Abstract 5844: Increased Asymmetric Dimethylarginine and Decreased C-Type Natriuretic Peptide Have an Additive Unfavourable Effect on Arterial Function and Structure
Objective: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, is a determinant of endothelial dysfunction and C-type natriuretic peptide (CNP) which is highly expressed in vascular endothelium is likely to exert a strong antiatherogenic activity that might be a key in compensating for deficiencies in NO. In this study, we investigated the combined effect of high ADMA and low CNP levels on arterial function and structure.
Methods: ADMA and N-terminal fragment CNP (NT-proCNP) levels were measured 116 consecutive men (mean age 57 years). Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV), endothelial function with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid IMT. The distributions of ADMA and NT-proCNP were split by the median (0.62 μmol/L and 0.23 pmol/L, respectively) and accordingly subjects were stratified into those with high and low values.
Results: Stepwise regression analysis revealed that ADMA, CNP and the interaction of ADMA with CNP were independent predictors of FMD, PWV and IMT. The significant interaction between high ADMA and low CNP on arterial structure and function. is additionally reflected by the finding that the subgroup of high ADMA/low CNP exhibited the lower FMD and the higher PWV and IMT values compared with the subgroups of high ADMA/high CNP, low ADMA/low CNP and low ADMA/high CNP after adjustment for age and blood pressure (figure⇓).
Conclusion: Increased ADMA in conjunction with low CNP levels exert an additive detrimental effect on arterial function and structure, accelerating the vascular ageing process and promoting atherosclerosis.