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.     

Measurement of flow-mediated dilatation of the brachial artery is affected by local elastic vessel wall properties in high-risk patients

OBJECTIVES: To assess whether the validity of endothelial function measurement by flow-mediated dilatation (FMD) is affected by local brachial artery stiffness (distensibility coefficient; DC) and arterial wall thickness (intima-media thickness, IMT). BACKGROUND: FMD measurement relies on assessment of arterial diameter change. Increased IMT and decreased DC might physically limit dilatation of the brachial artery in spite of healthy endothelium. METHODS: DC, IMT and FMD of the brachial artery were simultaneously measured in 349 patients with advanced atherosclerosis or cardiovascular risk factors. The relations between FMD and age, and FMD and current smoking were regarded as a proxy for the relation between FMD and true endothelial function. RESULTS: The relations between FMD and age, and FMD and smoking, were significantly modified by brachial artery DC. No modification was found for IMT. The interaction terms were statistically significant (p=0.03 and 0.04, respectively). The relation between FMD and age, and FMD and smoking was progressively more pronounced in patients with more elastic arteries. CONCLUSION: The results of our study indicate that increased arterial stiffness may interfere with valid measurement of FMD and that patients with stiff arteries may be considered for exclusion from analyses involving FMD to ensure its validity.     

Endothelial function and peripheral vasomotion in the brachial artery in neurally mediated syncope

BACKGROUND: Paradoxical peripheral vasodilation is one of the suspected mechanisms of neurally mediated syncope. Parasympathetic stimulation following sympathetic activation during orthostatic stress mainly contributes to this vasodilation. HYPOTHESIS: Since endothelial function modulates peripheral vascular tone, this study aimed to determine whether endothelial function and inappropriate peripheral vasomotion has a significant role in the pathogenesis of neurally mediated syncope. METHODS: To investigate whether endothelial function is augmented or whether abnormal peripheral vasomotion exits, flow-mediated dilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl trinitrate-induced dilation (0.3 mg, GTN-D, endothelium-independent vasodilation) were measured in the brachial artery in 16 patients with neurally mediated syncope, aged 33 +/- 10 years, by using high-resolution ultrasound. All patients underwent positive head-up tilt testing. These measures were compared with those in 16 control subjects matched with the patients by age, gender, and coronary risk factors. For FMD, percent diameter changes were obtained from baseline to hyperemic conditions (1 min after 5 min occlusion of the forearm artery). There were five smokers in both the patient and the control groups, but there was no structural heart disease in either group. RESULTS: Baseline brachial artery diameters were comparable (3.8 +/- 0.6 vs. 3.8 +/- 0.7 mm, NS). Flow-mediated dilation in patients with neurally mediated syncope had a normal value of 9.8 +/- 5.0% despite the inclusion of five smokers. Flow-mediated dilation and GTN-D in patients with neurally mediated syncope were significantly greater than those in controls (9.0 +/- 5.0 vs. 3.0 +/- 3.5%, p<0.05; 18.4 +/- 5.5 vs. 14.1 +/- 4.4%, p<0.05). CONCLUSIONS: Augmented endothelial function and/or abnormal peripheral vasomotion in peripheral arteries are important in patients with neurally mediated syncope in selected populations.     

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.     

Endothelial function of the popliteal artery in patients with coronary artery disease

Coronary artery disease (CAD) is associated more closely with atherosclerosis in the popliteal than in the brachial artery. This case-control study aimed at clarifying whether endothelial dysfunction of patients with CAD can be detected non-invasively in the popliteal artery by means of ischemia-induced flow-mediated dilation (FMD) and cold pressor reaction (CPR), and how it compares with the brachial artery. We further investigated a new mode of evaluation of the CPR. Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal and brachial arterial diameter was monitored by ultrasound for 20 min following ischemia and cold pressor. For CPR, the difference between maximum and minimum diameter was defined as maximum vasomotion. In the popliteal artery, maximum vasomotion and FMD were significantly smaller in cases than in controls, the difference being more pronounced than in the brachial artery, where only maximum vasomotion was significantly smaller. After exclusion of current smokers, only the difference in maximum vasomotion of both arteries remained significant. We conclude that maximum vasomotion may be more sensitive for detection of endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is more pronounced in the popliteal artery than in the brachial artery.     

