Normal Flow-mediated Dilation Research Articles

Endothelial dysfunction influences augmented aortic hemodynamic responses to metaboreflex activation in postmenopausal women.

Postmenopausal women experience augmented aortic hemodynamic responses to isometric handgrip (IHG) exercise and metaboreflex activation post-exercise muscle ischemia (PEMI). Relationships between endothelial function brachial artery flow-mediated dilation (FMD) and aortic stiffness carotid-femoral pulse wave velocity (cfPWV) with aortic pulsatile hemodynamics during IHG and PEMI have not been determined. The relationships between aortic hemodynamic responses to PEMI were evaluated. Aortic blood pressure (BP), wave reflection, and pressure of forward (Pf) and backward (Pb) waves were measured using arterial tonometry at rest, IHG at 30% maximal force, and PEMI in 30 (15/group) postmenopausal women with low (≤ 4.5%) and normal (≥ 5.5%) FMD. Hemodynamic responses were analyzed as the change (Δ) from rest to the last minute of IHG and PEMI. Brachial and aortic systolic BP (SBP) responses to IHG were higher in the low vs normal FMD group (P < 0.05). Aortic SBP (Δ20 ± 8 vs Δ11 ± 7mmHg), pulse pressure (PP) (Δ12 ± 8 vs Δ6 ± 4mmHg), augmented pressure (AP) (Δ5 ± 3 vs Δ2 ± 2mmHg), and Pb (Δ6 ± 4 vs Δ3 ± 2mmHg) responses to PEMI were greater (P < 0.05) in women with low vs. normal FMD. FMD was negatively correlated with aortic SBP, PP, AP, and Pb (P < 0.05) responses to PEMI. cfPWV was not correlated with responses to PEMI. Endothelial dysfunction relates to augmented aortic pulsatile load during metaboreflex activation, which may increase cardiovascular risk in postmenopausal women.

Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk.

Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30−55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1: <5%—n = 53) or a normal FMD response (group 2: 7−10%—n = 47). Results: Individuals exhibiting reduced FMD responses showed a reduced baseline-corrected microvascular arterial dilation response to flickering light (p = 0.039). In addition, they also exhibited a reduced arteriolar maximum dilation (p = 0.034), as well as a longer dilation reaction time (p = 0.048) and a lower dilation amplitude (p = 0.042) when compared to those with normal FMD values. Conclusion: In otherwise healthy middle-aged individuals, early signs of vascular dysfunction are reflected simultaneously at both macro- and microvascular levels.

Influence of endothelial function and arterial stiffness on the behavior of cervicocephalic arterial dissections: An observational study.

BackgroundThe mechanical and physiological properties of the arterial wall might affect the behavior of spontaneous cervicocephalic arterial dissections (CCAD). We aimed to determine the effects of endothelial function and arterial stiffness on the clinical characteristics and outcomes of CCAD using brachial flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (PWV).MethodsFrom a single-center database, we identified patients admitted from April 2011 to December 2021 with a diagnosis of CCAD who underwent both FMD and PWV. FMD was classified as normal and decreased according to institutional thresholds. PWV was categorized into tertiles. Comparative and multivariable analyses were performed to determine the effects of FMD and PWV values on major clinical outcomes.ResultsA total of 146 patients (age: 47 ± 11 years; men: 77.4%) were included. The main presentation was ischemic stroke in 76.7% of the patients, while 23.3% presented with headache or other symptoms. Healing of the dissection was observed in 55.8%. In multivariable analysis, Normal FMD levels (vs. decreased; adjusted OR: 4.52, 95% CI [1.95 −10.52]) were associated with spontaneous healing of the dissection. Highest PWV tertile (vs. lowest; adjusted OR: 17.05, 95% CI [3.07–94.82]) was associated with ischemic presentation. There was a higher ischemic stroke recurrence in the 3rd PWV tertile, and more frequent aneurysmal enlargement in the lowest PWV tertile, but their frequency was low, precluding multivariable analysis.ConclusionIn spontaneous CCAD, preserved endothelial function was associated with spontaneous arterial healing. Arterial stiffness is associated with ischemic presentation.

