Reference Intervals for Brachial Artery Flow-Mediated Dilation and the Relation With Cardiovascular Risk Factors

Abstract

Endothelial function, assessed using brachial artery flow-mediated dilation (FMD), predicts future cardiovascular disease (CVD) risk. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. In a retrospective study design, we pooled brachial artery FMD (acquired according to expert-consensus guidelines for FMD protocol and analysis) and participant characteristics/medical history from 5362 individuals (4–84 years; 2076 females). Healthy individuals (n=1403 [582 females]) were used to generate age-/sex-specific percentile curves. Subsequently, we included individuals with CVD risk factors, without overt disease (unmedicated n=3167 [1247 females] and medicated n=792 [247 females]). Multiple linear regression tested the relation of CVD risk factors (body mass index, blood pressure, cholesterol, diabetes, dyslipidemia, and smoking) with FMD. Healthy males showed a negative, curvilinear relation between FMD and age, while females revealed a negative linear relation that started higher but declined at a faster rate than males. Age- and sex-specific differences in FMD relate, at least partly, to baseline artery diameter. FMD was related to CVD risk factors in unmedicated (eg, systolic/diastolic blood pressure) and medicated individuals (eg, diabetes/dyslipidemia). Sex mediated some of these effects ( P <0.05), with normalization of FMD in medicated men, but not women with dyslipidemia. In conclusion, sex alters the age-related decline in FMD, which may partly be explained through differences in baseline diameter. Sex also alters the influence of some CVD risk factors and medication on FMD. This work improves interpretation and future use of the FMD technique.

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

“…Despite the absence of a control group due to the challenges posed by the pandemic, it can be argued that the baseline FMD values documented in our study population were generally low [21] and directly correlated with FEV 1 %, FVC% and DLCO% values. This direct correlation between the severity of pulmonary and vascular diseases was also confirmed at the end of PR.…”

“…To date, several laboratory and clinical tests have been proposed to measure endothelial function in humans [18]. Among them, flow-mediated dilation (FMD) is recognized as a non-invasive and accurate clinical method [19] and as a surrogate marker of subclinical atherosclerosis [20], with a good responsiveness to interventions and correlation with coronary endothelial function [21]. Moreover, FMD is currently considered an independent predictor of CV events [22], thus providing important prognostic data over and above traditional CV risk factors.…”

Oral vitamin C restores endothelial function during acute inflammation in young and older adults

“…Data indicate acute administration of oral vitamin C improves endothelial function in populations with, or at risk for, disease (coronary artery disease (Levine, Frie, et al, 1996 ), young smokers (Raitakari et al, 2000 )). Oral vitamin C is less effective, however, in middle‐age or older adults who are healthy (Eskurza et al, 2004a ) or have large (>75 th percentile (Holder et al, 2021 )) baseline FMDs (Duffy et al, 2001 ). The null effect of vitamin C on FMD may therefore not be surprising considering the relatively good health of the individuals enrolled in the present study who are not at high risk for cardiovascular disease, despite their lower baseline FMDs compared to recently published reference ranges in a smaller number of older adults (Holder et al, 2021 ).…”

Endothelial Dysfunction and Cardiovascular Disease: History and Analysis of the Clinical Utility of the Relationship

“…To this end, an understanding of the natural variance of endothelial function is needed. Using standardized assessment methods, age- and sex-specific reference values for brachial artery FMD were recently published which provides a normative reference for future research, and potentially for clinical practice [ 79 ].…”