Asymmetric dimethylarginine (ADMA) and the risk for coronary heart disease:: the multicenter CARDIAC study

The pathophysiological importance of asymmetric dimethylarginine (ADMA) for the development of endothelial dysfunction mediated through inhibition of the nitric oxide synthase is well documented. The aim of the multicenter CARDIAC study (Coronary Artery Risk Determination investigating the Influence of ADMA Concentration) was to assess the potential relationship between ADMA plasma concentration and the risk for coronary heart disease. This study involved a large sample of subjects from an unselected population of both sexes and with a broad range of established cardiovascular risk factors. Manifestation of cardiovascular disease, in particular when associated with other risk factors such as hypertension, hypercholesterolemia, diabetes mellitus, and smoking, was accompanied by elevated ADMA plasma concentrations. The ADMA plasma concentration increased significantly as the number of traditional risk factors present increased. A threshold ADMA plasma concentration of 1.75 mu mol/l was identified, above which the risk for coronary heart disease increased significantly. For patients below this threshold concentration, symmetric dimethylarginine (SDMA) levels above 1.45 mu mol/l helped to further identify subjects at risk. An increase in the ADMA plasma concentration by 1 mu mol/l resulted in a 2.35-times higher risk of coronary heart disease. The multicenter CARDIAC case control study supports the contention that ADMA can be regarded as a new marker for cardiovascular disease. The plasma concentration of ADMA may represent an additional parameter that, in conjunction with other established cardiovascular risk factors, may help identify patients with an increased risk of cardiovascular disease.