Abstract Body (Do not enter title and authors here): Background: Endothelial dysfunction affects arterial stiffness. While age and blood pressure are major determinants for the progression of arterial stiffness and both also affect endothelial dysfunction, it has not been clarified whether these factors affect arterial stiffness directly or mediated by endothelial dysfunction.
Methods: Flow-mediated vasodilatation in Japan (FMD-J) study was a multicenter prospective observational study to examine the clinical significance of FMD in the management of cardiovascular diseases and their risk factors. In this study, FMD and brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, were repeatedly measured three times {i.e., baseline, 1.5 year’s and 3 years’ follow-up (1.5fol and 3fol)} in 617 subjects under anti-hypertensive medication.
Results: In cross-sectional assessment at baseline, at 1.5fol and at 3fol, multiple linear regression analyses adjusted with covariates demonstrated that age and systolic blood pressure (SBP) were independently associated with baPWV. During the study period, baPWV was increased significantly (from 1621 ± 295 to 1626 ± 294 cm/s, P<0.001). The study participants were divided into two groups by the median of age or by that of SBP at baseline. The baPWV at 3fol was higher in age over median and in SBP over median as compared to the group of those under median (1537 ± 278 vs. 1714 ± 282, P<0.001, 1593 ± 297 vs. 1656 ± 288, P<0.001). In multivariate longitudinal assessments, age and SBP at baseline were significantly associated with baPWV at 1.5fol (beta 0.412, P<0.001 and beta 0.216, P<0.001) and that at 3fol (beta 0.424, P<0.001 and beta 0.115, P= 0.002), but not with FMD. Multivariate mediation analyses demonstrated that age and SBP at baseline were directly associated with baPWV at baseline, at 1.5fol and at 3fol, but no significate mediated effect of FMD was conformed at each study period.
Conclusion: In subjects under anti-hypertensive medication, the progression of arterial stiffness may be accelerated along with age and also along with the elevation of SBP. In there, age and blood pressure may directly affect the progression of arterial stiffness without mediating endothelial dysfunction.