Is the Association Between Flow-Mediated Dilation and Cardiovascular Risk Limited to Low-Risk Populations?

OBJECTIVES: The aim of this research was to study whether the relation between endothelial function measured by flow-mediated dilation (FMD) of the brachial artery and cardiovascular risk factors is affected by the baseline cardiovascular risk. BACKGROUND: Flow-mediated dilation of the brachial artery is widely used as a measure of endothelial function. Relations between FMD and most cardiovascular risk factors have been described. METHODS: We performed a meta-regression analysis of 211 selected articles (399 populations) reporting on FMD and cardiovascular risk factors. Mean values of FMD; age; proportion of men; proportion of smokers; blood pressure; lipids; glucose; and the presence of diabetes mellitus, of hyperlipidemia, and of hypertension were retrieved from the articles. The 10-year risk of coronary heart disease (CHD) for each population was estimated based on the Framingham risk score. The relation between FMD and cardiovascular risk factors was assessed within each risk category by linear regression analysis, adjusting for age and gender, and weighted for the study size. RESULTS: A relation between FMD and cardiovascular risk factors was most clear in the category with lowest baseline risk (below 2.8% per decade). In populations with low baseline risk, for each % increase in Framingham risk, FMD decreased by 1.42% (95% confidence interval: 0.65 to 2.19). In medium- and high-risk populations, FMD was not related to risk (-0.02% [-0.27 to 0.22] and 0.06% [-0.02 to 0.13], respectively). These findings were independent of differences in brachial lumen diameter and technical aspects of the FMD measurement. CONCLUSIONS: Only in populations at low risk, endothelial function measured by FMD is related to the principal cardiovascular risk factors, and to the estimated 10-year risk of CHD.     

Vascular function correlates with risk factors for cardiovascular disease in a healthy population of 35-year-old subjects

OBJECTIVE: To investigate whether, in a healthy, randomly selected population of 35-year-old men and women, there is a relation between vascular function and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood-lipids, high blood pressure and heredity for cardiovascular disease, and to blood glucose. DESIGN: Basal brachial artery diameter was measured. Endothelial function was measured as flow mediated dilation (FMD) in response to reactive hyperaemia. The nonendothelial dependent dilation was measured after sublingual nitro-glycerine (NTG). SETTING: A research centre of general medicine and a university hospital. SUBJECTS: One hundred men and 100 women all 35 years old, were invited by letter. Sixty-six of the 92 men (72%) living in the community and 74 of the 88 women (84%) participated. RESULTS: Gender had the largest influence on FMD and NTG induced arterial dilation, probably reflecting the larger vessel diameters in the men as FMD and NTG induced dilation is inversely related to basal vessel size (r = -0.55, P < 0.001 and r = -0.40, P < 0.001). In women basal vessel diameter was positively correlated to blood glucose (r = 0.35, P = 0.009) and BMI (r = 0.34, P = 0.012) and negatively correlated to HDL cholesterol (r = -0.43, P = 0.001). FMD and NTG induced arterial dilation correlated with a combined risk factor score (r = -0.32, P = 0.019 and r = -0.31, P = 0.024). The men with the highest risk factor scores had larger vessel size and higher blood flow at rest compared to men without risk factors (4.8 +/- 0.6 mm, 240 +/- 84 mL min-1 and 4.0 +/- 0.8 mm, 139 +/- 72 mL min-1, respectively, P = 0.014 and P = 0.016). FMD or NTG induced dilation did not correlate to any of the risk factors in men. CONCLUSIONS: There are correlations between vascular reactivity and risk factors for IHD in women and correlations between vessel diameter and risk factors for IHD in both men and women already in a healthy population 35-year-old subjects. Further studies are needed to determine if the vessel diameter in itself, in a healthy population, is a sign of attenuated endothelial function.     

Effect of alcohol consumption on endothelial function in men with coronary artery disease

An inverse relationship between moderate alcohol consumption and coronary artery disease (CAD) has been observed in several epidemiologic studies. Whether improvement of endothelial function is involved in this beneficial effect is unknown. We investigated endothelial function of the brachial artery in 108 men with CAD, 54 of whom consumed alcohol on at least 1 day per week. Brachial artery diameter responses to hyperemic flow (FMD) and to administration of nitroglycerin (NTG) spray were measured using high- resolution ultrasonography. Coronary risk factors and hyperuricemia were present more frequently among drinkers, who also had higher concentrations of triglyceride and apolipoproteins C2, C3, and E. FMD was greater in drinkers (P<0.0001), while NTG-induced dilation was not. Multiple regression analysis showed alcohol consumption to be one of the factors favorably influencing FMD. These findings suggest that alcohol consumption may improve endothelial function in men with CAD.     

