Arterial Wave Reflections and Determinants of Endothelial Function: A Hypothesis Based on Peripheral Mode of Action

Background Pulse waveform analysis (PWA) for determination of augmentation index (AIx), a measure of arterial wave reflections, has been used to assess endothelial function, but only in combination with provocative pharmacologic testing. We hypothesized that AIx under basal conditions would be related to endothelial function as well. Methods We quantified arterial wave reflections as aortic AIx, using applanation tonometry of the radial artery, and PWA in 424 patients (mean age 64.6 years) undergoing coronary angiography. Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase, were determined with a validated ELISA assay. In a group of the patients (n = 160), pulse wave velocity (PWV) was measured invasively during catheter pullback. Statistics were Spearman’s correlation coefficient and multiple linear regression models. Results We observed a positive, statistically significant correlation between AIx and ADMA (R = 0.11, P = .03), that was closer in 134 patients up to 60 years of age (R = 0.28, P = .001). In the latter group, the correlation was independant of age, gender, smoking, lipids, heart rate, diastolic blood pressure (BP), the presence of hypertension or diabetes, and the extent of coronary artery disease. In contrast, we observed a significant (R = 0.19, P = .02) correlation between PWV and ADMA that disappeared after correction for age and BP. Conclusions Our cross-sectional data indicate that ADMA levels are associated with increased arterial wave reflections, most likely due to decreased NO activity in small arteries and arterioles. This relationship is more pronounced in patients up to 60 years of age.