Impaired vascular endothelial function as a perioperative risk predictor \u2013 a prospective observational trial

BackgroundIn the recent years, an increasing number of patients with multiple comorbidities (e.g. coronary artery disease, diabetes, hypertension) presents to the operating room. The clinical risk factors are accompanied by underlying vascular-endothelial dysfunction, which impairs microcirculation and may predispose to end-organ dysfunction and impaired postoperative outcome. Whether preoperative endothelial dysfunction identifies patients at risk of postoperative complications remains unclear. In this prospective observational study, we tested the hypothesis that impaired flow-mediated dilation (FMD), a non-invasive surrogate marker of endothelial function, correlates with Days at Home within 30 days after surgery (DAH30). DAH30 is a patient-centric metric that captures postoperative complications and importantly also hospital re-admissions.MethodsSeventy-one patients scheduled for major abdominal surgery were enrolled. FMD was performed pre-operatively prior to major abdominal surgery and patients were dichotomised at a threshold value of 10%. FMD was then correlated with DAH30 (primary endpoint) and postoperative complications (secondary endpoints).ResultsDAH30 did not differ between patients with reduced FMD and normal FMD (14 (4) (median (IQR)) vs. 15 (8), P = 0.8). Similary, no differences between both groups were found for CCI (normal FMD: 21 (30) (median (IQR)), reduced FMD: 26 (38), P = 0.4) or frequency of major complications (normal FMD: 7 (19%) (n (%)), reduced FMD: 12 (35%), P = 0.12). The regression analyses revealed that FMD in combination with ASA status and surgery duration had no additional significant predictive effect for DAH30, CCI or Clavien-Dindo score.ConclusionFMD does not add predictive value with regards to DAH30, CCI or Clavien-Dindo score within our study cohort of patients undergoing abdominal surgery.Trial registrationThe study was registered in the German Clinical Trials Register (DRKS00005472), prospectively registered on 25/11/2013.

ENDOTHELIAL DYSFUNCTION AS A RISK FACTOR OF ARTERIAL HYPERTENSION PROGRESSION

Endothelial condition is one of the main factors determining the function of the healthy vessels and its change in arterial hypertension (AH). The aim of this study is to evaluate the role of endothelial dysfunction in prognosis of AH. Material and Methods. 918 young adults aged 20–29 years old and normal level of blood pressure (BP) were enrolled in a prospective observational study. The endothelial function was assessed using a brachial reactive hyperemia test with calculation of peak systolic (Vps), maximal terminal diastolic (Ved), time average maximal (TAMX), time average (TAV) blood flow velocity, spectral broadening index (SBI), resistance index (RI), pulsation index (PI), systole-diastolic ratio (SD), intima–media thickness and brachial flow mediated dilation (FMD). Further, the observation period lasted for 5 years. Two groups were chosen according to the level of BP: the 1st group included the patients with AH (BP level 140/90 mm Hg and higher), the 2nd group consisted of the patients with the normal level of BP (lower 140/90 mm Hg). Results. 78 persons were withdrawn from the study for different reasons during observation period. AH was found in 144 participants (18.8%, 95% CI 16.2-21.7%) — group 1, 620 people of group 2 showed normal BP in 620 (81.2%; 95% confidence Interval (CI) 78.3–83.8%). In group 1 FMD was 7.5 (5.3; 9.9)%, in group 2 — 12.3 (10.2; 13.4)% (p&lt;0,05). Based on the data of univariate analysis of male sex (odds ratio (OR) 10.8; 95% CI 7.63–15.28), body mass index (BMI) &gt; 25 kg/m2 (OR 7.17; 95% CI 5.65–9.10), smoking (OR 5.61; 95% CI 4.5–6.98), high normal BP (OR 10.68; 95% CI 6.92– 14.51) and FMD &lt;10% (OR 3.49; 95% CI 2.19–5.57) were significant risk factors of AH. The results of multivariate analysis BMI &gt; 25 kg/m2 , high normal BP and FMD &lt; 10% were independent risk factors. Conclusion. Endothelial dysfunction is an independent risk factor of AH in young patients with initially normal level of AD during 5 years.

Omega-3 Polyunsaturated Fatty Acids Protect Against Cigarette Smoke-Induced Oxidative Stress and Vascular Dysfunction.

