Peripheral vascular endothelial function in essential hyperhidrosis.

BACKGROUND: Essential hyperhidrosis, a disorder of the eccrine sweat glands, is associated with sympathetic overactivity and the aim of the present study was to determine endothelium-dependent vasodilator function in patients with this condition. METHODS AND RESULTS: Using high-resolution ultrasound, the diameter of the brachial artery at rest and during reactive hyperemia (flow-mediated dilatation, %FMD endothelial-dependent stimulus to vasodilatation), as well as after sublingual administration of nitroglycerin (%NTG endothelium-independent vasodilatation) was measured in 18 subjects (mean age 27+/-5 years) with essential hyperhidrosis and 24 healthy control subjects (mean age 29+/-5 years). Baseline brachial artery diameter and FMD were comparable in both groups (BAD: 4.1+/-0.7 mm vs 4.3+/-0.5 mm (control), p = 0.8; FMD: 5.6+/-1.9% vs 6.7+/-2.2%, p=0.1). The time-averaged flow velocity during peak reactive hyperemia was similar in the 2 groups (75+/-11 cm/s vs 72+/-10 cm/s, p = 0.5), nor did NTG-induced dilatation in the patients with essential hyperhidrosis differ significantly from that in healthy control subjects (12.8+/-2.7% vs 14.0+/-3.6%, p = 0.3). CONCLUSION: These findings suggest that endothelium-dependent dilatation of large conduit arteries is preserved in essential hyperhidrosis and it seems to be a localized disorder of the eccrine sweat glands rather than a generalized disorder involving vascular endothelium.     

Gender difference in age-related changes in vascular function

PURPOSE: We investigated whether, in a randomly selected population of 55-year-old men and women, there is a relationship between vascular function measured as flow-mediated (endothelium-dependent) and nitroglycerine-mediated (nonendothelium-dependent) dilatation of the brachial artery and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood-lipids and high blood pressure. The results are compared with those in a young healthy population of 35-year-olds. SUBJECTS: A total of 57 men (73% of the invited males) living in the community and 47 women (62% of the invited females) participated and were compared with a previously studied 35-year-old population (52 men and 56 women). METHODS: Basal brachial artery diameter was measured by high-frequency ultrasound methods. Endothelial function was measured as flow-mediated dilatation (FMD) in response to reactive hyperaemia. The nonendothelium-dependent vasodilatation was measured after administering sublingual nitroglycerine (NTG). RESULTS: Flow-mediated endothelium-dependent dilatation was similar in men and women being 3.1 +/- 2.5% (mean +/- SD) in men vs. 2.6 +/- 2.3% in women. FMD of the brachial artery was negatively correlated with vessel size in both men and women (P < 0.001). Men had larger brachial artery diameter than women (4.6 +/- 0.7 vs. 3.6 +/- 0.4 mm, P < 0.001). There was no difference in FMD or in NTG-induced dilatation in the women receiving oral oestrogen replacement therapy compared with those that did not. The women taking oral oestrogen had lower cholesterol than those not taking oral oestrogen (P=0.04). FMD was not correlated with any of the risk factors. NTG-induced vasodilatation was correlated with the body mass index (BMI) in men (P=0.01) and a combined risk factor score in women (P=0.04). There was a large increase in the number of subjects with cardiovascular risk factors in the 55-year-old men and women compared with the 35-year-olds. The distribution of risk factors was fairly equal amongst men and women. CONCLUSION: There are no correlations between any of the conventional cardiovascular risk factors and FMD in a population of 55-year-olds, but there is a high prevalence of risk factors in the 55-year-old age group. NTG-induced vasodilatation correlated with the BMI in men and a combined risk-factor score in women. FMD-induced vasodilatation is smaller in women at 55 years of age than at 35 years of age. FMD was similar in men at 35 and 55 years of age and in men and women at 55 years of age. The smaller FMD in women at 55 years of age, compared with at 35, could be due to postmenopausal hormonal changes.     

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.     

