Interobserver and intraobserver variability of flow-mediated vasodilatation of the brachial artery

Flow-mediated endothelial-dependent vasodilatation (FMD) of the brachial artery is a method capable of detecting endothelial dysfunction. In order to implement this method in future clinical research studies, its reproducibility and precision have to be assessed. The aim of the study is to evaluate the inter- and intraobserver variability of FMD performed in our department. We investigate 40 patients. FMD is measured by two independent observers to test the interobserver variability, and repeated by the first observer to test the intraobserver variability. We compare the baseline and post-ischemic diameter of the brachial artery and the percent dilatation. The correlation coefficients for these comparisons are high (>0.92) with a significance of less than 0.001. The inter- and intraobserver variability is further tested comparing the mean values of the baseline and post ischemic diameter of the brachial artery and the percent dilatation. The absolute values of the mean paired differences and the standard deviations (SDs) of the differences are 0.02850 +/- 0.05942, P = 0.004, 0.01175 +/- 0.08177, P = 0.369 and 0.28375 +/- 1.61561, P = 0.273, respectively for the interobserver variability and 0.00475 +/- 0.04663, P = 0.523, 0.00050 +/- 0.05267, P = 0.952 and 0.15725 +/- 1.19922, P = 0.412, respectively for the intraobserver variability. It can be concluded that the inter- and intraobserver variability for FMD performed in our department is acceptable. FMD can be performed precisely and accurately, with a satisfactory reproducibility and can be safely and reliably implemented in future clinical research studies.     

Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing's Syndrome

Background Cushing’s Syndrome (CS) is associated with excess and premature cardiovascular disease. Endothelial dysfunction is the initiating event in the development of atherosclerosis. Endothelial function is assessed by flow-mediated dilatation (FMD) of brachial artery. The aim of this study was to assess FMD in patients with CS. Methods We prospectively evaluated 22 patients with CS (12 women, 10 men; aged 42 ± 11 years, serum cortisol 28.2 ± 14 μg/dl, 24-h urinary free cortisol (UFC) 269 ± 92 μg/day), and 23 control subjects (13 women, 10 men; aged 43 ± 10 years, serum cortisol 14 ± 4 μg/dl, 24 h cortisol 60 ± 22 μg/day). Endothelial function, measured as FMD of the brachial artery using ultrasound, was calculated in two groups. Endothelial function was evaluated by assessing 1-min postischemic FMD of the brachial artery. Results FMD was lower in patients with CS than that in those without (11.7 ± 4.8% vs. 15.8 ± 3.2%, P = 0.0001, respectively). There was no significant difference between two groups regarding baseline diameter of brachial artery. But, hyperemia diameter was lower in patients with CS than without CS (3.6 ± 0.22 mm vs. 3.9 ± 0.19 mm, P = 0.04, respectively) Conclusion Endothelium-dependent FMD may impair in patients with CS compared to controls. Measurement of endothelial function may identify high-risk individuals early and therapy to reduce or retard endothelial dysfunction in patients with CS may lead to decreased cardiovascular morbidity and mortality.     

A multicenter study design to assess the clinical usefulness of semi-automatic measurement of flow-mediated vasodilatation of the brachial artery

Flow-mediated vasodilatation of the brachial artery (FMD) is a marker which is related to endothelial nitric oxide bioavailability. Commercially available ultrasound machines equipped with online computer-assisted semi-automatic analysis software to measure FMD have recently become available in Japan. These devices enable more convenient examination, enhanced reproducibility of FMD measurement, and a shortened examination time. Using such devices, in the present multicenter prospective study we propose to: 1) establish standardized FMD values and determine the annual rates of FMD change in healthy subjects; 2) confirm the predictive value of FMD for future cardiovascular events in Japanese subjects; 3) evaluate the potential usefulness of a multimarker strategy, including measurements of FMD, pulse-wave velocity (PWV), ankle-brachial pressure index, biochemical markers, and proteomic biomarkers obtained by mass spectroscopic analysis to assess the prognosis of subjects with coronary artery disease; and 4) clarify the usefulness of FMD measurement to predict the rate of progression of carotid atherosclerosis, arterial stiffness and microalbuminuria in subjects with hypertension or diabetes mellitus. In total, we estimate that approximately 4000 Japanese subjects in 3 different study groups will eventually be enrolled in this prospective observational investigation. We anticipate that the present study will provide important evidence for the usefulness of FMD measurement in the risk stratification for cardiovascular disease.     

Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men

Endothelial dysfunction has been reported to be the initial step in atherosclerosis. A noninvasive technique that uses ultrasound to measure the intima-media thickness of the carotid artery has been applied to evaluate localized atherosclerosis. This study was undertaken to elucidate whether endothelial dysfunction in the brachial artery is related to the intima-media thickness of the carotid artery. Thirty-four men with atherosclerosis (mean+/-SE age 61+/-2 years) and 33 age-matched men without clinical atherosclerosis were examined. The intima-media thickness and plaque formation of the common carotid artery were assessed by B-mode ultrasonography. We also noninvasively measured brachial artery diameter by the same ultrasound machine when the subjects were at rest, during reactive hyperemia, which causes endothelium-dependent vasodilatation, and after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. The atherosclerosis group had a significantly greater intima-media thickness of the common carotid artery than did the control group (1. 02+/-0.04 versus 0.91+/-0.03 mm, P<0.05). The flow-mediated diameter (FMD) increase (percent FMD=DeltaD/D x 100) in the atherosclerosis group was significantly smaller than that in the control group (2. 8+/-0.4% versus 5.1+/-0.6%, P<0.01). A significant negative correlation between the intima-media thickness of the carotid artery and percent FMD was found in all of the subjects. On multiple regression analysis, percent FMD showed a significant negative correlation with the intima-media thickness of the common carotid artery. These findings support the concept that endothelial dysfunction is significantly related to atherogenesis.     

Characteristics of flow-mediated brachial artery vasodilation in human subjects

In an effort to determine whether arterial conductance vessels dilate in response to increased blood flow stimuli, brachial artery area (cm2) and diameter (cm) were derived by simultaneous measurement of forearm blood flow (ml/min.100 ml) and brachial artery blood flow velocity (cm/sec) following the release of arterial occlusion. Measurements were made at rest and at the time of maximal flow after the release of graded periods of forearm arterial occlusion (20 seconds to 10 minutes). These studies showed a graded large vessel dilation following occlusions of up to 1 minute (baseline diameter, 0.33 +/- 0.01; after 1 minute occlusion, 0.45 +/- 0.02 cm; p less than 0.05) after which time diameter plateaued (after 10 minutes of occlusion, 0.48 +/- 0.02 cm). In addition, the time course of diameter and flow changes after 3 minutes of arterial occlusion were examined. Flow was maximal at 5 seconds but diameter was maximal at 15-30 seconds after release. Furthermore, the half time for the return of diameter to baseline was longer than that for blood flow. We also measured the diameter after forearm heating (42 degrees C) and noted a substantial increase in diameter (before heating, 0.32 +/- 0.01; after heating, 0.39 +/- 0.02 cm; p less than 0.05). Finally, we applied pressure to the venous side of arteriovenous fistulae in five hemodialysis patients. This maneuver was associated with large reductions in forearm blood flow (baseline flow, 63.3 +/- 10.6; venous compression flow, 36.0 +/- 4.4 ml/min.100 ml; p less than 0.05) and a decrease in brachial artery size (baseline diameter, 0.63 +/- 0.07; venous compression diameter, 0.58 +/- 0.06 cm; p less than 0.05). We conclude that 1) the human brachial artery size changes in response to changes in blood flow, and 2) the maximal dilation occurs after maximal flow is noted. Although alternate explanations are possible for each of our observations, our results are most consistent with a flow-mediated, localized vasodilating process.     

Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery.

OBJECTIVES: We examined whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading. BACKGROUND: Endothelial dysfunction has been shown to occur in patients with diabetes mellitus (DM), and chronic hyperglycemia is implicated as a cause of endothelial dysfunction. However, in many patients with Type 2 DM and in those with impaired glucose tolerance (IGT), fasting blood glucose may be within normal limits, and hyperglycemia occurred only post-prandially. METHODS: With ultrasound technique, we measured flow-mediated endothelium-dependent vasodilation during oral glucose tolerance test in 58 subjects: (17 patients with normal glucose tolerance [NGT], 24 with IGT, and 17 with type 2 DM). In addition, we measured the levels of thiobarbituric acid reactive substances (TBARS) and nitrite/nitrate. RESULTS: Flow-mediated vasodilation decreased after glucose loading (NGT: 7.53+/-0.40, 4.24+/-0.28 and 6.35+/-0.40, in fasting, at 1- and 2-h, respectively, IGT: 6.50+/-0.48, 1.40+/-0.41** and 4.00+/-0.47*, respectively; DM: 4.77+/-0.37, 1.35+/-0.38** and 1.29+/-0.29%**, respectively; *p < 0.01 vs. fasting, **p < 0.005 vs. fasting). The TBARS concentration increased in parallel with plasma glucose level in each group (NGT: 1.43+/-0.07, 2.03+/-0.12 and 1.80+/-0.12, respectively; IGT: 1.65+/-0.11, 2.46+/-0.12** and 1.94+/-0.08*, respectively; DM: 1.73+/-0.07, 2.34+/-0.08** and 2.47+/-0.09** nmol/ml, respectively; *p < 0.05 vs. fasting, **p < 0.01 vs. fasting). Glucose loading did not change nitrite/nitrate concentration in any of the groups. CONCLUSIONS: Hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis.     

Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease

Acute administration of high-dose testosterone in men with coronary artery disease improves endothelial function.     

原发性高血压患者肱动脉流量介导的舒张活性变化

目的:探讨原发性高血压(EH)患者内皮依赖性血管舒张功能的改变。方法:应用无创性高分辨率超声检测61例EH患者(EH组)和38例正常血压者(对照组)肱动脉流量介导的舒张(FMD)活性,以评价其血管内皮功能。结果:①对照者、Ⅰ级EH者、Ⅱ级EH者的FMD呈逐渐明显降低(P<0.05或<0.01)。②Ⅰ级、Ⅱ级EH组的FMD峰值时间较对照组均明显延迟(分别P<0.05和<0.01)。结论:EH患者存在着明显的内皮功能障碍,并随着病程进展损害逐渐加重。     

Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events

The aim of this pilot study was to test the prognostic value of serial measurements of peripheral endothelial function, assessed by brachial artery flow-mediated dilation (FMD), in patients with angiographically proven coronary artery disease. In 68 patients, FMD was measured on the day after coronary angiography and again after a mean of 14 +/- 12 months. Patients were divided into two groups: absolute improvement in FMD > or = 3% (FMD-improver = FMD-i) and < 3% (FMD-non-improver = FMD-ni). After a mean follow-up of 44 +/- 12 months, cardiovascular events were recorded. Baseline characteristics were similar between groups, except the number of risk factors which was smaller in FMD-i (1.6 +/- 0.7 vs 2.1 +/- 0.9, p < 0.02). Cardiovascular events were more frequent in FMD-ni (9 vs 1 event; p < 0.05). In Kaplan-Meier analysis, a trend towards a better outcome in patients with improved FMD was found using the log-rank test (p = 0.08). The single baseline FMD showed no relationship with late cardiovascular events. Thus, 'delta-FMD' may be more closely related to prognosis than a single FMD measurement.     

