Superficial Femoral Artery Flow-mediated Dilation Research Articles

Variability of flow-mediated dilation across lower and upper limb conduit arteries.

Endothelial dysfunction is an early predictor of atherosclerosis and cardiovascular disease. Flow-mediated dilation (FMD) is the goldstandard to assess endothelial function in humans. FMD reproducibility has been mainly assessed in the brachial artery (BA) with limited research in lower limb arteries. The purpose of this study was to compare FMD reproducibility in the upper limb BA and lower limb superficial femoral artery (SFA) in young healthy adults.Fifteen young healthy adults (nine males; six females) underwent FMD, resting diameter, velocity, and shear rate measurements on three occasions to determine intra-and inter-day reproducibility in both BA and SFA, assessed by coefficient of variation (CV), intraclass correlation coefficient (ICC), and Bland-Altman plots.BA FMD CVs (intra-day: 4.2%; inter-day: 8.7%) and ICCs (intra-day: 0.967; inter-day: 0.903) indicated excellent reproducibility and reliability, while for SFA FMD, both CVs (intra-day: 11.6%; inter-day: 26.7%) and ICCs (intra-day: 0.898; inter-day: 0.651) showed good/moderate reproducibility and reliability. BA FMD was significantly more reproducible than SFA FMD (p < 0.05). Diameter reproducibility was excellent and similar between arteries, while resting velocity and shear rate have lower reproducibility in the BA compared to SFA. Bland-Altman plots displayed no proportional and fixed bias between measurements.In summary, SFA FMD is less reproducible than BA FMD, with identical volume of ultrasound training. Given the increasing interest in using SFA FMD to test the efficacy of interventions targeting lower limb's vascular health and as a potential biomarker for peripheral arterial disease risk, future studies should ensure higher levels of training for adequate reproducibility.

Improvements in vascular function in response to acute lower limb heating in young healthy males and females.

Regular exposure to passive heat stress improves vascular function, but the optimal heating prescription remains undefined. Local limb heating is more feasible than whole body heating, but the evidence demonstrating its efficacy is lacking. The purpose of this study was to determine whether acute improvements in vascular function can be achieved with lower limb heating in 16 young healthy individuals (8 female, 8 male). In separate visits, participants underwent 45 min of ankle- and knee-level hot water immersion (45°C). A subset of seven participants also participated in a time-control visit. Endothelial function was assessed through simultaneous brachial and superficial femoral artery flow-mediated dilation (FMD) tests. Macrovascular function was quantified by %FMD, whereas microvascular function was quantified by vascular conductance during reactive hyperemia. Arterial stiffness was assessed through carotid-femoral and femoral-foot pulse wave velocity (PWV). Plasma concentrations of interleukin-6 and extracellular heat shock protein-72 (eHSP72) were used as indicators of inflammation. Our findings showed that 45 min of lower limb heating-regardless of condition-acutely improved upper limb macrovascular endothelial function (i.e., brachial %FMD; Pre: 4.6 ± 1.7 vs. Post: 5.4 ± 2.0%; P = 0.004) and lower limb arterial stiffness (i.e., femoral-foot PWV; Pre: 8.4 ± 1.2 vs. Post: 7.7 ± 1.1 m/s; P = 0.011). However, only knee-level heating increased upper limb microvascular function (i.e., brachial peak vascular conductance; Pre: 6.3 ± 2.7 vs. Post: 7.8 ± 3.5 mL/min⋅mmHg; P ≤ 0.050) and plasma eHSP72 concentration (Pre: 12.4 ± 9.4 vs. Post: 14.8 ± 9.8 ng/mL; P ≤ 0.050). These findings show that local lower limb heating acutely improves vascular function in younger individuals, with knee-level heating improving more outcome measures.NEW & NOTEWORTHY This study demonstrates that lower limb hot water immersion is an effective strategy for acutely improving vascular function in young, healthy males and females, thereby encouraging the development of accessible modes of heat therapy for vascular health.

Sitting cross-legged for 30 min alters lower limb shear stress pattern but not flow-mediated dilation or arterial stiffness.