Association of cardiovascular risk factors with microvascular and conduit artery function in hypertensive subjects

BACKGROUND: Alterations in microvascular and conduit artery function contribute to target organ damage in hypertension. We investigated the association of cardiovascular (CV) risk factors with microvascular and conduit artery function in hypertensive subjects. METHODS: Participants included 504 hypertensives (aged 62.1 +/- 9.8 years, 42% men) from the community, without history of symptomatic CV disease. Brachial artery ultrasound was performed to measure forearm blood flow (FBF) at rest and during reactive hyperemia (markers of microvascular function) and flow-mediated dilatation (FMD) of the brachial artery (a marker of conduit artery endothelial function). The association of conventional and novel (homocysteine, C-reactive protein, fibrinogen, and lipoprotein a CV risk factors with microvascular function and FMD was tested in multivariable regression models. RESULTS: Variables independently associated with higher resting FBF were male sex, higher body mass index (BMI), smoking, and lower HDL-cholesterol; variables associated with lower hyperemic FBF included greater age, female sex, and diabetes. Higher plasma homocysteine was associated with lower hyperemic FBF in obese subjects (P for log homocysteine x BMI interaction = .0008). Variables independently associated with lower FMD were greater age, sex gender, history of smoking, and not using statins. Higher homocysteine was associated with lower FMD in subjects with higher systolic blood pressure (P for interaction = .0004). Hyperemic flow velocity was independently associated with FMD (P = .0006), but its inclusion as a covariate did not influence the association of CV risk factors with FMD. CONCLUSIONS: In asymptomatic subjects with essential hypertension, select CV risk factors were associated with microvascular and conduit artery function. Furthermore, the association of CV risk factors with conduit artery function appeared to be independent of downstream microvascular function.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.     

Relationship between endothelial function in the coronary and brachial arteries

BACKGROUND: Endothelial dysfunction is the first step in the progression to atherosclerosis, but little is known regarding whether there is a correlation in endothelial function between the coronary and peripheral arteries. HYPOTHESIS: We investigated the relationship between coronary and peripheral endothelial function. METHODS: In 41 patients (mean age 63 years; 23 men, 18 women) with angiographically normal coronary arteries, changes in brachial artery diameter in response to hyperemic flow and sublingual nitroglycerin (NTG) were measured by high-resolution ultrasonography. During coronary angiography, acetylcholine (ACh, 3 and 30 microg/min) and NTG were infused into the left coronary ostium. The diameter of the coronary artery was quantitatively measured and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to each drug infusion were expressed as the percent change from the baseline values. RESULTS: Flow-mediated dilation (FMD) of the brachial artery was 5.0 +/- 3.5% and correlated positively not only with the change in coronary diameter (ACh at 30 microg/min, r = 0.31, p < 0.05) but also with the change in CBF (ACh at 3 microg/min, r = 0.39, p < 0.05; ACh at 30 microg/min, r = 0.46, p < 0.01). Multivariate analysis demonstrated that FMD was one of the factors associated with the changes in coronary diameter and CBF. CONCLUSIONS: These results suggest that brachial endothelial function is associated with coronary endothelial function in patients with angiographically normal coronary arteries, suggesting that impairment of endothelial function may occur simultaneously in both coronary and peripheral arteries.     

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.     

The acute effect of green tea consumption on endothelial function in healthy individuals.

BACKGROUND: Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet. DESIGN AND METHODS: We studied 14 healthy individuals (age 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FMD of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (Il-6) and 1b (Il-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention. RESULTS: Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P<0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, Il-6, Il-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress. CONCLUSION: Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.     

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.     

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.     

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.     