Reduced flow-mediated vasodilation of brachial artery in children with primary snoring

Background

Sleep disordered breathing, especially obstructive sleep apnea, is associated with endothelial dysfunction in both adults and children. However, the role of primary snoring (PS) on endothelial function has not been investigated. This study aimed to examine flow-mediated vasodilation (FMD) in both normal weight and overweight children with PS.

Methods

Children aged 6–18 years with habitual snoring were recruited from our sleep disorder clinic. Non-snoring controls were recruited from participants of a community growth survey. All subjects underwent polysomnography and FMD evaluation on the same day. Children with body mass index of greater than the 85th percentile of the local reference were defined as overweight. Subjects were divided into groups of normal weight, overweight, non-snorers and PS for comparisons.

Results

Two hundred and one children, of whom 83 were overweight, with a mean ± SD age of 11.3 ± 2.7 years were recruited. Seventy three out of 201 children had PS. Both normal weight (7.9 ± 1.3 vs. 8.5 ± 0.9, p = 0.012) and overweight subjects (7.4 ± 1.4 vs. 8.1 ± 1.1, p = 0.006) with PS had significantly reduced FMD than the non-snoring controls. Multivariate linear regression model showed that PS was independently associated with reduced FMD in both normal weight (p = 0.014) and overweight subgroups (p = 0.016) after controlling for obstructive apnea hypopnea index.

Conclusions

PS in children is associated with reduced FMD, independent of obesity.     

Prognostic role of flow-mediated dilatation of the brachial artery in hypertensive patients

BACKGROUND: The prognostic role of endothelial dysfunction, as evaluated by flow-mediated vasodilatation of the brachial artery, has been demonstrated in patients at very high risk. We aimed to investigate whether flow-mediated vasodilatation predicts cardiovascular events in uncomplicated hypertensive patients. METHODS AND RESULTS: A total of 172 prospectively identified uncomplicated hypertensive patients (age 56 +/- 8 years, 41% women, 48 with diabetes mellitus type 2) were studied. At baseline all patients were untreated and underwent baseline standard laboratory examination. A standard echocardiogram was performed for the evaluation of left ventricular anatomy and function and patients with systolic dysfunction or left ventricular wall motion abnormalities were excluded. Endothelial function was measured as flow-mediated vasodilatation of the brachial artery using high-resolution ultrasound. Patients were followed for 95 +/- 37 months (range 2-136 months). A first nonfatal or fatal cardiovascular event occurred in 32 patients. The incidence of cardiovascular events was 1.4 and 3.1 per 100 patient-years in patients with a flow-mediated vasodilatation below and above the median value (4.7%), respectively (P < 0.005 by the log-rank test). In Cox analysis, controlling for age, sex, glycemia, cholesterol, smoking, BMI, systolic and diastolic blood pressure at baseline and left ventricular mass index, a low flow-mediated vasodilatation conferred an increased risk of cardiovascular events (odds ratio 2.67, 95% confidence interval 1.17 to 6.1, P = 0.02). CONCLUSION: The presence of endothelial dysfunction, as evaluated by flow-mediated vasodilatation of the brachial artery, identifies hypertensive patients at increased risk of nonfatal and fatal cardiovascular events.     

Correlation of endothelial dysfunction measured by flow-mediated vasodilatation to severity of coronary artery disease

ObjectivesBrachial artery ultrasound imaging during reactive hyperemia is widely used tool for quantifying endothelium dependent vasomotion. Angiodefender device is used for non invasive determination of percentage flow mediated vasodilation (FMD). An attempt is made to study whether endothelial dysfunction determined by FMD of brachial artery predicts the presence or absence of coronary artery disease and its correlation with the severity of coronary artery disease.MethodsOne hundred six patients admitted between May 2014 and April 2015 who were posted for coronary angiography diagnosed to have chronic stable angina on clinical basis and/or by exercise stress test, for evaluation of coronary artery disease were submitted to standard clinical evaluation, calculation of percentage FMD by Angiodefender device. Statistical significance of difference of categorical variables was tested using Fisher’s exact test. Sensitivity, specificity, positive predictive value and negative predictive value of FMD were studied.ResultsThere was no correlation between number of risk factors and percentage of FMD. Significantly higher proportion of cases with less FMD had higher prevalence of coronary artery disease and vice-versa. Significantly higher proportion of cases with positive stress test had less percentage of FMD and vice-versa. Significantly higher proportion of cases with less percentage of FMD and positive stress test had higher prevalence of obstructive coronary artery disease and vice-versa. Specificity was 100% when percentage of FMD was ≤10.ConclusionsFMD an inexpensive and non-invasive test provides information regarding extent and severity of coronary artery disease.     