Prolonged sitting decreases lower limb endothelial function via sustained reductions in mean shear rate. We tested whether 30 min of sitting cross-legged differentially impacts superficial femoral artery shear rate pattern, flow-mediated dilation (FMD), and leg pulse-wave velocity (PWV) compared with sitting flat-footed. Sitting cross-legged attenuated the reduction in mean and antegrade shear rate and increased arterial pressure compared with sitting flat-footed. Superficial femoral artery FMD and leg PWV were unaltered following either sitting position.

Effects of prior aerobic exercise on sitting-induced vascular dysfunction in healthy men.

Acute aerobic exercise prevents sitting-induced impairment of flow-mediated dilation (FMD). Further, evidence suggests that sitting-induced impairment of FMD occurs via an oxidative stress-dependent mechanism that disrupts endothelial function. We hypothesized that acute aerobic exercise would prevent impairment of femoral artery FMD by limiting oxidative stress responses that increase endothelin-1 (ET-1) levels and disrupt nitric oxide (NO) status. In a randomized, cross-over study, healthy men (n = 11; 21.2 ± 1.9years) completed two 3h sitting trials that were preceded by 45min of either quiet rest (REST) or a single bout of continuous treadmill exercise (65% maximal oxygen consumption) (EX). Superficial femoral artery FMD, plasma glucose, malondialdehyde (MDA), ET-1, arginine (ARG) and its related metabolites [homoarginine (HA), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)] were assessed at baseline, 1h following EX (or REST) (0h), and at 1h intervals during 3h of uninterrupted sitting. Data were analyzed using repeated measures ANOVA. During REST, femoral artery FMD declined from baseline (2.6 ± 1.8%) at 1, 2, and 3h of sitting and resting shear rate decreased at 3h. In contrast, when sitting was preceded by EX, femoral artery FMD (2.7 ± 2.0%) and resting shear rate responses were unaffected. No between trial differences were detected for plasma glucose, MDA, ET-1, ARG, HA, ADMA, or SDMA. Prior aerobic exercise prevented the decline in femoral artery FMD that is otherwise induced by prolonged sitting independent of changes in oxidative stress, ET-1, and NO status.

Effect of exercise-induced muscle damage on vascular function and skeletal muscle microvascular deoxygenation.

This paper investigated the effects of unaccustomed eccentric exercise‐induced muscle damage (EIMD) on macro‐ and microvascular function. We tested the hypotheses that resting local and systemic endothelial‐dependent flow‐mediated dilation (FMD) and microvascular reactivity would decrease, V˙O2max would be altered, and that during ramp exercise, peripheral O2 extraction, evaluated via near‐infrared‐derived spectroscopy (NIRS) derived deoxygenated hemoglobin + myoglobin ([HHb]), would be distorted following EIMD. In 13 participants, measurements were performed prior to (Pre) and 48 h after a bout of knee extensor eccentric exercise designed to elicit localized muscle damage (Post). Flow‐mediated dilation and postocclusive reactive hyperemic responses measured in the superficial femoral artery served as a measurement of local vascular function relative to the damaged tissue, while the brachial artery served as an index of nonlocal, systemic, vascular function. During ramp‐incremental exercise on a cycle ergometer, [HHb] and tissue saturation (TSI%) in the m. vastus lateralis were measured. Superficial femoral artery FMD significantly decreased following EIMD (pre 6.75 ± 3.89%; post 4.01 ± 2.90%; P < 0.05), while brachial artery FMD showed no change. The [HHb] and TSI% amplitudes were not different following EIMD ([HHb]: pre, 16.9 ± 4.7; post 17.7 ± 4.9; TSI%: pre, 71.0 ± 19.7; post 71.0 ± 19.7; all P > 0.05). At each progressive increase in workload (i.e., 0–100% peak), the [HHb] and TOI% responses were similar pre‐ and 48 h post‐EIMD (P > 0.05). Additionally, V˙O2max was similar at pre‐ (3.0 ± 0.67 L min−1) to 48 h post (2.96 ± 0.60 L min−1)‐EIMD (P > 0.05). Results suggest that moderate eccentric muscle damage leads to impaired local, but not systemic, macrovascular dysfunction.