In cigarette smokers endothelial dysfunction, measured by flow-mediated dilation (FMD), precedes cardiovascular disease (CVD) and can be improved by supplementation with n - 3 polyunsaturated fatty acids (PUFAs). We developed a mouse model of cigarette smoke (CS)-induced endothelial dysfunction that resembles impaired FMD observed in human cigarette smokers and investigated the mechanism by which n - 3 PUFAs mediate vasoprotection. We hypothesized that loss of nitric oxide (NO)-dependent vasodilation in CS-exposed mice would be prevented by dietary n - 3 PUFAs via a decrease in oxidative stress. C57BL/6 mice were fed a chow or n - 3 PUFA diet for 8 weeks and then exposed to mainstream CS or filtered air for 5 days, 2 h/day. Mesenteric arterioles were preconstricted with U46619 and dilated by stepwise increases in pressure (0-40 mmHg), resulting in increases in flow, ± inhibitor of NO production or antioxidant, Tempol. Markers of oxidative stress were measured in lung and heart. CS-exposed mice on a chow diet had impaired FMD, resulting from loss of NO-dependent dilation, compared with air exposed mice. Tempol restored FMD by normalizing NO-dependent dilation and increasing NO-independent dilation. CS-exposed mice on the n - 3 PUFA diet had normal FMD, resulting from a significant increase in NO-independent dilation, compared with CS-exposed mice on a chow diet. Furthermore, n - 3 PUFAs decreased two CS-induced markers of oxidative stress, 8-epiprostaglandin-F2α levels and heme oxygenase-1 mRNA, and significantly attenuated CS-induced cytochrome P4501A1 mRNA expression. These data demonstrate that dietary n - 3 PUFAs can protect against CS-induced vascular dysfunction via multiple mechanisms, including increasing NO-independent vasodilation and decreasing oxidative stress.

A case of primary aldosteronism presenting as non-ST elevation myocardial infarction

A case of primary aldosteronism presenting as non-ST elevation myocardial infarction

Assessment of Vascular Reactivity in the Peripheral and Coronary Arteries by Cine 3T-Magnetic Resonance Imaging in Young Normotensive Adults after Surgery for Coarctation of the Aorta

This study aimed to investigate whether coarctation of the aorta in infancy indicates an altered vascular reactivity in the peripheral and coronary arteries apart from the secondary effect of hypertension or other complications of the disease. Patients with repaired coarctation of the aorta have a high prevalence of premature cardiovascular complications. The etiology still is not fully understood, and the cause is most likely multifactorial. Endothelial function was assessed by peripheral flow mediated dilation (FMD) and coronary flow reserve (CFR) in a study of 10 control subjects and 10 patients with a successfully repaired coarctation of the aorta (mean age, 20.9 years; 20.5 years after repair). No one had re- or rest-coarctation of the aorta, hypertension, pathologic blood pressure response during exercise, or associated cardiac malformations such as bicuspid aortic valve. CFR was achieved by phase-contrast velocity encoding cine magnetic resonance imaging in the coronary sinus before and during infusion with adenosine (0.14mg/kg/min). FMD was measured in the brachial artery before and after 5min of arterial occlusion. A normal CFR and FMD was found in both groups. Most studies have been conducted with large, unselected groups. The current study group represented the best outcome of the coarctation spectrum (i.e., patients with no evidence of a residual gradient across the coarctation site or systemic hypertension). The findings reassuringly suggest that significant endothelial dysfunction and atherosclerotic changes were not present in this selected cohort.

Abstract 145: Clinical and Vascular Changes Related to Endothelial Dysfunction in Treated Hypertensive Patients

Background: It is widely recognized that endothelial dysfunction is commonly associated to hypertension but the parameters linked to this condition among hypertensive subjects are not established yet. Objective: To identify clinical, metabolic and vascular changes related to endothelial dysfunction in treated hypertensive patients Methods: A cross-sectional study was carried out to evaluate hypertensive patients on stable drug therapy over at least 4 weeks, both genders, aged 40-70 years. Blood pressure (BP) was measured by oscilometric method, and vascular tests were performed using high-resolution ultrasonography for brachial flow-mediated dilation (FMD), Sphygmocor to obtain central hemodynamic parameters and Complior SP to determine carotid-femoral pulse wave velocity (cfPWV) which was normalized by mean BP (cfPWV-N). The 10-year risk for general cardiovascular disease from Framingham Heart Study was used to calculate vascular age. Patients (n=81) were distributed into two groups according to brachial FMD values: FMD &lt; 10% (n=54) or FMD &gt;= 10% (n=27). Results: The mean age was not different among the groups (55.1±8.3 vs 55.7±7.0 years, p&gt;0.05). Systolic BP (142±19 vs 137±13, p&gt;0.05) and diastolic BP (94±14 vs 92±13 mmHg, p&gt;0.05) were similar in the two groups. The group with FMD &lt; 10% presented greater carotid media-to-lumen ratio (0.12±0.03 vs 0.10±0.02, p&lt;0.05), vascular age (77±14 vs 70±12, p&lt;0.05) and higher duration of hypertension (9.9±9.19 vs 5.9±4.2, p&lt;0.05) than the group with normal FMD. There was an inverse correlation between FMD and vascular age (r=-0.235, p&lt;0.05). No significant differences in biochemical variables, parameters of vascular stiffness and number of criteria of metabolic syndrome were observed. Conclusion: The characterization of endothelial dysfunction in treated hypertensive patients was not related to age but it was more associated to duration of hypertension and vascular age. There was no evidence of vascular stiffness in these patients but the increased carotid media-to-lumen ratio may indicate the beginning of atherosclerotic process.

