Association of Asymmetric Dimethylarginine and Nitric Oxide with Cardiovascular Risk in Patients with End-Stage Liver Disease

Abstract

Background and objectives: Endothelial dysfunction has been proposed to be an underlying mechanism of the pronounced cardiovascular morbidity in end-stage liver disease (ESLD), but clinical evidence is still limited. In this study, we investigated the association of circulating levels of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) with estimated cardiovascular risk in patients with ESLD awaiting liver transplantation. Materials and Methods: ADMA and NO levels were measured in the sera of 160 adult ESLD patients. The severity of hepatic dysfunction was assessed by the model for end-stage liver disease (MELD) score. The cardiovascular risk was estimated with the European Society of Cardiology Systematic Coronary Risk Estimation (SCORE) index, which was used to dichotomize patients in the subgroups depicting higher and lower cardiovascular risk. Results: Severe hepatic dysfunction (MELD ≥ 18) was present in 38% of the patients, and a higher cardiovascular risk was present in almost half of the patients (N = 74). ADMA and NO both significantly increased with the progression of liver disease and were independently associated with higher cardiovascular risk. Fasting glucose also independently predicted a higher cardiovascular risk, while HDL cholesterol and the absence of concomitant hepatocellular carcinoma were protective factors. Conclusions: These results suggest a remarkable contribution of the deranged arginine/NO pathway to cardiovascular risk in patients with end-stage liver disease.

Keywords

• end-stage liver disease
• transplantation
• endothelial dysfunction
• cardiovascular risk
• asymmetric dimethylarginine
• nitric oxide