Reduction of peripheral flow reserve impairs endothelial function in conduit arteries of patients with essential hypertension

BACKGROUND: A diminished flow reserve in resistance vessels is a hallmark of hypertensive microvascular disease. Hypertension is associated with structural alterations in the microcirculation and a reduced endothelium-dependent dilation in conduit arteries. Both have been demonstrated to predict future cardiovascular events. OBJECTIVE: We hypothesized that a reduced peripheral flow reserve impairs endothelial function in upstream conduit arteries in patients with arterial hypertension. DESIGN: In 43 hypertensive patients (HT) and 38 normotensive controls (NT) endothelial function of the brachial artery was assessed by measurement of flow-mediated dilatation (FMD), using high-resolution ultrasound. Peripheral flow reserve (FR) was determined via measurements of forearm blood flow at rest and during increments of reactive hyperaemia, using venous occlusion plethysmography. RESULTS: FMD was markedly impaired in HT (3.6 +/- 0.3%) as compared with NT (10.2 +/- 0.3%), whereas maximum brachial artery diameter following endothelium-independent dilatation was similar in both groups. In hypertensive patients FR was significantly reduced (HT, 3.2 versus NT, 6.0) during reactive hyperaemia after 5 min of ischaemia. FR was associated with FMD (r = 0.68, P < 0.01). Multiple stepwise regression analysis identified FR as a strong independent variable determining the extent of FMD (r2 = 0.46, P < 0.01). In HT the dose-response curve of FMD upon stepwise increases of FR was shifted significantly to the right. Normalization of FR improved FMD in HT by more than 60%. CONCLUSIONS: In essential hypertension a reduced FR contributes to the endothelial dysfunction of upstream conduit arteries. These findings may have therapeutic and prognostic implications in patients with arterial hypertension.     

Handgrip exercise increases postocclusion hyperaemic brachial artery dilatation

OBJECTIVE: To examine the effect of handgrip exercise induced ischaemia on non-invasive assessment of endothelial function in the brachial artery. DESIGN AND SETTING: High frequency ultrasound was used to measure brachial artery diameter at rest and after reactive hyperaemia induced by forearm cuff occlusion with and without handgrip exercise induced ischaemia. SUBJECTS: 10 healthy subjects, < 40 years, without known cardiovascular risk factors. MAIN OUTCOME MEASURES: Brachial artery dilatation and blood flow. RESULTS: Hyperaemia following forearm occlusion with handgrip exercise induced ischaemia increased brachial artery diameter significantly more than hyperaemia following occlusion alone, 6.9 (3.2)% and 4.5 (1.6)%, respectively (95% confidence interval 0.3% to 4.5%). There was no difference in peak blood flow with and without exercise induced ischaemia CONCLUSIONS: Handgrip exercise induced ischaemia with forearm occlusion caused more pronounced brachial artery dilatation than occlusion alone without change in peak blood flow. This suggests continued brachial artery responsiveness to the stimulus of ischaemia despite maximum blood flow and peripheral vasodilatation with occlusion alone.     

Variability of flow mediated dilation: consequences for clinical application

BACKGROUND: Flow mediated vasodilatation (FMD), a non-invasive tool to assess endothelial function, has been shown to have prognostic value for the development of cardiovascular disease. Conventional B-mode ultrasonography has been criticised for its 'limited' resolution in vivo, which complicates reliable detection of the minute diameter changes during reactive hyperaemia. In the present study we evaluated the physical resolution, reproducibility and the capability to detect FMD impairment of a wall tracking system (WTS). METHODS: The resolution of WTS was compared with that of intravascular ultrasound (IVUS) in pig femoral arteries in vivo. Subsequently, intra- and interobserver variability of FMD testing with WTS was evaluated in 75 healthy volunteers. Finally, the effect of smoking as single risk factor for atherosclerosis on FMD in vivo was assessed. RESULTS: WTS and IVUS readings were not different (difference in arterial cross sectional area 1.97 mm(2), r=0.87). Intrasession coefficient of variation in baseline diameter was 1.1% (extremes 0.06--2.0%). Inter-session baseline diameter variation was 3.6 and 3.8% for each observer and 4.1% between observers. Intra-individual variability in FMD between sessions was considerable with coefficients of variation of 13.9% for FMD and 9.3% for NTG. Smokers had impaired FMD responses compared with matched non-smokers (4.7+/-2.4 vs. 9.6+/-4.4%, P<0.001), whereas NTG induced vasodilatation did not differ (13.4+/-6.2 vs. 15.4+/-5.1%; p=ns). CONCLUSION: WTS is a suitable technique for reproducibly assessing the brachial artery diameter in vivo with a accuracy comparable to that of IVUS. Using this sensitive technique the reproducibility of FMD in vivo proves to be poor mainly due to physiological factors. Whereas this seriously limits the use of FMD as follow-up parameter for individual subjects, FMD is demonstrated to be a useful research tool at group level.     

