Urinary asymmetric dimethylarginine (ADMA) is a predictor of mortality risk in patients with coronary artery disease

Abstract

Background: Asymmetric dimethylarginine (ADMA) causes endothelial dysfunction by inhibiting endothelial nitric oxide synthase. Elevated ADMA plasma levels comprise a major risk factor for coronary artery disease (CAD) and predict coronary events. ADMA is metabolised by dimethylarginine dimethylaminohydrolases (DDAHs) to citrulline and dimethylamine (DMA) and is partly excreted unchanged via the kidney. Unlike circulating ADMA, very little is known about urinary ADMA and DMA concentrations and a predictive value in CAD patients.

Methods and results: Seventy-seven consecutive patients admitted to hospital because of stable angina (mean age 65.9 ± 1.1 years) were enrolled and followed-up for 28 [1-28] months. All patients underwent cardiac catheterization and were divided into patients with no CAD or 1-3-vessel disease (CAD 1-3). Urinary ADMA levels (corrected for creatinine excretion) were lower in severely diseased patients (CAD 3, p<0.05) whereas the DMA/ADMA ratio was significantly increased (p<0.05 CAD 3 vs. CAD 0). In a stepwise multivariate regression analysis the ADMA/creatinine ratio correlated with cardiac function (r=0.5, p<0.0001) and LDL concentrations (r=0.27, p=0.01). A total of 12 patients died during follow-up, 9 due to cardiovascular causes. Importantly, low urinary ADMA concentrations predicted future cardiovascular death (p<0.01) and overall death (p<0.05).

Conclusion: In CAD patients low urinary ADMA concentrations are associated with impaired cardiac function and predict cardiovascular as well as all-cause mortality. The potential clinical value of urinary ADMA as a new biomarker for the diagnosis of CAD or cardiac dysfunction is intriguing, but warrants further studies.