Non-invasive assessment of brachial artery endothelial vasomotor function: the effect of cuff position on level of discomfort and vasomotor responses

Non-invasive assessment of brachial artery flow-mediated dilation using cuff occlusion of the arm above or below the elbow to stimulate flow is emerging as a highly useful technique to examine endothelial vasomotor function in human subjects. In anticipation of a large-scale investigation, an important issue is the acceptability of the technique to participants. The purpose of this study was to determine the level of discomfort associated with the technique and compare it to the commonly used procedure of venipuncture. Flow-mediated dilation was determined using cuff occlusion of the arm above the elbow and a blood sample was obtained by standard venipuncture from 54 subjects. The level of discomfort for each procedure was assessed and compared using a visual analogue scale and was found to be extremely low. When the occlusion cuff was positioned above the elbow, the discomfort was slightly more severe (1.9+/-1.9 cm) than venipuncture (1.0+/-1.3 cm, p = 0.003). In 27 subjects, the effect of cuff position (above or below the elbow) was compared: the below the elbow position was associated with a reduction in the percentage increase in flow (570+/-280% versus 900+/-560%, p = 0.005), flow-mediated dilation (6.8+/-3.8% versus 9.8+/-5.7%, p = 0.008) and discomfort (1.6+/-0.8 versus 3.7+/-2.2 cm, p = 0.008). When the cuff was located below the elbow, the level of discomfort was equivalent to that associated with venipuncture. Thus, non-invasive assessment of flow-mediated brachial artery dilation is well tolerated and appears to be suitable for a large-scale study of endothelial function.     

L-精氨酸对肱动脉内皮功能的改善作用

目的:探讨L-精氨酸(L-Arg)对人血管内皮功能的影响。方法:以高分辨率超声对住院患者行肱动脉内皮功能测定,血流介导的肱动脉内径变化率(FMD%)被用来评估血管内皮功能,硝酸甘油诱发的血管扩张(NMD%)被用来反映血管平滑肌功能。以38例存在肱动脉内皮功能不全的住院患者为研究对象,分为2组,静脉滴注L-Arg(A组)及口服L-Arg(B组)。2组治疗2周后复查FMD%及NMD%。比较治疗前后FMD%及NMD%的变化,同时比较2组肱动脉内皮功能有无差异。结果:2组治疗后FMD%高于治疗前,治疗前后比较FMD%差异有统计学意义(P<0.01);而2组治疗前后NMD%差异无统计学意义(P>0.05)。结论:静脉滴注和口服L-Arg均具有改善肱动脉内皮功能的作用,疗效无明显不同。     

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.     

Effect of smoking on endothelial function and wall thickness of brachial artery.

BACKGROUND: Impaired flow mediated dilatation (FMD) and increased wall thickness (WT) of the brachial artery have been associated with atherosclerosis and its risk factors. In this study we sought to determine brachial artery wall thickness in chronic smokers and the instantaneous effect of smoking on brachial artery endothelium dependent vasodilator function in smokers and non-smokers. METHOD AND RESULTS: Using a high-resolution ultrasound, WT of posterior brachial artery wall, the diameter of brachial artery at rest and during reactive hyperemia (FMD %), as well as after sublingual administration of nitroglycerine (nitroglycerine mediated dilatation (NMD) %) was measured in 20 smokers and 20 non-smokers. Wall thickness (WT) of the posterior brachial artery wall and the wall index (WI) were greater in smokers than non-smokers. The baseline brachial artery diameter was comparable in smokers and non-smokers. Flow mediated dilation (FMD) was found to be less in smokers than non-smokers. The NMD in smokers also did not differ significantly from that in non-smokers. Flow mediated dilation significantly reduced after smoking compared to baseline in both groups. However, NMD remained unchanged after smoking in both groups. CONCLUSIONS: Increased WT and impaired endothelium-dependent dilatation of brachial artery suggests that cigarette smoking disrupts vessel wall morphology long before atherosclerosis is manifest.     

糖代谢异常对肱动脉内皮舒张功能影响的研究

目的 探讨葡萄糖代谢异常对肱动脉血管内皮舒张功能的影响.方法 应用高分辨率超声测量39例糖耐量减低(IGT)、47例T2DM和44例糖耐量正常者(NGT)反应性充血前后及含服硝酸甘油后肱动脉内径的变化.结果 IGT、T2DM组肱动脉内皮舒张功能均受损,T2DM组、NGT组分别与IGT组比较,差异有统计学意义(P＜0.05),T2DM组较NGT组差异明显(P＜0.01).与NGT组比,IGT组、T2DM组FPG、 HbA1c、LDL-C升高,与内皮依赖性血管舒张功能(EDVR)负相关;HDL-C降低,与EDVR正相关(P均＜0.01).结论 葡萄糖代谢异常可对肱动脉内皮舒张功能造成损伤.     