Reproducibility of different methods to measure the endothelial function

This study compares the reliability and reproducibility of flow-mediated dilatation (FMD) and peripheral arterial tonometry (PAT) to assess endothelial function. Eighteen volunteers with coronary heart disease underwent simultaneous testing of FMD by means of brachial artery ultrasound scanning and PAT with the EndoPAT 2000. The subjects underwent both tests twice with an interval of 30 minutes and the same protocol was repeated 2 days later. The within-day variability was lower for the FMD measurements than for the PAT measurements (10% versus 18%; p < 0.05). The between-day variability was similar (11%). A significant correlation was found between PAT and FMD (r = 0.57, p < 0.001). The typical errors of measurements for FMD were lower than those for PAT. In conclusion, in this study, FMD demonstrated the best reliability for the within- and between-day and separate day measurements when compared to PAT.     

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.     

Endothelium-dependent flow-mediated vasodilatation,insulin resistance and the metabolic syndrome in 60-year-old men

OBJECTIVES: To evaluate the endothelium-dependent flow-mediated vasodilatation (FMD) in the brachial artery and to study the relationship to insulin sensitivity and to the metabolic syndrome in 60-year-old clinically healthy men. SUBJECTS: The men were randomly selected from the general population (n = 55). The subjects with the metabolic syndrome were defined according to a definition proposed by a working group associated with the World Health Organization (WHO). METHODS: Ultrasound images for measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery, both with and without ischaemic hand exercise during the occlusion. Insulin-mediated glucose uptake was determined by euglycaemic hyperinsulinaemic clamp as a measure of insulin sensitivity. RESULTS: The FMD was in the total group 3.2% when hyperaemia was induced by occlusion only and 8.7% after occlusion plus ischaemic hand exercise (P < 0.001, n = 51). However, no relationship was observed between any measure of FMD and insulin-mediated glucose uptake (r = -0.05 and r = 0.06, n = 47, P > 0.30). Furthermore, subjects with the metabolic syndrome (n = 13) did not differ in any measure of FMD compared with those with no risk factors (n = 11). CONCLUSION: In this study the ultrasound method to evaluate endothelial function did not show that low insulin sensitivity or the metabolic syndrome were associated with impaired FMD in otherwise clinically healthy 60-year-old men.     

Antiplasmin correlates to arterial reactivity in a healthy population of 35-year-old men and women

OBJECTIVE: To study whether haemostasis function variables correlate with endothelial function and other vasomotion characteristics of the brachial artery in a randomly selected healthy population of 35-year-old men and women. DESIGN: Endothelial function was measured as flow mediated dilatation (FMD) of the brachial artery during reactive hyperaemia and the nonendothelial dependent dilatation after sublingual nitroglycerin (NTG) was administered. Haemostasis and fibrinolysis function were estimated by analysis of von Willebrand factor, plasminogen activator inhibitor-1, antiplasmin and fibrinogen. SETTING: A general medicine research centre and a university hospital. SUBJECTS: Randomly chosen men (n = 53) and women (n = 56). RESULTS: Univariate correlation analysis showed significant correlations between haemostasis factors, conventional risk factors for cardiovascular disease and indices of vasomotion of the brachial artery. In multivariate analysis, with haemostasis variables and conventional risk factors included, antiplasmin was the strongest explanatory variable for FMD. When antiplasmin was removed from the analysis, the r-value dropped from 0.46 to 0.35. Antiplasmin also correlated with NTG-induced dilatation (positively) and brachial diameter at rest (negatively), albeit less consistently. CONCLUSIONS: Antiplasmin correlates significantly and independently to FMD, reflecting endothelial function, and also to brachial artery diameter at rest and nitroglycerin-induced dilatation. In multivariate analysis these correlations of antiplasmin to arterial characteristics were stronger than for 'conventional' risk factors, such as smoking, blood pressure and serum cholesterol.     

Oral L-arginine improves endothelial function in healthy individuals older than 70 years

Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects (age 73.8 +/- 2.7 years) took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia. Baseline artery diameter was 3.88 +/- 0.18 mm. L-Arginine significantly improved FMD (to 5.7 +/- 1.2%, p < 0.0001), whereas placebo had no effect (-0.25 +/- 0.7%; n.s.). After L-arginine, plasma levels of L-arginine increased significantly (114.9 +/- 11.6 versus 57.4 +/- 5.0 micromol/l), but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals (3.9 +/- 0.2 versus 1.0 +/- 0.1 micromol/l; p < 0.0001). ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio (p < 0.05). We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio.     

Does a glass of red wine improve endothelial function?

