Variation In Flow-mediated Dilation Research Articles

Brachial flow-mediated dilation by continuous monitoring of arterial cross-section with ultrasound imaging.

Impairment of flow-mediated dilation of the brachial artery is a marker of endothelial dysfunction and often predisposes atherosclerosis and cardiovascular events. In this study, we propose a user-guided automated approach for monitoring arterial cross-section during hyperemic response to improve reproducibility and sensitivity of flow-mediated dilation. Ultrasound imaging of the brachial artery was performed in 11 volunteers in cross-sectional and in 5 volunteers in longitudinal view. During each examination, images were recorded continuously before and after inducing ischemia. Time-dilation curves of the brachial lumen cross-section were measured by user-guided automated segmentation of brachial images with the feed-forward active contour (FFAC) algorithm. %FMD was determined by the ratio of peak dilation to the baseline value. Each measurement was repeated twice in two sessions 1 h apart on the same arm to evaluate the reproducibility of the measurements. The intra-subject variation in flow-mediated dilation between two sessions (subject-specific) and inter-group variation in flow-mediated dilation with all the subjects within a session grouped together (group-specific) were measured for FFAC. The FFAC measurements were compared with the conventional diameter measurements made using echo tracking in longitudinal views. Flow-mediated dilation values for cross-sectional area were greater than those measured by diameter dilation: 33.1% for cross-sectional area compared to 22.5% for diameter. Group-specific flow-mediated dilation measurements for cross-sectional area were highly reproducible: 33.2% vs. 33.0% (p > 0.05) with coefficient of variation CV of 0.4%. The group-specific flow-mediated dilations measured by echo tracking for the two sessions were 21.1 vs. 23.9% with CV of 9%. Subject-specific CV for cross-sectional area by FFAC was 10% ± 2% versus 24% ± 10% for the conventional approach. Using correlation as a metric of evaluation also showed better performance for cross-sectional imaging: correlation coefficient, R, between two sessions for cross-sectional area was 0.92 versus 0.72 for the conventional approach based on diameter measurements. Peak dilation area measured by continuous automated monitoring of cross-sectional area of the brachial artery provides more reproducible and higher-sensitivity measurement of flow-mediated dilation compared to the conventional approach of using vascular diameter measured using longitudinal imaging.

735-P: Seasonal Variation in Vascular Function in People with Type 2 Diabetes Who Exercise Regularly

The purpose of this study was to investigate seasonal variation in vascular function in people with type 2 diabetes (T2D) who exercise regularly. Fourteen Japanese adults with uncomplicated T2D (5 men and 9 women, age: 65.9 ± 0.9 years, HbA1c: 7.1 ± 0.1%, mean ± SE). All patients exercised at our hospital for 5 years (January 2010-December 2014). Moderate intensity aerobic exercise using a treadmill or bicycle ergometer was performed for 40 min/day (frequency: ≥ 2 days/week). Vascular function, including flow-mediated dilation (FMD), cardio-ankle vascular index (CAVI), and ankle-brachial pressure index (ABI) in each season (spring: March-May, summer: June-August, fall: September-November, winter: December-February) were compared. Variation in FMD throughout the year was 1.0%, and the level in winter was significantly worse than in spring and summer (winter vs. spring and summer: 3.5 ± 0.1% vs. 4.4 ± 0.1% and 4.6 ± 0.1%; p < 0.01 and p < 0.01, respectively) (Figure). However, CAVI and ABI showed no significant change throughout the year. These results suggested that FMD rather than CAVI and ABI might show seasonal variation, even in people with T2D who exercise regularly. It is important to consider these characteristics when managing T2D. Disclosure H. Honda: None. M. Igaki: None.

Lysosomal Acid Lipase as a Molecular Target of the Very Low Carbohydrate Ketogenic Diet in Morbidly Obese Patients: The Potential Effects on Liver Steatosis and Cardiovascular Risk Factors.