肱动脉血流介导的舒张功能与冠状动脉病变的关系

目的:观察冠心病(CHS)患者肱动脉血流介导的舒张功能与冠状动脉(冠脉)病变之间的关系。方法:选择冠脉造影(CAG)患者107例,根据cAG结果分为冠脉正常组28例、冠脉早期病变组31例、CHD组48 例,CHD组采用Gensini评分进一步分为轻度病变(1-20分)26例,重度病变(≥20分)22例。在CAG前24 h 内应用高分辨率超声检测肱动脉血流介导的舒张功能,与CAG结果作对照分析。结果:CHD组中轻度病变与重度病变者较冠脉早期病变组及冠脉正常组的肱动脉内皮依赖的舒张功能(EDD)明显降低[(4．75±0．94)％、 (3．67±1．01)％:(5．98±0．89)％、(6．15±0．97)％,P<0．05或0．01];重度冠脉病变者EDD较轻度冠脉病变者明显下降[(3．67±1．01)％:(4．75±0．94)％,P<0．05]。而硝酸甘油介导的血管扩张功能(非EDD)在各组间差异无统计学意义(P>0．05)。肱动脉EDD与冠脉病变积分呈负相关(r=0．72,P<0．01)。结论: CHD患者常存在肱动脉EDD受损,肱动脉EDD可间接反映冠脉病变程度。     

Relevance of homocysteine on brachial flow-mediated vasodilatation and carotid and femoral intima-media thickness in patients with hypercholesterolemia

The relevance of homocysteine to brachial flow-mediated vasodilatation and carotid and femoral intima-media thickness was investigated in 192 patients with hypercholesterolemia. Low-density lipoprotein cholesterol and homocysteine levels predicted brachial flow-mediated vasodilatation, internal carotid mean intima-media thickness, and intima-media thickening at all femoral sites. Homocysteine levels seem to be an additional factor in the initial atherosclerotic damage of patients with hypercholesterolemia.     

Measurement of flow-mediated vasodilation of the brachial artery: a comparison of measurements in the seated and supine positions.

BACKGROUND: Measurement of flow-mediated vasodilation (FMD) is used to assess endothelial function in humans and according to the guidelines, subjects must remain supine during the study. However, measurement of FMD while seated would be more comfortable and convenient for patients, so the purpose of this study was to determine the effect of the patient's position on FMD results. METHODS AND RESULTS: High-resolution ultrasonography, a linear array transducer (13 MHz) and an arm-holding device were used to measure arterial diameter in response to reactive hyperemia (FMD, cuff inflated to 50 mmHg above systolic blood pressure for 5 min) and in response to sublingual nitroglycerine (NTG, 75 microg) in 31 subjects, which included those with cardiovascular diseases. There was no significant difference between basal or peak hyperemic blood flow in the seated or supine position. Basal brachial artery diameter, FMD and vascular response to NTG were similar in both positions (basal diameter: 3.8+/-0.4 vs 3.9+/-0.4 mm, FMD: 7.3+/-4.3% vs 7.2+/-4.5%, NTG: 13.1+/-5.1% vs 12.8+/-5.6%). CONCLUSIONS: The findings suggest that measurement of FMD in the seated position is as useful as measuring it in the supine position for assessing endothelial function. This flexibility of position is better for patients and physicians, and should lead to more widespread measurement of FMD.