The acute effect of aerobic exercise on brachial artery endothelial function in renal transplant recipients

This study compared the effect of a 30-minute walk on brachial artery endothelial vasodilatation in kidney transplant (KT) recipients and healthy controls (HCs). Endothelial-dependent vasodilatation was measured by ultrasound before and after exercise. The HCs experienced a significant increase in vasodilatation after exercise 1 minute postocclusion when compared with the KT recipients (22%+/-13% vs 3%+/-4%; P<.05). Also, the HCs had a significantly higher vasodilatation from pre-treadmill walk to post-treadmill walk (1 minute postocclusion) when compared with KT recipients (from 3%+/-6% to 22%+/-13% vs 1%+/-3% to 3%+/-4%; P<.05). This acute vasodilatory response observed in the HCs may be related to the immediate release of nitric oxide and the combined response to shear stress and exercise. The KT recipients had several coronary artery disease risk factors that may have adversely affected endothelial function.     

青年长期吸烟者血管内皮依赖性舒张功能的改变

目的:探讨青年长期吸烟血管内皮依赖性舒张功能的改变。方法:测定20例长期吸烟青年及15例正常对照者血流介导的和硝酸甘油介导的肱动脉内径改变。结果:两组肱动脉内径基础值(3.75±0 61mm:3.81±0.55mm)及硝酸甘油介导的肱动脉舒张[(22.13±7.65)％:(23.45±8.21)％]无显著差异(P>0.05),而血流介导的血管扩张存在显著差异.为[(3.61±2.90)％:(8.32±4.75)％]、P<0.01。单因素相关分析表明,肱动脉内皮依赖件舒张与吸烟量呈显著负相关(r=0.523.P<0.001).结论:青年长期吸烟者血管内皮依赖性舒张功能明显受损,受损程度与吸烟量有关。     

Reproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function

Abstract Background : High-resolution brachial artery ultrasonography is used to study vasodilator response induced by physiologic reactive hyperaemia. We examined the reproducibility of measuring flow-mediated dilatation (FMD) on two occasions.
Aims : To determine the degree of variability of this technique in our vascular laboratory for the design of clinical research studies.
Methods : Nineteen subjects were studied on two separate occasions using an Acuson 128 ultrasound device and a 7.0 MHz linear array transducer. Reactive hyperaemia was induced in the brachial artery by inflation and release of a blood pressure cuff. Nitrate-induced dilatation was assessed in 11 of the 19 subjects. Measurements were made by two observers blinded to subject details.
Results : The 11 subjects given sublingual GTN during the first ultrasound study had a mean nitrate-induced dilatation of 20.7% (sd 9.6). The mean vessel diameter of 3.78 mm (sd 0.7) at rest and 3.89 mm (sd 0.7) during reactive hyperaemia yielded a mean FMD of only 3.0% (sd 2.7). The mean difference in FMD within-observers was 0.13% (sd 2.07), between-observers 0.06% (sd 2.17) and between-studies was 0.57% (sd 6.83).
Conclusions : The reproducibility of FMD measured by brachial artery ultrasound was poor and likely to render the measurements inaccurate for clinical research in our hands. Between-study variation contributed the largest proportion of total study variability. We suggest that investigators using this technique conduct their own careful reproducibility studies in order to avoid the misinterpretation of 'negative' studies.     

Short- and long-term influence of diet and simvastatin on brachial artery endothelial function

BACKGROUND: Endothelium-dependent dilation (EDD) has often been studied in patients with hypercholesterolemia without overt coronary atherosclerosis where an improvement after statin treatment has been documented within few weeks. The aim of the study was to assess the short-term effect of diet as well as short- and long-term effect of simvastatin on EDD in patients with hypercholesterolemia and ischemic heart disease. METHODS: In 43 male patients with hypercholesterolemia and ischemic heart disease, EDD of the brachial artery was measured at baseline, after 3 months on a lipid-lowering diet, and after another 1, 3 and 12 months on simvastatin at 40 mg/day. RESULTS: Three months changes in EDD were neither influenced by diet nor short-term simvastatin therapy (4.9% vs. 4.9% vs. 4.8%, p=ns). Twelve months simvastatin treatment, however, significantly improved EDD by 32.7% (4.9% vs. 6.5%, p=0.007). By regression analysis an individual adjusted increase in EDD during the simvastatin treatment period was seen (coefficient 0.132 a month, p=0.002). A significant reduction in total cholesterol of 31.0% (6.1+/-0.8 vs. 4.2+/-0.7, p<0.001) and LDL cholesterol of 42.6% (4.0+/-0.8 vs. 2.2+/-0.6, p<0.001) was observed. CONCLUSION: EDD is improved after long-term simvastatin therapy; however, neither did 3 months diet or 3 months simvastatin therapy has influence on the EDD.     