A very low carbohydrate ketogenic diet (VLCKD) is an emerging technique to induce a significant, well-tolerated, and rapid loss of body weight in morbidly obese patients. The low activity of lysosomal acid lipase (LAL) could be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is a common feature in morbidly obese patients. Fifty-two obese patients suitable for a bariatric surgery intervention underwent a 25-day-long VLCKD. The biochemical markers of glucose and lipid metabolism, and flow-mediated dilation (FMD) of the brachial artery were measured before and after VLCKD. LAL activity was measured using the dried blood spot technique in 20 obese patients and in a control group of 20 healthy, normal-weight subjects. After VLCKD, we observed a significant reduction in body mass index, fasting glucose, insulinemia, and lipid profile parameters. No significant variation in FMD was observed. The number of patients with severe liver steatosis significantly decreased. LAL activity significantly increased, although the levels were not significantly different as compared to the control group. In conclusion, VLCKD induces the activity of LAL in morbidly obese subjects and reduces the secretion of all circulating lipoproteins. These effects could be attributed to the peculiar composition of the diet, which is particularly poor in carbohydrates and relatively rich in proteins.

Impact of volunteer-related and methodology-related factors on the reproducibility of brachial artery flow-mediated vasodilation

Brachial artery flow-mediated dilation (FMD) is a popular technique to examine endothelial function in humans. Identifying volunteer and methodological factors related to variation in FMD is important to improve measurement accuracy and applicability. Volunteer-related and methodology-related parameters were collected in 672 volunteers from eight affiliated centres worldwide who underwent repeated measures of FMD. All centres adopted contemporary expert-consensus guidelines for FMD assessment. After calculating the coefficient of variation (%) of the FMD for each individual, we constructed quartiles (n = 168 per quartile). Based on two regression models (volunteer-related factors and methodology-related factors), statistically significant components of these two models were added to a final regression model (calculated as β-coefficient and R). This allowed us to identify factors that independently contributed to the variation in FMD%. Median coefficient of variation was 17.5%, with healthy volunteers demonstrating a coefficient of variation 9.3%. Regression models revealed age (β = 0.248, P < 0.001), hypertension (β = 0.104, P < 0.001), dyslipidemia (β = 0.331, P < 0.001), time between measurements (β = 0.318, P < 0.001), lab experience (β = -0.133, P < 0.001) and baseline FMD% (β = 0.082, P < 0.05) as contributors to the coefficient of variation. After including all significant factors in the final model, we found that time between measurements, hypertension, baseline FMD% and lab experience with FMD independently predicted brachial artery variability (total R = 0.202). Although FMD% showed good reproducibility, larger variation was observed in conditions with longer time between measurements, hypertension, less experience and lower baseline FMD%. Accounting for these factors may improve FMD% variability.

α1-Adrenoreceptor activity does not explain lower morning endothelial-dependent, flow-mediated dilation in humans

Early morning reduction in endothelium-dependent, flow-mediated dilation (FMD) may contribute to the high incidence of sudden cardiac death at this time of day. The mechanisms underpinning diurnal variation in FMD are unclear, but potentially relate to a circadian rhythm in sympathetic nerve activity. We hypothesized that blockade of α(1)-mediated sympathetic nerve activity would act to attenuate the diurnal variation in FMD. In a randomized and placebo-controlled design, we measured brachial artery FMD in 12 participants (mean age = 26 yr, SD = 3) at 0600 and 1600 after ingestion of an α(1)-blocker (prazosin, 1 mg/20 kg body mass) or placebo. Arterial diameter and shear rate were assessed using edge-detection software. Heart rate and blood pressure were also measured. Data were analyzed using linear mixed modeling. Following placebo, FMD was 8 ± 2% in the morning compared with 10 ± 3% in the afternoon (P = 0.04). Blockade with prazosin led to a slight but nonsignificant increase in morning FMD (P = 0.24) and a significant (P = 0.04) decrease in afternoon FMD, resulting in no diurnal variation (P = 0.20). Shear rate did not differ in the morning or afternoon under either condition (P > 0.23). Blood pressure was lower following prazosin compared with placebo (P < 0.02), an effect that was similar at both times of day (P > 0.34). Heart rate and norepinephrine levels were higher in the afternoon following prazosin. These data indicate that α(1)-adrenoreceptor activity does not explain lower morning endothelium-dependent FMD.

