From short-term blood pressure variability to atherosclerosis: Relative roles of vascular stiffness and endothelial dysfunction

Abstract

Both arterial blood pressure (BP) average levels and short-term BP variability (BPV) relate to hypertension-mediated organ damage, in particular increased carotid artery intima-media thickness (IMT) and carotid-femoral pulse wave velocity (PWV). Endothelial dysfunction possibly mediates such damage. The authors aimed at further investigating such role in hypertensive patients. In 189 recently diagnosed, untreated hypertensive patients the authors evaluated, in a cross-sectional design, the relationships of BP average levels and short-term systolic (S) BPV (standard deviation of awake SBP or of 24-hour-weighted SBP) with IMT and PWV, and how much these relationships are explained by endothelial function parameters-brachial artery flow-mediated dilation (FMD) and digital reactive hyperemia index (RHI). Multivariable models assessed the strength of these relationships to derive a plausible pathogenetic sequence. Both average SBP values and our measures of SBPV were significantly related to IMT (24-hour mean SBP: r = .156, P = .034; 24-hour-weighted SBPV: r = .157, P = .033) and to PWV (24-hour mean SBP: r = .179, P = .015; 24-hour-weighted SBPV: r = .175; P = .018), but only poorly related to FMD or RHI (P > .05 for all). At univariable regression analysis, FMD and RHI were both related to IMT, (P < .001), but not to PWV. When FMD and RHI were added to average SBP and SBPV parameters in a multivariable model, both significantly (P < .005) contributed to predict IMT, but not PWV. Thus, endothelial dysfunction relates to IMT independently of BP parameters, but appears to play a minor role in the association between BP variability-related variables and arterial stiffening.

Keywords: arterial stiffness; blood pressure; blood pressure variability; flow-mediated dilation; hypertension; intima-media thickness; pulse wave velocity; reactive hyperemia index.

Conflict of interest statement

None by any of the authors.

© 2020 Wiley Periodicals LLC.

Figures

FIGURE 1

Mediation analysis to determine the relationship between parameters of 24‐h‐weighted systolic blood pressure variability (SBPV) and atherosclerotic target‐organ damage, as marked by the carotid artery intima‐media thickness (IMT) (Panel A) and the pulse wave velocity (PWV) (Panel B). SBPV appears to directly affect arterial stiffness (as indicated by PWV). SBPV does not appear, however, to affect parameters of endothelial function (as measured by the brachial artery flow‐mediated dilation (FMD) or the reactive hyperemia index (RHI)), which are, however, strongly related to IMT. SBPV might also affect carotid atherosclerosis (IMT) by other, still unexplored mechanisms. Data are reported as unstandardized regression coefficients (b) (in general, the higher this coefficient, the stronger the relationship) and relative 95% confidence interval (CI) in parentheses