Substantive hemodynamic and thermal strain upon completing lower-limb hot-water immersion; comparisons with treadmill running

ABSTRACTExercise induces arterial flow patterns that promote functional and structural adaptations, improving functional capacity and reducing cardiovascular risk. While heat is produced by exercise, local and whole-body passive heating have recently been shown to generate favorable flow profiles and associated vascular adaptations in the upper limb. Flow responses to acute heating in the lower limbs have not yet been assessed, or directly compared to exercise, and other cardiovascular effects of lower-limb heating have not been fully characterized. Lower-limb heating by hot-water immersion (30 min at 42°C, to the waist) was compared to matched-duration treadmill running (65-75% age-predicted heart rate maximum) in 10 healthy, young adult volunteers. Superficial femoral artery shear rate assessed immediately upon completion was increased to a greater extent following immersion (mean ± SD: immersion +252 ± 137% vs. exercise +155 ± 69%, interaction: p = 0.032), while superficial femoral artery flow-mediated dilation was unchanged in either intervention. Immersion increased heart rate to a lower peak than during exercise (immersion +38 ± 3 beats·min-1 vs. exercise +87 ± 3 beats·min-1, interaction: p < 0.001), whereas only immersion reduced mean arterial pressure after exposure (−8 ± 3 mmHg, p = 0.012). Core temperature increased twice as much during immersion as exercise (+1.3 ± 0.4°C vs. +0.6 ± 0.4°C, p < 0.001). These data indicate that acute lower-limb hot-water immersion has potential to induce favorable shear stress patterns and cardiovascular responses within vessels prone to atherosclerosis. Whether repetition of lower-limb heating has long-term beneficial effects in such vasculature remains unexplored.

Impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in older subjects

An inverse, dose-dependent relationship between retrograde shear rate and brachial artery endothelial function exists in young subjects. This relationship has not been investigated in older adults, who have been related to lower endothelial function, higher resting retrograde shear rate and higher risk of cardiovascular disease. AimTo investigate the impact of a step-wise increase in retrograde shear stress on flow-mediated dilation in older males in the upper and lower limbs. MethodsFifteen older (68 ± 9 years) men reported to the laboratory 3 times. We examined brachial artery flow-mediated dilation before and after 30-min exposure to cuff inflation around the forearm at 0, 30 and 60 mmHg, to manipulate retrograde shear rate. Subsequently, the 30-min intervention was repeated in the superficial femoral artery. Order of testing (vessel and intervention) was randomised. ResultsIncreases in cuff pressure resulted in dose-dependent increases in retrograde shear in both the brachial and superficial femoral artery in older subjects. In both the brachial and the superficial femoral artery, no change in endothelial function in response to increased retrograde shear was observed in older males (‘time’ P = 0.274, ‘cuff*time P = 0.791’, ‘cuff*artery*time P = 0.774’). ConclusionIn contrast with young subjects, we found that acute elevation in retrograde shear rate does not impair endothelial function in older humans. This may suggest that subjects with a priori endothelial dysfunction are less responsive or requires a larger shear rate stimulus to alter endothelial function.

Effect of prolonged sitting and breaks in sitting time on endothelial function.

Sitting time (ST) is associated with cardiovascular disease risk factors, whereas breaking ST has been reported to be beneficial for reducing cardiovascular risk. The objective of this study is to examine the effects of breaking ST on superficial femoral artery (SFA) endothelial function. 1) Prolonged sitting would induce endothelial dysfunction and changes in shear forces, and 2) breaking ST with brief periods of activity would prevent attenuation in endothelial function. Twelve nonobese men (24.2 ± 4.2 yr) participated in two randomized 3-h sitting trials. In the sitting (SIT) trial, subjects were seated on a firmly cushioned chair for 3 h without moving their lower extremities. In the breaking ST trial (ACT), subjects sat similar to the SIT trial but walked on a treadmill for 5 min at 2 mph at 30 min, 1 h 30 min, and 2 h 30 min during the sitting interval. SFA flow-mediated dilation (FMD) was assessed at baseline, 1 h, 2 h, and 3 h in each trial. Statistical analyses were performed using dependent variables SFA FMD and shear rates. Significance was set at P ≤ 0.05. In the SIT trial, there was a significant decline in SFA FMD from baseline to 3 h (baseline, 4.72% ± 3.78%; 1 h, 0.52% ± 0.85%; 2 h, 1.66% ± 1.11%; 3 h, 2.2% ± 2.15; P < 0.05 by ANOVA) accompanied by a decline in mean shear rate and antegrade shear rate but no difference in shear rate (area under the curve). By two-way repeated-measures ANOVA, ACT prevented the sitting-induced decline in FMD (baseline, 4.5% ± 2.3%; 1 h, 5.04% ± 2.85%; 2 h, 5.28% ± 5.05%; 3 h, 6.9% ± 4.5%) along with no decline in shear rates. Three hours of sitting resulted in a significant impairment in shear rate and SFA FMD. When light activity breaks were introduced hourly during sitting, the decline in FMD was prevented.