Vascular Endothelial Function and Self-reported Sleep

BackgroundThe authors investigated the relationship between self-reported sleep characteristics and brachial artery flow-mediated dilation (FMD) in a community-based population. Previous studies document that sleep apnea may be related to endothelial dysfunction but disagree whether subjective reports of sleep may also reflect such associations.MethodsIn 684 subjects (32% male) aged between 37 and 60 years enrolled in the Emory-Georgia Tech Predictive Health Institute study, the authors measured reported sleep characteristics using the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index (PSQI) along with cardiovascular risk factors. Endothelial function was assessed using brachial artery FMD. Multivariate analysis of covariance was used to adjust for various cardiovascular risk factors including age, race, gender, smoking, hypertension, diabetes and body mass index.ResultsLower brachial artery FMD values were correlated with higher Epworth Sleepiness Scale scores (P = 0.0275), even after adjustment for risk factors (P = 0.03). Total PSQI score was unrelated to brachial artery FMD. However, lower sleep quality (PSQI component 1) was associated with lower brachial artery FMD (multivariate P = 0.038), and participants who coughed or snored during sleep also had lower brachial artery FMD (6.24% ± 3.42%) compared with those who did not (6.92% ± 4.30%) (P = 0.056). This difference remained significant after adjustment for risk factors (P = 0.03).ConclusionsIn a community-based population, our analysis indicates a significant association between sleepiness and snoring assessed by questionnaires and endothelial function. Simple subjective reports about individuals’ sleep may be highly revealing indicators of endothelial function impairment and thus important indicators of cardiovascular disease risk.     

Significant correlation between uric acid levels and flow-mediated dilatation in patients with masked hypertension

Background: Serum uric acid (UA) level is associated with prognosis in cardiovascular disorders such as sustained hypertension, diabetes mellitus and chronic kidney diseases. Increased UA levels in sustained hypertension may reflect early renal vascular alterations. However, it remains unclear if serum UA is associated with endothelial dysfunction in masked hypertensive patients. Methods: A total of 100 individuals (57% men and 43% women; mean 45?±?8 years) with masked hypertension were included in the present study. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. Results: Univariate regression analysis showed that the FMD was significantly negative correlated with uric acid (r?=??0.300, p?=?0.002), ambulatory 24-h systolic blood pressure (SBP) (r?=??0.275, p?=?0.008), hs-CRP (r?=??0.222, p?=?0.033) and diastolic aortic diameter (r?=??0.243, p?=?0.019). In multivariate linear regression analysis, only uric acid levels and ambulatory 24-h SBP were significantly associated with FMD. Conclusion: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.     

Effects of alcohol intake on endothelial function in men: a randomized controlled trial

BACKGROUND: Regular light consumption of alcohol appears to reduce the risk of cardiovascular disease, whereas in heavier drinkers the opposite effect is seen. This biphasic relationship could partly be due to contrasting actions of low and high alcohol intake on endothelial function. OBJECTIVE: To determine whether reducing alcohol intake in moderate-to-heavy drinkers (40-110 g/day) would improve conduit artery endothelial function as assessed by post-ischaemic brachial artery flow-mediated dilatation (FMD). METHODS: In a two-way cross-over study, 16 healthy men either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake during sequential 4-week periods. At the end of each period of FMD and glyceryl trinitrate-induced brachial artery dilatation, blood pressure, plasma lipids, homocysteine and biomarkers of alcohol consumption (gamma-glutamyl transpeptidase) and endothelial function (E-selectin, von Willebrand factor, endothelin-1) were assessed. RESULTS: The participants reduced their alcohol intake from 72.4 to 7.9 g/day. This self-reported reduction in alcohol intake was corroborated by significant decreases in gamma-glutamyl transpeptidase (24%). The decrease in alcohol intake resulted in reductions in total cholesterol (5%), high-density lipoprotein cholesterol (17%), homocysteine (9%) and systolic and diastolic blood pressure [5 mmHg (P = 0.01) and 4 mmHg (P = 0.003), respectively]. There was no effect of alcohol on FMD (6.23 +/- 0.75% compared with 6.24 +/- 0.71%, P = NS), glyceryl trinitrate-induced vasodilatation, E-selectin, endothelin-1 and von Willebrand factor. CONCLUSION: Substantial reduction in alcohol intake in healthy moderate-to-heavy drinkers does not improve endothelial function as measured by post-ischaemic flow-mediated dilatation of the brachial artery or biomarkers of endothelial function.     

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.