The impact of baseline diameter on flow-mediated dilation differs in young and older humans

Flow-mediated dilation (FMD) has become a commonly applied approach for the assessment of vascular function and health, but methods used to calculate FMD differ between studies. For example, the baseline diameter used as a benchmark is sometimes assessed before cuff inflation, whereas others use the diameter during cuff inflation. Therefore, we compared the brachial artery diameter before and during cuff inflation and calculated the resulting FMD in healthy children (n = 45; 10 ± 1 yr), adults (n = 31; 28 ± 6 yr), and older subjects (n = 22; 58 ± 5 yr). Brachial artery FMD was examined after 5 min of distal ischemia. Diameter was determined from either 30 s before cuff inflation or from the last 30 s during cuff inflation. Edge detection and wall tracking of high resolution B-mode arterial ultrasound images was used to calculate conduit artery diameter. Brachial artery diameter during cuff inflation was significantly larger than before inflation in children (P = 0.02) and adults (P < 0.001) but not in older subjects (P = 0.59). Accordingly, FMD values significantly differed in children (11.2 ± 5.1% vs. 9.4 ± 5.2%; P = 0.02) and adults (7.3 ± 3.2% vs. 4.6 ± 3.3%; P < 0.001) but not in older subjects (6.3 ± 3.4% vs. 6.0 ± 4.2%; P = 0.77). When the diameter before cuff inflation was used, an age-dependent decline was evident in FMD, whereas FMD calculated using the diameter during inflation was associated with higher FMD values in older than younger adults. In summary, the inflation of the cuff significantly increases brachial artery diameter, which results in a lower FMD response. This effect was found to be age dependent, which emphasizes the importance of using appropriate methodology to calculate the FMD

Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans

Flow-mediated dilatation (FMD) has become a commonly applied approach for the assessment of vascular function and health in humans. Recent studies emphasize the importance of normalizing the magnitude of FMD to its apparent eliciting stimulus, the postdeflation arterial shear. However, the relationship between shear stress and the magnitude of FMD may differ between groups. The aim of this study was to examine the relationship between the brachial FMD and four different indexes of postdeflation shear rate (SR) in healthy children (n = 51, 10 ± 1 yr) and young (n = 57, 27 ± 6 yr) and older (n = 27, 58 ± 4 yr) adults. SR was calculated from deflation (time 0) until 9 s (peak), 30 s (0–30), 60 s (0–60), or until the time-to-peak diameter in each individual (0-ttp). Edge detection and wall tracking of high resolution B-mode arterial ultrasound images were used to calculate the conduit artery diameter. In young adults, the brachial artery FMD demonstrated a significant correlation with the area under the SR curve (SRAUC) 0–30 s (r2 = 0.12, P = 0.009), 0–60 s (r2 = 0.14, P = 0.005), and 0-ttp (r2 = 0.14, P = 0.005) but not for the peak SRAUC 0–9 s (r2 = 0.04, P = 0.12). In children and older adults, the magnitude of the brachial artery FMD did not correlate with any of the four SRAUC stimuli. These findings suggest that in young subjects, postdeflation SRAUC correlates moderately with the magnitude of the FMD response. However, the relationship between FMD and postdeflation shear appears to be age dependent, with less evidence for an association in younger and older subjects. Therefore, we support presenting SRAUC stimuli but not normalizing FMD responses for the SRAUC when using this technique

Exercise-mediated changes in conduit artery wall thickness in humans: role of shear stress

Item does not contain fulltextEpisodic increases in shear stress have been proposed as a mechanism that induces training-induced adaptation in arterial wall remodeling in humans. To address this hypothesis in humans, we examined bilateral brachial artery wall thickness using high-resolution ultrasound in healthy men across an 8-wk period of bilateral handgrip training. Unilaterally, shear rate was attenuated by cuff inflation around the forearm to 60 mmHg. Grip strength, forearm volume, and girth improved similarly between the limbs. Acute bouts of handgrip exercise increased shear rate (P < 0.005) in the noncuffed limb, whereas cuff inflation successfully decreased exercise-induced increases in shear. Brachial blood pressure responses similarly increased during exercise in both the cuffed and noncuffed limbs. Handgrip training had no effect on baseline brachial artery diameter, blood flow, or shear rate but significantly decreased brachial artery wall thickness after 6 and 8 wk (ANOVA, P < 0.001) and wall-to-lumen ratio after week 8 (ANOVA, P = 0.005). The magnitude of decrease in brachial artery wall thickness and wall-to-lumen ratio after exercise training was similar in the noncuffed and cuffed arms. These results suggest that exercise-induced changes in shear rate are not obligatory for arterial wall remodeling during a period of 8 wk of exercise training in healthy humans

Is the ratio of flow-mediated dilation and shear rate a statistically sound approach to normalization in cross-sectional studies on endothelial function?