Antioxidant vitamin C prevents decline in endothelial function during sitting.

BackgroundThis study was designed to test the hypothesis that antioxidant Vitamin C prevents the impairment of endothelial function during prolonged sitting.Material/MethodsEleven men (24.2±4.4 yrs) participated in 2 randomized 3-h sitting trials. In the sitting without vitamin C (SIT) and the sitting with vitamin C (VIT) trial, participants were seated for 3 h without moving their legs. Additionally, in the VIT trial, participants ingested 2 vitamin C tablets (1 g and 500 mg) at 30 min and 1 h 30 min, respectively. Superficial femoral artery (SFA) flow-mediated dilation (FMD) was measured hourly for 3 h.ResultsBy a 1-way ANOVA, there was a significant decline in FMD during 3 h of SIT (p<0.001). Simultaneously, there was a significant decline in antegrade (p=0.04) and mean (0.037) shear rates. For the SIT and VIT trials by a 2-way (trial × time) repeated measures ANOVA, there was a significant interaction (p=0.001). Pairwise testing revealed significant between-SFA FMD in the SIT and VIT trial at each hour after baseline, showing that VIT prevented the decline in FMD 1 h (p=0.009), 2 h (p=0.016), and 3 h (p=0.004). There was no difference in the shear rates between SIT and VIT trials (p>0.05).ConclusionsThree hours of sitting resulted in impaired SFA FMD. Antioxidant Vitamin C prevented the decline in SFA FMD, suggesting that oxidative stress may contribute to the impairment in endothelial function during sitting.

B-26 Free Communication/Poster - Cardiorespiratory Fitness

Introduction: Sitting time is associated with multiple cardiovascular and metabolic disease risk factors. Breaking sitting time has been reported to have beneficial associations with cardiovascular and metabolic risk. The direct effects breaking sitting time on endothelial function, which is cross-sectionally and prospectively associated with risk of cardiovascular disease, are unknown. PURPOSE: The purpose of this study was to examine the direct effects of breaking sitting time on femoral artery endothelial function. We hypothesized that breaks in sitting time will prevent the attenuation in endothelial function associated with prolonged sitting. METHODS: Eleven non-obese, healthy men (23.36±3.23 yrs) participated in two randomized 3 hr sitting trials. Subjects reported to the lab in a 6 hr fasted state. Subjects sat on a cushioned Chair: with their legs perpendicular to the floor, with feet flat on the ground. In the prolonged sitting (SIT) trial, subjects were seated for 3 hrs without moving their lower extremities. In the breaking sitting time trial (ACT), subjects sat similar to the SIT trial, but walked on a treadmill for 5 min at 2 mph at 0:30 min, 1:30 hr and 2:30 hr. Superficial femoral artery (SFA) flow mediated dilation (FMD) was assessed as a measure of endothelial function at baseline, 1hr, 2hr and 3hr in each trial. Descriptive statistics were performed for subject characteristics and paired sample t-tests were performed to examine the differences at each time point between SIT and ACT trial. RESULTS: There was no significant difference between the SFA FMD% at baseline (SIT: 4.82±3.95; ACT: 4.49±2.29, P=.776). However there were significant differences at 1 hr (SIT 0.47±0.88; ACT 5.04±2.85, P=0.001), 2hr (SIT 1.64±1.16; ACT 5.28± 5.05, P=0.045) and 3hr (SIT2.26±2.25; ACT 6.91±4.5, P=0.004) with an effect of ACT to prevent the reduction in FMD associated with SIT. CONCLUSION: Three hours of continuous sitting resulted in a significant impairment in superficial femoral artery endothelial function. When breaks with brief modest activity were introduced during the sitting time, this reduction in endothelial function was prevented. Breaking sitting time may be a physiologically beneficial cost effective way of maintaining vascular health in the sedentary population.

