CI] 1.01 to 3.97) for occurrence of an end point (cardiac decompensation, major adverse cardiovascular events or all-cause mortality) compared with patients in the lowest tertile (P = 0.046) during the first 6 months of follow-up. NT-proBNP also identified subjects at risk before adjustment for confounders at 6 and 12 months of follow-up. HR for patients with ADMA and NT-proBNP in the highest tertile was significantly increased (3.68, CI 1.67 to 8.14; at 6 months follow-up) compared with patients without ADMA and NT-proBNP in the highest tertile (P < 0.001). Conclusions - Elevated ADMA plasma concentrations are associated with adverse cardiovascular outcome in patients with chronic HF. Quantification of ADMA with NT-proBNP improves risk stratification in this cohort.