Contains fulltext : 80072thijssen.pdf (publisher's version ) (Closed access)It has been deemed important to normalize flow-mediated dilation (FMD), a marker of endothelial function, for between-subject differences in the eliciting shear rate (SR) stimulus. Conventionally, FMD is divided by the area under the curve of the SR stimulus. In the context of a cross-sectional comparison across different age cohorts, we examined whether this ratio approach adhered to established statistical assumptions necessary for reliable normalization. To quantify brachial artery FMD and area under the curve of SR, forearm cuff inflation to suprasystolic pressure was administered for 5 min to 16 boys aged 10.9 yr (SD 0.3), 48 young men aged 25.3 yr (SD 4.2), and 15 older men aged 57.5 yr (SD 4.3). Mean differences between age groups were statistically significant (P < 0.001) for nonnormalized FMD [children: 10.4% (SD 5.4), young adults: 7.5% (SD 2.9), older adults: 5.6% (SD 2.0)] but not for ratio-normalized FMD (P = 0.10). Moreover, all assumptions necessary for reliable use of ratio-normalization were violated, including regression slopes between SR and FMD that had y-intercepts greater than zero (P < 0.05), nonlinear and unstable relations between the normalized ratios and SR, skewed data distributions, and heteroscedastic variance. Logarithmic transformation of SR and FMD before ratio calculation improved adherence to these assumptions and resulted in age differences similar to the nonnormalized data (P = 0.03). In conclusion, although ratio normalization of FMD altered findings about age differences in endothelial function, this could be explained by violation of statistical assumptions. We recommend that exploration of these assumptions should be routine in future research. If the relationship between SR and FMD is generally found to be weak or nonlinear or variable between samples, then ratio normalization should not be applied

Seasonal reduction in physical activity and flow-mediated dilation in children

Purpose: Cardiovascular disease is a process that has its origins in childhood. Endothelial dysfunction is the earliest detectable manifestation of cardiovascular disease. This study aimed to assess the impact of seasonal changes in physical activity (PA) and body composition on conduit artery endothelial function in children. Method: We studied 116 children (70 girls aged 10.7 &plusmn; 0.3 yr and 46 boys aged 10.7 &plusmn; 0.3 yr) on two occasions; in the northern summer (June) and late autumn (November). We assessed flow-mediated dilation (FMD) using high-resolution Doppler ultrasound. Body composition was measured by dual-energy x-ray absorptiometry. PA was assessed using accelerometry. Results: FMD (10.0% &plusmn; 4.3% to 7.9% &plusmn; 3.9%, P &lt; 0.001) and PA (94.1 &plusmn; 34.8 to 77.8 &plusmn; 33.7 min&middot;d-1, P &lt; 0.01) decreased, while percentage body fat increased (27.6% &plusmn; 6.8% to 28.0% &plusmn; 6.6%, P &lt; 0.001) between summer and autumn. Decreases in FMD correlated with decreases in high-intensity PA (r = 0.23, P = 0.04), and change in high-intensity PA was the only predictor of change in FMD. No relationships were evident between changes in body composition and FMD. Conclusions: Vascular function decreased between summer and autumn in this cohort. There were no relationships between change in FMD and changes in body composition or low/moderate-intensity PA. The associations between FMD and high-intensity PA suggests that future interventions should encourage this form of behavior, particularly at the times of year associated with lower PA.<br /

Time course of change in vasodilator function and capacity in response to exercise training in humans

Studies of the impact of exercise training on arterial adaptation in healthy subjects have produced disparate results. It is possible that some studies failed to detect changes because functional and structural adaptations follow a different time course and may therefore not be detected at discrete time points. To gain insight into the time course of training-induced changes in artery function and structure, we examined conduit artery flow mediated dilatation (FMD), an index of nitric oxide (NO)-mediated artery function, and conduit dilator capacity (DC), a surrogate marker for arterial remodelling, in the brachial and popliteal arteries of 13 healthy male subjects (21.6 ± 0.6 years) and seven non-active controls (22.8 ± 0.2 years) studied at 2-week intervals across an 8-week cycle and treadmill exercise training programme. Brachial and popliteal artery FMD and DC did not change in control subjects at any time point. FMD increased from baseline (5.9 ± 0.5%) at weeks 2 and 4 (9.1 ± 0.6, 8.5 ± 0.6%, respectively, P < 0.01), but returned towards baseline levels again by week 8 (6.9 ± 0.7%). In contrast, brachial artery DC progressively increased from baseline (8.1 ± 0.4%) at weeks 2, 4, 6 and 8 (9.2 ± 0.6, 9.9 ± 0.6, 10.0 ± 0.5, 10.5 ± 0.8%, P < 0.05). Similarly, popliteal artery FMD increased from baseline (6.2 ± 0.7%) at weeks 2, 4 and 6 (9.1 ± 0.6, 9.5 ± 0.6, 7.8 ± 0.5%, respectively, P < 0.05), but decreased again by week 8 (6.5 ± 0.6%), whereas popliteal DC progressively increased from baseline (8.9 ± 0.4%) at week 4 and 8 (10.5 ± 0.7, 12.2 ± 0.6%, respectively, P < 0.05). These data suggest that functional changes in conduit arteries occur rapidly and precede arterial remodelling in vivo. These data suggest that complimentary adaptations occur in arterial function and structure and future studies should adopt multiple time point assessments to comprehensively assess arterial adaptations to interventions such as exercise training in humans