Background: Arterial stiffness is an independent determinant of cardiovascular outcome. However, the factors regulating arterial stiffness remain unclear. Endothelial nitric oxide may partly regulate arterial stiffness. We hypothesized that asymmetric dimethylarginine (ADMA) an endogenous inhibitor of nitric oxide synthase would correlate with arterial stiffness.

Methods: The Caerphilly Prospective Study (CaPS) is a longitudinal cohort study of a representative sample of 2512 men aged 49 to 59 years in Wales. In a subset of 850 men (mean age 73 years) we assessed arterial stiffness (aortic pulse wave velocity, PWV) and wave reflections (augmentation index, AIx). ADMA measurements were made on a subsample of 250 men from the top and bottom of the age-adjusted PWV distribution by ELISA (DLD Diagnostika).

Results: The mean and median PWV was 11.8 and 11.6 m/s (SD 3.8 m/s), mean AIx 30.6% (SD 7.5%) and mean and median ADMA was 1.2 umol/l and 0.89 umol/l (IQR 0.69, 1.78 umol/l). There was a positive dose-response association between PWV and ADMA values after adjustment for GFR, heart rate, mean arterial pressure and age. The geometric mean PWV values were 10.9 m/s, 11.4 m/s and 11.8 m/s per tertile of ADMA (p-value for trend =0.04). There was no association between ADMA and AIx (p-value for trend=0.91).

Conclusion: This study shows that ADMA levels are greater amongst subjects with an elevated PWV. As this study is cross-sectional, we cannot be sure whether inhibition of nitric oxide synthase leads to arterial stiffening or vice versa. Future prospective studies are required.