厄贝沙坦氢氯噻嗪对肱动脉内皮功能及颈动脉内膜中层厚度的影响

目的观察厄贝沙坦氢氯噻嗪对高血压患者肱动脉内皮功能及颈动脉内膜中层厚度的影响。方法选择2010年6月~2013年2月在徐州医学院附属医院老年科就诊的1级、2级原发性高血压患者137例,完成本研究127例,随机分为氢氯噻嗪组60例及厄贝沙坦氢氯噻嗪67例。2组患者每日晨起分别口服氢氯噻嗪25 mg及厄贝沙坦氢氯噻嗪1片,连续12个月。检测2组患者治疗前后血压、血脂、高敏C反应蛋白(hs-CRP)等指标,以及肱动脉内皮依赖性舒张功能(EDD)和颈动脉内膜中层厚度(IMT)的变化。结果与治疗前比较,氢氯噻嗪组和厄贝沙坦氢氯噻嗪组治疗后收缩压[(156.49±9.10)mm Hg vs.(126.37±8.12)mm Hg,(157.26±8.91)mm Hg vs.(124.46±8.07)mm Hg]、舒张压[(98.73±5.54)mm Hg vs.(77.65±5.42)mm Hg,(99.54±5.38)mm Hg vs.(76.36±5.71)mm Hg]均降低,差异具有显著统计学意义(P均0.01)。与治疗前比较,厄贝沙坦氢氯噻嗪组患者治疗后内皮依赖性舒张功能[(5.37±0.91)%vs.(6.79±1.08)%,P0.01]提高,颈动脉内膜中层厚度[(1.16±0.25)mm vs.(1.03±0.20)mm,P0.05]降低。与氢氯噻嗪组患者治疗后比较,厄贝沙坦氢氯噻嗪组患者治疗后内皮依赖性舒张功能[(5.56±0.99)%vs.(6.79±1.08)%,P0.01]提高,颈动脉内膜中层厚度[(1.15±0.19)mm vs.(1.03±0.20)mm,P0.05]下降。结论厄贝沙坦氢氯噻嗪降压的同时可以改善肱动脉内皮功能、减少颈动脉内膜中层厚度。     

The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers

Abstract Background : Endothelial function is known to be abnormal in patients with diabetes and acute hyperglycaemia may play an aetiological role.
Aims : The aim of this randomised controlled study was to determine if acute systemic hyperglycaemia impairs endothelial function in normal subjects.
Methods : Endothelial function was assessed by the change in brachial artery diameter in response to forearm ischaemia using B-mode ultrasound in ten healthy subjects (eight male) aged 19–35 years. Brachial artery blood flow velocity and diameter were measured before and after five minutes of forearm ischaemia. Measurements were performed in the supine position after an overnight fast, before and after 60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two separate occasions at least 24 hours apart, and subjects were randomised to saline first or dextrose first. The largest diameter measured after ischaemia was divided by the resting arterial diameter to calculate percent dilatation of the artery from baseline, and is reported as flow-mediated dilatation (FMD).
Results : Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2 (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L p <0.002. Brachial artery blood flow velocity and diameter increased significantly from baseline after ischaemia ( p <0.002). Mean FMD (SEM) before and after infusion were not, however, significantly different ( p =0.4) (pre-saline 7.3 [1.0]%, post saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%).
Conclusions : These data suggest that acute hyperglycaemia does not impair FMD in normal subjects.     

Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility.