AIMS: To examine the acute effect of red wine and de-alcoholized red wine on endothelial function. METHODS AND RESULTS: High frequency ultrasound was used to measure blood flow and percentage brachial artery dilatation after reactive hyperaemia induced by forearm cuff occlusion in 12 healthy subjects, less than 40 years of age, without known cardiovascular risk factors. The subjects drank 250 ml of red wine with or without alcohol over 10 min according to a randomized procedure. Brachial artery dilatation was measured again 30 and 60 min after the subjects had finished drinking. The subjects were studied a second time within a week of the first study in a cross-over design. After the red wine with alcohol the resting brachial artery diameter, resting blood flow, heart rate and plasma-ethanol increased significantly. After the de-alcoholized red wine these parameters were unchanged. Flow-mediated dilatation of the brachial artery was significantly higher (P<0.05) after drinking de-alcoholized red wine (5.6+/-3.2%) than after drinking red wine with alcohol (3.6+/-2.2%) and before drinking (3.9+/-2.5%). CONCLUSION: After ingestion of red wine with alcohol the brachial artery dilated and the blood flow increased. These changes were not observed following the de-alcoholized red wine and were thus attributable to ethanol. These haemodynamic changes may have concealed an effect on flow-mediated brachial artery dilatation which did not increase after drinking red wine with alcohol. Flow-mediated dilatation of the brachial artery increased significantly after de-alcoholized red wine and this finding may support the hypothesis that antioxidant qualities of red wine, rather than ethanol in itself, may protect against cardiovascular disease.     

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.     

Serum uric acid is associated with microvascular function in hypertensive individuals

We investigated the relationship of serum uric acid (UA) with resting forearm blood flow (FBF), reactive hyperaemia (RH) and flow-mediated dilation (FMD) of the brachial artery in hypertensive adults (n=506, mean age 62 years, 59% women). UA was measured by a colorimetric method. FBF, RH and FMD were measured by brachial artery ultrasound. Regression analyses were used to assess whether UA was associated with FBF, RH and FMD before and after adjustment for age, sex, systolic BP, diabetes, total and high-density lipoprotein cholesterol, smoking, body mass index (BMI), C-reactive protein (CRP), serum creatinine, alcohol intake, statin and diuretic use and brachial artery diameter (BAD). UA was significantly associated with FBF (P<0.0001) and RH (P=0.0001) but not with FMD (P=0.43). After adjustment for the covariates listed above, higher UA level remained independently associated with a higher FBF (P=0.012) and lower RH (P=0.004). The independent predictors were as follows: (a) higher FBF: lower age, higher BMI, history of smoking, statin use, higher CRP, higher BAD and higher UA levels; (b) lower RH: higher BMI, diabetes and higher UA levels; (c) lower FMD: greater age, male sex, higher BMI, history of smoking, statin use and higher BAD. We conclude that in hypertensive individuals, higher UA levels are associated with higher resting FBF and lower RH, markers of microvascular function, but not with brachial artery FMD.     

Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol and its oxidative modification have been described to be involved in the process of atherogenesis. Bilirubin, an antioxidant, prevents oxidative modification of LDL and therefore may protect from atherosclerosis and coronary heart disease (CHD). Impaired brachial artery flow-mediated dilatation (FMD), which means endothelial dysfunction (ED) and carotid intima-media thickness (IMT) are predictors for the development and progression of atherosclerosis. In the present study, FMD and IMT were studied in healthy subjects with lower and higher serum bilirubin concentrations in physiological ranges. METHODS: Ninety-one healthy subjects between 25 and 45 years of age (47 with lower and 44 with higher serum bilirubin concentrations) were included in this study. Carotid IMT and brachial artery flow-mediated dilatation was measured by means of high-resolution vascular ultrasound. FMD was assessed by establishing reactive hyperemia and endothelium-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. RESULTS: EDD in subjects with lower serum bilirubin concentrations was significantly worse than in those with higher serum bilirubin concentrations (11.6+/-4.4% versus 7.2+/-4.7%, respectively, p<0.0001). EID measurements were not significantly different between the groups (16+/-5.1% versus 16.8+/-7%, respectively). In addition, carotid IMT was significantly greater in subjects with lower serum bilirubin concentrations (0.5+/-0.13 mm versus 0.42+/-0.07 mm, p<0.0001). Furthermore, FMD in women with lower serum bilirubin concentrations was significantly lower than in women with higher serum bilirubin concentrations (11.5+/-4.9% and 17.5+/-4.7%, respectively, p<0.001). Accordingly, men with lower serum bilirubin concentrations had significantly lower FMD as compared to hyperbilirubinemic ones (11.7+/-3.6% versus 16.7+/-4.8%, respectively, p=0.009). Conversely, carotid IMT was significantly greater in both women and men with lower serum bilirubin concentrations compared to the subjects with elevated serum bilirubin concentrations (0.51+/-0.08 versus 0.41+/-0.08, p<0.001; 0.55+/-0.12 versus 0.40+/-0.07, p=0.002, in women and men, respectively). CONCLUSION: The healthy subjects with lower serum bilirubin concentrations show significant ED and increased carotid IMT, which are predictors for atherosclerosis.     