Oral vitamin C prevents the attenuation in flow mediated dilation during prolonged sitting (546.3)

Prolonged sitting has been hypothesized to impair endothelial function via mechanisms involving oxidative stress. This study was designed to determine if Vitamin C prevents the decline in flow mediated dilation (FMD) during 3hr of sitting.Methods: Eleven inactive, non‐obese, healthy men (24.2±4.4 yrs) participated in two randomized 3 hr sitting trials, performed fasting in the morning on both occasions. In the prolonged sitting (SIT) trial, subjects were seated for 3 hours without moving their lower extremities. In the vitamin C trial (VIT) subjects sat similar to the SIT trial, but were asked to swallow two vitamin C tablets (1000 mg and 500 mg) at 0:30 and 1:30 hr respectively. Superficial femoral artery (SFA) FMD was measured every hour for 3 hrs. Paired sample t‐tests were performed to examine the differences at each time point between SIT and VIT trial. Significance was set at p蠄0.05.Results: Baseline SFA FMD% did not differ between the study conditions (SIT 5.05±3.77; VIT 2.74±2.32). However, FMD% was significantly different between conditions at 1hr (SIT 0.56±0.88; VIT 4.54±3.96) 2hr (SIT 1.76±1.10; VIT 5.28± 3.32) and 3hr (SIT 2.35±2.19; VIT 6.45±4.03).Conclusion: Our data demonstrate that acute oral vitamin C supplementation prevents the acute decline in SFA FMD with prolonged sitting, suggesting that oxidative stress may contribute to the associated impairment in endothelial function.Grant Funding Source: Supported by American College of Sports Medicine Foundation grant

Acute impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in humans.

Retrograde shear rate (SR) in the brachial artery (BA) is associated with endothelial dysfunction; a precursor to atherosclerosis. The BA does not typically manifest clinical atherosclerosis, whereas the superficial femoral artery (SFA) is more prone to developing plaque. Examine whether the impact of incremental levels of retrograde SR differs between atherosclerosis‐prone (i.e., SFA) and ‐resistant vessels (i.e., BA) in healthy men. Thirteen healthy young men reported three times to the laboratory. We examined BA flow‐mediated dilation (FMD) before and after 30‐min exposure to cuff inflation around the forearm at 0, 30, and 60 mmHg, to manipulate retrograde SR. Subsequently, the 30‐min intervention was repeated in the SFA, using the same cuff pressure as in the forearm. Order of testing (vessel and intervention) was randomized among subjects. We found a dose‐dependent increase in retrograde SR with 30 and 60 mmHg cuff inflation, which was present in both the BA and SFA (all P < 0.05). BA and SFA FMD decreased after the 30‐min intervention (“time”: P = 0.012), and this was dependent on cuff pressure (“cuff × time”: P = 0.024). A significant decrease in FMD was observed after 60 mmHg only and this change was similarly present in both arteries (“time × artery”: P = 0.227). Moreover, the BA and SFA demonstrate a similar relationship between changes in retrograde SR and FMD (r = 0.498 and 0.475, respectively). Our study demonstrates that acute exposure to an increase in retrograde shear leads to comparable decreases in FMD in atherosclerotic‐prone and ‐resistant conduit arteries in humans.