Influence Of Measures Of Body Composition On Vascular Function In Children.

Brachial artery flow mediated dilation (FMD) has become a commonly applied technique for the assessment of vascular health in humans. Although shear stress and artery size are acknowledged determinants of the FMD response, recent studies suggest that FMD is also governed by other factors. PURPOSE: To investigate the relationships between vascular function and body composition variables in children. METHODS: FMD (FMD%) was recorded and then normalised for the stimulus shear rate (FMD/SRAUC) in 129 healthy children (75 female; 10.3±0.3 yrs; 54 male; 10.4±0.3yrs). Body composition variables (mass, lean mass and fat mass in the whole body, arm and forearm) were assessed by DEXA. Bivariate correlations explored the association between FMD%, FMD/SRAUC and body composition variables. A stepwise multiple linear regression investigated the relative contribution of baseline diameter, SRAUC and body composition variables to FMD%. RESULTS: FMD% significantly (p<0.05) correlated with arm fat mass (r=-0.18) and forearm fat mass (r=-0.201). FMD/SRAUC significantly correlated with whole body mass (r=-0.26), whole body fat mass (r=-0.24), arm mass (r=-0.25), arm fat mass (r=-0.28), forearm mass (r=0.194) and forearm fat mass (r=0.211). Baseline artery diameter accounted for 13.5 % of the variation in FMD%, while shear rate stimulus and body composition variables did not significantly contribute to FMD% prediction. Significant correlations were observed between baseline artery diameter and whole body mass (r=0.21), whole body lean mass (r=0.28), arm mass (r=0.23), arm lean mass (r=0.32), forearm mass (r=0.24) and forearm lean mass (r=0.31). CONCLUSIONS: Significant correlations were observed between FMD%, FMD/SRAUC and measures of total and fat mass suggestive that fat mass has a negative association with vascular health. Although whole body and segmental body composition variables exert a relatively weak influence with regard to the determination of vascular function in children, further research might focus on the utility of ratio and allometric scaling procedures to explain the magnitude of the FMD response.

Heritability of flow-mediated dilation: a twin study.

Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker for early atherosclerotic vascular disease and future cardiovascular events. To estimate the heritability of brachial artery FMD using a twin design. We estimated the heritability of FMD using 94 middle-aged male twin pairs. FMD was measured by ultrasound, and traditional coronary heart disease risk factors were measured. Genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in FMD. The mean age of the twin participants was 54.9 +/- 2.8 years. The mean FMD was 0.047 +/- 0.030. The intraclass correlation coefficient was higher in MZ twins [0.38, 95% confidence interval (CI) 0.32-0.43] than in DZ twins (0.19, 95% CI 0.11-0.26), suggesting a role of genetic influence in FMD variation. Structural equation modeling showed that both genetic and unique environmental factors contributed significantly to the variation in FMD. The crude FMD heritability was 0.37 (95% CI 0.15-0.54). After adjustment for traditional cardiovascular risk factors, including age, total cholesterol, blood pressure, and body mass index, the heritability of FMD was 39% (95% CI 0.18-0.56). The remaining variation in FMD could be explained by individual-specific environment. This is the first study using twins to estimate the relative contributions of genetics and environment to the variation in FMD in a US population. Our results demonstrate a moderate genetic effect on brachial artery FMD, independent of traditional coronary risk factors. Our data also highlight the importance of unique environment on the variability in FMD.

Intensity of Lipid Lowering With Statins and Brachial Artery Vascular Endothelium Reactivity After Acute Coronary Syndromes (from the BRAVER Trial)