OBJECTIVE--To assess a non-invasive test for endothelial dysfunction, an important early event in the atherogenic process. METHODS--Using high resolution ultrasound, the accuracy of detecting small changes in vessel diameter was assessed using phantom "arteries", and the same equipment was then used to measure flow mediated dilatation in the brachial artery of 40 healthy adults aged 22-51 years, studied on four occasions; intervals between scans were 1-2 days, 1-2 weeks, and 2-4 months. RESULTS--Differences between pairs of phantom "arteries" with diameters 0.1-0.2 mm apart were correctly estimated in 162 of 264 cases (61%); no measurement by any of four independent observers was > 0.1 mm in error, and the mean error was 0.04 mm. For in vivo scans, the overall coefficient of variation for flow mediated dilatation was 1.8% (1.6% for women, 1.9% for men, P = 0.18). In 34/40 subjects (85%), all values for flow mediated dilatation were within 2.5% of the overall mean for each subject. A nested analysis of variance showed the expected between patient variability, and also significant day to day variation, but little between weeks or months. Using these data to generate power function analyses, we calculated that for individuals, an improvement in flow mediated dilatation of 4-8% is significantly greater than natural variability. In clinical trials, a mean improvement in flow mediated dilatation of at least 2% would usually be required to detect a treatment benefit, with much larger subject numbers needed for a parallel group compared to a crossover trial design. CONCLUSIONS--Vascular responses to endothelium dependent and independent stimuli in systemic arteries can be studied non-invasively in man. Subjects should be studied on at least two occasions before and after any intervention, to optimise the chance of showing a significant effect from any potentially beneficial therapy.     

高血压合并冠状动脉狭窄患者肱动脉内皮功能研究

目的:观察高血压合并冠心病患者血流介导的肱动脉扩张(FMD)的程度,探讨冠心病患者冠脉病变支数与FMD的关系。方法:选取在我科行冠脉造影检查的高血压患者160例。依据冠脉造影结果分为1、高血压合并冠心病组(冠心病组,98例),并依据冠脉造影(冠脉狭窄≥50%)再分为:①单支病变组(35例);②双支病变组(47例);③多支病变组(16例);2、高血压组(对照组,62例)。通过超声检测肱动脉基础状态,去压30秒、60秒的内径变化(FMD)。以Logistic回归分析:冠脉病变支数与FMD的关系。结果:冠心病组的FMD(7.41±0.73)显著小于高血压组的(10.51±0.68,P0.05)。冠心病单支、双支、多支病变组的FMD组间比较均有显著差异(P均0.05)病变支数越多,FMD越小,去压60秒的FMD为[单支病变组(7.01±0.29)、双支病变组(6.82±0.35)、多支病变组(6.09±0.29)。多元Logistic回归分析显示,与FMD关系密切的依次为冠状动脉多支病变去压后60秒(OR=3.158,P=0.000)、双支病变去压后30秒(OR=1.163,P=0.003)、单支病变去压后30秒(OR=1.076,P=0.004)。结论:高血压合并冠心病患者随着冠脉病变程度增加,动脉内皮功能损害就越重,呈负相关。检测血流介导的肱动脉扩张有助判断冠脉病变程度。     

Noninvasive assessment of endothelial dysfunction by brachial artery flow-mediated dilatation in prediction of coronary artery disease in Indian subjects

BACKGROUND: A noninvasive technique for testing endothelial function by ultrasound measurement of flow-mediated dilatation has recently generated considerable interest as a marker of atherosclerosis, and in the prediction of clinical coronary events and coronary artery disease. METHODS AND RESULTS: We measured the flow-mediated dilatation of the brachial artery (endothelium-dependent vasodilatation) in 136 subjects, with or without evidence of coronary artery disease. Endothelial dysfunction was diagnosed if flow-mediated dilatation was less than 4.5%. Of the 136 subjects (age group 40-70 years) recruited for the study, 94 were males and 42 females. Sixty-eight subjects had evidence of coronary artery disease as diagnosed by documented hospitalization due to myocardial infarction or acute coronary syndrome, proved by coronary angiography when feasible or noninvasive cardiac evaluation. Endothelial dysfunction was detected in 90 subjects (66.2%). Prevalence of coronary artery disease was higher among subjects with endothelial dysfunction compared to those without (57.5% v. 34.7%, p=0.013). Prevalence of endothelial dysfunction was significantly higher among subjects with coronary artery disease as compared to those without coronary artery disease (76.4% v. 55.8%, p=0.012). The present study showed a sensitivity of 76%, specificity of 44%, positive predictive value of 58% and negative predictive value of 65% for endothelial dysfunction in the prediction of coronary artery disease. Multiple regression analysis using coronary artery disease as a dependent variable revealed a statistically significant association with endothelial dysfunction (p=0.033) even after the inclusion of traditional risk factors into the model. CONCLUSIONS: We conclude that endothelial dysfunction shows a strong association with coronary artery disease and can be a useful noninvasive tool for the evaluation of coronary artery disease.     

