Abstract 11624: The L-Arginine-Asymmetric Dimethylarginine Ratio Independently Predicts Five-Year Survival in Patients with Dilated Cardiomyopathy
Background: The competitive inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), is an independent predictor of cardiovascular events and all-cause mortality in patients both at high and low risk for cardiovascular events including patients with chronic heart failure. Furthermore, the L-arginine-ADMA ratio has been associated with the severity of chronic heart failure. Therefore, we aimed to measure these biomarkers in patients with chronic heart failure and determine their prognostic value with regard to the etiology of heart failure.
Methods and Results: We determined plasma levels of L-arginine and ADMA in 341 patients with chronic heart failure, (n=226 with dilated cardiomyopathy (DCMP) and n=115 with ischemic cardiomyopathy (ICMP)). Regardless of the etiology, median (IQR) ADMA plasma levels were elevated and L-arginine and the L-arginine-ADMA ratio were decreased in patients with severe forms of heart failure (NYHA III or IV) when compared to milder forms (NYHA I or II) (ADMA 0.57 (0.14) vs. 0.54 (0.12) µmol/l, p<0.001; L-arginine 81.8 (39.1) vs. 92.6 (39.3), p<0.001). Plasma levels of ADMA and L-arginine as well as the L-arginine-ADMA ratio were similar in patients with DCMP and ICMP; however, the prognostic value of these biomarkers differed depending on the etiology. DCMP patients within the highest quartile of L-arginine-ADMA ratio had a significantly lower risk of all-cause mortality during five years of follow-up (HR: 0.35; 95% CI: 0.12-0.98, p=0.046) compared to those in the lowest quartile after adjustment for other significant predictors from the univariate analysis. In patients with ICMP no association of outcome with the L-arginine-ADMA ratio was apparent.
Conclusion: Our findings suggest that patients with chronic heart failure due to DCMP with low L-arginine-asymmetric dimethylarginine ratios are at increased risk for death and may benefit from supplementation with L-arginine.
- © 2011 by American Heart Association, Inc.