Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality--an update on patient populations with a wide range of cardiovascular risk.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthases. By inhibiting NO formation, ADMA causes endothelial dysfunction, vasoconstriction, elevation of blood pressure, and aggravation of experimental atherosclerosis. Cross-sectional studies in humans have revealed that ADMA plasma concentration is elevated in numerous populations with vascular diseases or at high cardiovascular risk. However, the potential causal relationship between elevated ADMA and cardiovascular events and mortality in humans can only be revealed in prospective clinical studies. This review gives an overview of currently available data from prospective clinical studies in which ADMA has been measured in populations at high, intermediate, or low global vascular risk. Although the analytical methods used to quantify ADMA varied and statistical approaches to assess the association of ADMA with risk differed, these data reveal that ADMA is significantly associated with an increased risk of incident cardiovascular events and total mortality in subjects at a broad range of global risk. Hazard ratios were mostly in a range comparable to that of traditional cardiovascular risk markers even after multivariable adjustments, suggesting that ADMA may be suitable as a diagnostic marker for risk assessment, and that the biochemical pathways that regulate ADMA may be promising therapeutic approaches to treat cardiovascular disease in the future.