Comparison of endothelial function evaluated by strain gauge plethysmography and brachial artery ultrasound

BACKGROUND: the cardiac Renin-Angiotensin system (RAS) plays an important role in the regulation of coronary flow and cardiac function and structure in normal and pathological conditions such as ischemia-reperfusion (I/R) injury. The aim of this study was to investigate the effects of the Angiotensin II type 1 (AT-1) receptor antagonist MK-954 (losartan potassium) on postischemic endothelial dysfunction and NOS mRNA expression (inducible nitric oxide synthase, iNOS; endothelial nitric oxide synthase, eNOS) in isolated working rat hearts. METHODS: isolated working rat hearts were subjected to 15 min global ischemia and 180 min reperfusion. MK-954 was added to perfusion buffer (a modified Krebs-Henseleit solution) at 1 microM concentration. We assessed functional parameters, creatin kinase (CK) release, heart weight changes, microvascular postischemic hyperpermeability (FITC-albumin extravasation) and morphological ultrastructural alterations. eNOS and iNOS mRNA levels were also detected by the means of multiplex RT-PCR technique using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) gene as internal control; results were expressed as densitometric ratio. RESULTS: in Losartan-treated hearts we observed a significant reduction of postischemic contractile dysfunction, CK release and myocardial ultrastructural damage; postischemic FITC-albumin extravasation was significantly reduced respect to controls. Moreover, 1 microM Losartan produced a significant reduction of eNOS/G3PDH respect to untreated hearts submitted to I/R. Regarding iNOS/G3PDH ratio, no significant changes were detected in Losartan-treated hearts compared with controls. CONCLUSIONS: our study revealed that Losartan treatment before ischemia, and during reperfusion, is able to reduce the reperfusion injury of the rat heart by reducing mechanical and microcirculatory dysfunction and necrotic cell death, ameliorating cardiac ultrastructure and endothelial protection, probably inducing eNOS over-expression and reducing post-ischemic hyperpermeability of coronary microcirculation.     

停用辛伐他汀对健康男性肱动脉内皮功能的影响

目的 观察停用辛伐他汀对Tc水平正常健康男性肱动脉内皮功能的影响.方法 16例健康青年男性服用20mg辛伐他汀4周后停药,分别检测停药前后不同时间点肱动脉内皮依赖性舒张功能(FMD),并测定血管活性物质--NO、血浆内皮素和6-酮-前列腺素F1α(6-keto-PGF1α)以及血脂参数的变化.结果 健康男性服用辛伐他汀4周后,在停药第1天观察到FMD较停药前明显降低,甚至低于未服药时的基线水平(P＜0.05).停药后血清NO水平较停药前和基础值亦明显降低,其变化与FMD的变化一致.停药后血浆内皮素水平升高,6-keto-PGF1α水平降低.血清LDL-C在停药后最初2d内无明显改变,其变化与FMD无明显相关.结论 健康男性服用辛伐他汀后突然停药,不仅使该药对肱动脉内皮功能的改善作用迅速消失,而且还对血管内皮功能造成进一步损害,该不良影响可能与循环中NO水平降低有关,是非TC依赖性的.     

Association of coronary risk factors and endothelium-dependent flow-mediated dilatation of the brachial artery.

Impaired endothelial function has been reported to be the initial step in atherosclerosis. Some coronary risk factors independently relate to impaired endothelial function. However, few studies have examined the association between coronary risk factors and endothelial function in patients who have multiple risk factors without clinical atherosclerosis. This study was undertaken to elucidate the relationship between accumulation of coronary risk factors and vascular endothelial dysfunction. We examined 101 subjects with one or more coronary risk factors 56.8 +/- 1.0 years old and 40 age-matched control subjects without coronary risk factors. We measured brachial artery diameter non-invasively using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia caused by endothelium-dependent vasodilatation, and after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. The percentage change in flow-mediated diameter (%FMD; deltaD/D x 100), in subjects with one or more coronary risk factors was significantly lower than that in control subjects(4.8 +/- 0.3% vs. 6.7 +/- 0.5%, p < 0.01). Endothelium-independent vasodilatation by nitroglycerin did not differ between the two groups. Endothelial function was impaired according to the accumulation of coronary risk factors. On multiple regression analysis, the number of risk factors, age, and brachial artery diameter at rest showed significant correlation with %FMD. Our results suggest that an accumulation of coronary risk factors was significantly related to impairment of endothelial function.