The specific role of gravitational accelerations for arterial adaptations

It is mostly agreed that arterial adaptations occur, among others, in response to changes in mechanical stimuli. Models like bed rest, spinal cord injury, or limb suspension have been applied to study vascular adaptations to unloading in humans. However, these models cannot distinguish the role of muscle contractions and the role of gravitational accelerations for arterial adaptation. The HEPHAISTOS orthosis allows normal ambulation, while it significantly reduces force generation in the lower leg muscles. Eleven subjects wore HEPHAISTOS unilaterally for 56 days and were followed up for another 4 wk. Arterial diameters, intima media thickness (IMT), flow-mediated dilation (FMD), and resting blood flow (BF(rest)) were measured using high-frequency ultrasonography. Arterial adaptations were investigated in the superficial femoral artery (SFA), the brachial artery (BA), and the carotid artery (CA). Mean SFA resting diameter was decreased from 6.57 mm (SD = 0.74 mm) at baseline to 5.77 mm (SD = 0.87 mm) at the end of the intervention (P < 0.001), whereas SFA wall-to-lumen ratio, SFA BF(rest), and SFA FMD remained unaffected throughout the study. The application of HEPHAISTOS had no effect on structure and function of the systemic control sites, the BA, and the CA. Our findings highlight the importance of muscular contractions for arterial diameter adaptations. Moreover, we propose that FMD and wall-to-lumen ratio are unaffected by ambulating with the HEPHAISTOS orthosis, which is suggestive of habitual acceleration profiles in the lower leg constituting an important stimulus for the maintenance of FMD and wall-to-lumen ratio.

Relationship between upper and lower limb conduit artery vasodilator function in humans

Brachial artery flow-mediated dilation (FMD) is a strong predictor of future cardiovascular disease and is believed to represent a "barometer" of systemic endothelial health. Although a recent study [Padilla et al. Exp Biol Med (Maywood) 235: 1287-1291, 2010] in pigs confirmed a strong correlation between brachial and femoral artery endothelial function, it is unclear to what extent brachial artery FMD represents a systemic index of endothelial function in humans. We conducted a retrospective analysis of data from our laboratory to evaluate relationships between the upper (i.e., brachial artery) vs. lower limb (superficial femoral n = 75; popliteal artery n = 32) endothelium-dependent FMD and endothelium-independent glyceryl trinitrate (GTN)-mediated dilation in young, healthy individuals. We also examined the relationship between FMD assessed in both brachial arteries (n = 42). There was no correlation between brachial and superficial femoral artery FMD (r(2) = 0.008; P = 0.46) or between brachial and popliteal artery FMD (r(2) = 0.003; P = 0.78). However, a correlation was observed in FMD between both brachial arteries (r(2) = 0.34; P < 0.001). Brachial and superficial femoral artery GTN were modestly correlated (r(2) = 0.13; P = 0.007), but brachial and popliteal artery GTN responses were not (r(2) = 0.08; P = 0.11). Collectively, these data indicate that conduit artery vasodilator function in the upper limbs (of healthy humans) is not predictive of that in the lower limbs, whereas measurement of FMD in one arm appears to be predictive of FMD in the other. These data do not support the hypothesis that brachial artery FMD in healthy humans represents a systemic index of endothelial function.

Endothelium-dependent and -independent vasodilation of the superficial femoral artery in spinal cord-injured subjects

Extreme inactivity of the legs in spinal cord-injured (SCI) individuals does not result in an impairment of the superficial femoral artery flow-mediated dilation (FMD). To gain insight into the underlying mechanism, the present study examined nitric oxide (NO) responsiveness of vascular smooth muscles in controls and SCI subjects. In eight healthy men (34 +/- 13 yr) and six SCI subjects (37 +/- 10 yr), superficial femoral artery FMD response was assessed by echo Doppler. Subsequently, infusion of incremental dosages of sodium nitroprusside (SNP) was used to assess NO responsiveness. Peak diameter was examined on a second day after 13 min of arterial occlusion in combination with sublingual administration of nitroglycerine. Resting and peak superficial femoral artery diameter in SCI subjects were smaller than in controls (P < 0.001). The FMD response in controls (4.2 +/- 0.9%) was lower than in SCI subjects (8.2 +/- 0.9%, P < 0.001), but not after correcting for area under the curve for shear rate (P = 0.35). When expressed as relative change from baseline, SCI subjects demonstrate a significantly larger diameter increase compared with controls at each dose of SNP. However, when expressed as a relative increase within the range of diameter changes [baseline (0%) - peak diameter (100%)], both groups demonstrate similar changes in response to SNP. Changes in diameter during SNP infusion and FMD response are larger in SCI subjects compared with controls. When these results are corrected, superficial femoral artery FMD and NO sensitivity in SCI subjects are not different from those in controls. This illustrates the importance of appropriate data presentation and suggests that, subsequent to structural inward remodeling of conduit arteries as a consequence of extreme physical inactivity, arterial function is normalized.