Blood lipids and endothelial function in glycogen storage disease type III

We have assessed early indicators of arterial disease in patients with glycogen storage disease type III (GSD III; McKusick 232400), investigating the plasma lipid and lipoprotein profile and endothelial function. Eleven patients, aged 10–39 years, were recruited together with age-, sex- and smoking status-matched controls. Brachial artery responses were assessed by high-resolution ultrasonographic measurement of the diameter of the brachial artery at baseline, after reactive hyperaemia and in response to sublingual glyceryl trinitrate (GTN).The means of plasma cholesterol (total and HDL and LDL subfractions), triglycerides, apo-A1, apo-B, Lp(a) and the atherogenic index were similar in both groups. Cardiac troponin I was below the lower limits of detection (<0.03g/L) in all subjects. The GSD III patients had similar body mass index (BMI) and brachial artery diameter to the control group (BMI 22.6±5.6 vs 22.3±5kg/m²; brachial artery diameter 3.4±0.5 vs 3±0.7mm). When compared to the baseline diameter, the maximal flow-mediated dilatation of the brachial artery after reactive hyperaemia was 9.3±2.1% (mean±SD) in the GSD III patients and 6.5±3.5% in the control group, a difference of 1.8% (95% CI 0.07% to 5.5%). The maximal dilatation of the brachial artery after GTN administration was 18.3±6.4% in the GSD III patients and 17.9±6.5% in the control group, a difference of 0.4% (95% CI –6.9% to 7.7%.In conclusion, we found no evidence of abnormal plasma lipid and lipoprotein profile or endothelial dysfunction in patients with GSD III. They are unlikely to be at increased risk of premature atherosclerosis.     

Vascular abnormalities in primary amyloidosis.

AIMS: Primary amyloidosis (AL) is a systemic disease; however, there is limited information regarding the presence and character of vascular abnormalities. METHODS AND RESULTS: Validated ultrasound techniques were used to prospectively determine carotid artery intimal-medial thickness (IMT) and brachial artery flow-mediated dilatation (FMD) in 59 consecutive AL patients and 17 age-similar, healthy, asymptomatic volunteers (CON). Carotid IMT was increased in AL when compared with CON (0.07 +/- 0.02 vs. 0.04 +/- 0.01 mm, P < 0.01). Similarly, brachial artery FMD was significantly lower in AL when compared with CON subjects (3 +/- 7 vs. 12 +/- 8%, P < 0.01). Multivariable analysis revealed that AL was associated with larger IMT and lower FMD after controlling for several confounding variables. However, within AL cases, there was not a significant association of cardiac vs. non-cardiac involvement with IMT or FMD (P = 0.1 and 0.2, respectively). CONCLUSION: AL is associated with abnormal vascular morphology and endothelial dysfunction. Vascular abnormalities do not appear to be related to echocardiographic evidence of cardiac involvement.     

Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli.

OBJECTIVE: To examine the relation between endothelial dependent and endothelial independent stimuli of varying intensity and measures of vascular function in the brachial artery of young healthy adults, to determine whether these responses are consistent and can be used to assess endothelial function. DESIGN AND SETTING: High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia induced by forearm cuff occlusion, and after sublingual isosorbide dinitrate (ISDN). Each subject was assigned to a random order of six cuff occlusion times (30 seconds, 1.5, 2.5, 3.5, 4.5, and 8 minutes) and six doses of ISDN (10, 20, 50, 100, 200, and 400 micrograms). SUBJECTS: Three males and three females mean age 31 years (range 25 to 43) with no known risk factors for cardiovascular disease. MAIN OUTCOME MEASURES: Flow mediated, endothelial dependent dilatation was compared to duration of cuff occlusion, peak reactive hyperaemia, and duration of increased flow. Nitrate induced, endothelial independent dilatation was compared to dose of ISDN and change in flow. RESULTS: Vessel dilatation and duration of peak flow change increased with longer duration of cuff occlusion. After 4.5 minutes of occlusion, flow mediated dilatation was mean (SD) 96 (6)% of maximal response and did not increase significantly with longer occlusion times. No significant dilatation occurred after 10 or 20 micrograms of ISDN in any subject. With increasing doses up to 200 micrograms there was an increase in dilatation. Endothelial independent dilatation did not increase significantly with doses of ISDN above 200 micrograms. CONCLUSIONS: Measures of arterial function vary with duration of blood flow occlusion and ISDN dose. Maximum arterial response was reached in all subjects after 4.5 minutes of blood flow occlusion or 200 micrograms of ISDN. Therefore, these variables produce consistent reproducible measures of endothelial function.     