The time course and differential effects of statin regimens on endothelial function after acute coronary syndromes (ACSs) are unknown and could contribute to the superiority of a more intense strategy. A subset of subjects who were enrolled in the PROVE IT-TIMI 22 trial (n = 50) underwent evaluation of vascular reactivity by high-resolution brachial ultrasound. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent sublingual nitroglycerin-mediated dilation (NMD) were measured at baseline and at 48 hours, 1 month, and 4 months after the initiation of 40 mg of pravastatin (n = 26) or 80 mg of atorvastatin (n = 24). After 4 months, low-density lipoprotein cholesterol was decreased by 32% in the atorvastatin group but was not different from baseline after ACS in the pravastatin group. C-reactive protein decreased similarly in the 2 groups. Brachial artery diameters at rest were similar in the 2 groups and at each time point of the trial. FMD and NMD increased significantly after 4 months by 27% and 24%, respectively (p <0.05), with no difference between groups. There was no correlation between the change in FMD and the change in lipids or C-reactive protein. In subjects who had received previous statin therapy (n = 15), there was no significant variation in FMD (p = 0.140) and NMD (p = 0.129). In conclusion, initiation of statin therapy soon after ACS is associated with improvements in endothelium-dependent and independent vascular reactivities after 4 months.

The Variation Of Flow Mediated Dilation During Morning Hours

Flow Mediated Dilation (FMD) in response to reactive hyperemia has been established as a non-invasive measurement of endothelial function. There are many confounding variables, including diurnal variation, diet, sleep and physical activity, which have an effect on the measurement of FMD; these variables appear to be easiest to control during morning hours. A period of non variable FMD measurements is needed to investigate the acute effects of an intervention. The stability of FMD during the morning hours is unknown, thus the hypothesis that morning hours will be the most stable time period for FMD needs to be investigated. PURPOSE The purpose of this study was to investigate the variability of FMD during a two-hour period in the morning. METHODS The examination of brachial artery FMD in response to reactive hyperemia by high resolution ultrasound was performed in 12 healthy college students (4 men, 8 women), age 24.7±3.4 yrs; every 30 min from 0800 to 1000 hrs (5 measurements). Each subject was instructed to 1) fast for 12 hrs, 2) abstain from exercise for 12 hrs and 3) awake between 0600–0700 hrs, all prior to testing. vessel diameters were measured by two independent technicians (intra-class correlation coefficient of .9768). Regression analysis was used to calculate the slope and standard error of estimate (SEE) for descriptive analysis for each subject. One-way ANOVA with repeated measures was used to compare FMD of the five time periods. RESULTS Mean slope and mean SEE were .015 and 1.71%, respectively. No significant differences (p>.05) in FMD were found between each of the five measurements (p=.415). Mean FMD ± SD were 9.89±3.27%, 10.77±2.51%, v9.84±2.21%, 9.30±2.19%, 10.64±3.44% at 0800, 0830, 0900, 0930 and 1000 hrs, respectively. CONCLUSION These results suggest that there is minimal variation in FMD during a two-hour morning period in healthy college students. Therefore, when the acute effects of an intervention are investigated, post intervention measurements can be compared to baseline measurements when taken in the same two-hour morning period.

Biological correlates of day-to-day variation in flow-mediated dilation in individuals with Type 2 diabetes: a study of test-retest reliability.

Dysfunction of the vascular endothelium is commonly observed in Type 2 diabetes, and endothelial function may be an important outcome for clinical trials in diabetic samples. However, the most commonly used non-invasive test of endothelial function (flow-mediated dilation [FMD]) is technically challenging to perform, and no previous studies have carefully examined the reproducibility of FMD measurements in individuals with Type 2 diabetes. In this study, we tested the hypothesis that larger day-to-day changes in insulin and glucose are associated with larger fluctuations in FMD. Ultrasound was used to measure the FMD (% change from baseline diameter) of the brachial artery in 18 healthy adults with Type 2 diabetes on three separate occasions, in the absence of changes to diet, activity level or medications. The CV and mean deviations between pairs of FMD scores in the same individual were used as the primary outcome variables. The CV for FMD (29.7%) was higher than the level traditionally accepted for biochemical assays. However, this CV estimate is within the low range of published values for FMD in healthy individuals. FMD scores were not significantly correlated with glucose or insulin levels. However, subjects with the largest variability in FMD also showed the largest fluctuations in glucose ( r=0.52), insulin ( r=0.47) and heart rate ( r=0.48) ( p</=0.05). FMD can be reliably measured in individuals with Type 2 diabetes, and population-specific data on reliability is critical for the design of adequately powered studies of endothelial function.