New monitoring software for larger clinical application of brachial artery flow-mediated vasodilatation measurements

BACKGROUND: The reproducibility of brachial artery flow-mediated vasodilatation (FMD) is limited by the operator dependence of most measurement methods. METHODS: A new automated computerized analysis of brachial artery ultrasound scan providing a continuous evolution of the diameter during acute hyperemia, reactive to short hyperemia of the forearm and hand, was tested in 10 normal volunteers and 26 asymptomatic patients with cardiovascular risk factors such as hypertension, hypercholesterolemia, heavy smoking, history of premature coronary heart disease and the metabolic syndrome. FMD was the percentage of the maximum hyperemic diastolic diameter from baseline. Within-reading variations in FMD and diameters were assessed by reading one scan from the same subject twice by two observers. The within-subject variability of FMD was assessed by analysing two repeated measurements in the same subject by the same operator 1 h, 1 week or 1 month apart. RESULTS: Coefficients of variation (CV) of repeated FMD readings were 7.5% in normal volunteers and 6.9% in patients with risk factors. CV of repeated FMD measurements 1 h apart were 7.8% in normal volunteers and 16.5% in patients with risk factors. In normal volunteers, CV of repeated FMD measurements 1 week apart was 9.6%, and in patients with risk factors CV of repeated FMD measurement 1 month apart was 18.1%. CONCLUSION: This method overcomes the variability of FMD measurement seen with conventional manual analysis in normal volunteers, and to a lesser extent in patients with major cardiovascular risk factors, thus supporting its clinical applicability to patients with disease conditions.     

Correlation of endothelial function in large and small arteries in human essential hypertension

OBJECTIVES: The structure and function of blood vessels varies along the vascular tree, and alterations found in hypertension are also different. The aim of this study was to determine whether non-invasive measurement of endothelial function in conduit arteries reflects that of subcutaneous resistance arteries measured in vitro. METHODS AND RESULTS: Sixteen essential hypertensive patients (aged 50 +/- 2 years) were studied. Flow-mediated dilation (FMD) during reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (NTG)-induced dilatation (endothelium-independent) were assessed in brachial arteries by ultrasound. Structure, and acetylcholine (10(-9) to 10(-4) mol/l) and sodium nitroprusside (SNP, 10(-8) to 10(-3) mol/l)-induced vasorelaxation of resistance arteries dissected from gluteal subcutaneous biopsies were measured in vitro using a pressurized myograph. Brachial artery FMD and NTG-induced dilatation were 8.4 +/- 1.0 and 18.1 +/- 1.4%, respectively. Resistance arteries of hypertensive patients showed greater media:lumen ratio (8.6 +/- 0.4 versus 5.9 +/- 0.3% in normotensive subjects, P< 0.01), and maximal acetylcholine responses was diminished to 75 +/- 6% compared to normotensive subjects (97 +/- 2%, P< 0.01). FMD correlated with maximal acetylcholine responses (r2 = 0.57, P< 0.001). FMD did not correlate significantly with the media: lumen ratio of resistance arteries (r2 = -0.22, P= 0.07). By multivariate analysis, FMD predicted resistance artery endothelial function independently of age, sex, body mass index, blood lipid status and lumen diameter of brachial artery (beta = 0.81, P< 0.001). CONCLUSIONS: Endothelial dilatory responses are similar in large and small arteries in hypertensive patients. Abnormal FMD in the brachial artery predicts the presence of endothelial dysfunction in human resistance arteries, suggesting that impairment of endothelial function is a generalized alteration in hypertension. Ultrasound measurement of endothelial dysfunction in the brachial artery appears to be less sensitive than in-vitro measurement in resistance arteries.