388 BRACHIAL FLOW-MEDIATED DILATION AS A PREDICTOR OF TARGET ORGAN DAMAGE IN ESSENTIAL HYPERTENSIVE PATIENTS

Background: We found impaired brachial flow-mediated dilation (FMD) was associated with the number of target organ damage (TOD). The purpose of this study was to evaluate the predictive value of FMD for the progression of TOD in essential hypertension. Methods and results: Endothelium-dependent brachial FMD was measured in 280 adults (mean age 59 ± 10, men 58%) in 2007. At the third year examination (from May to December 2010), 204 patients were approached for participation in our study. Patients were divided into two groups as following: FMD>10 (normal FMD group) and FMD<10 (impaired FMD group). In patients with 0-1TOD(n = 124) in 2007, impaired FMD group(n = 65) led to thicker intima-media thickness(IMT) of common carotid artery (0.73 ± 0.15 vs 0.66 ± 0.09, P = 0.001), increased carotid to femoral pulse wave velocity (cf-PWV:14.6 ± 3.3 vs 13.2 ± 2.9, P = 0.012), decreased FMD (8.0 ± 3.9 vs 10.0 ± 4.0, P = 0.007) and increased urinary albumin creatinine ratio (lgUACR:0.35 ± 0.70 vs 0.12 ± 0.49, P = 0.035) than normal FMD group(n = 59) in 2010. Impaired FMD also led to increasing the number of TOD (1.91 ± 1.01 vs 1.36 ± 1.08,P = 0.004) in 2010. While in the patients with 2-4TOD (n = 75) in 2007, there was no difference in TOD progression between impaired and normal FMD groups in 2010. In addition, TOD number increasing was associated with higher pulse pressure (β = 0.274, P = 0.001), higher LDL-C (β = 0.274, P = 0.006) and worse FMD (β = −0.167, P = 0.048) in stepwise multivariate regression analysis. Conclusions: FMD is a predictor of future TOD progression in the early stage of essential hypertensive patients, but has little predictive value in the late stage of TOD.

Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise

Associations between high particulate matter (PM) pollution and increased morbidity and mortality from coronary heart disease have been identified. This study assessed leukotriene (LT) participation in PM-induced vascular endothelial dysfunction. Ten healthy males exercised 4 times for 30 min in both high PM (550,286 ± 42,004 particles·cm−3) and low PM (4571 ± 1922 particles·cm−3) after ingesting placebo (PL) or 10 mg montelukast (MK; half-life 3–6 h), a leukotriene receptor antagonist. Brachial artery flow-mediated dilation (FMD) was measured pre- and 30 min, 4 h, 24 h post-exercise. No basal brachial artery vascoconstriction was evident from high PM exercise. High PM blunted FMD, whereas high PM MK, low PM PL, and low PM MK demonstrated normal FMD (p < .003). Change in FMD (pre- to post-exercise) for high PM PL was different than for high PM MK, low PM PL, and low PM MK at 30 min post-exercise (p < .007). At 4 h, high PM MK FMD blunting increased (p = .1). At 24 h, high PM FMD blunting persisted (p < .05); no difference was observed between high PM PL or MK treatment, but was different that low PM PL/MK treatments (p < .05). MK blocked high PM post-exercise FMD blunting and maintained normal response, suggesting that leukotrienes are involved in PM-initiated vascular endothelial dysfunction.

Early Effects on Endothelial Function of Atorvastatin 40 mg Twice Daily and Its Withdrawal

Combined hyperlipidemia is associated with endothelial dysfunction. Atorvastatin has lipid-lowering and pleiotropic properties, including a protective effect on endothelial function. This study investigated the short- and medium-term effects of therapy with atorvastatin and of its discontinuation on lipid lowering and endothelial function. In 33 patients with combined hyperlipidemia who had been randomized and treated for 6 weeks with 40 mg of atorvastatin twice daily (n = 23) or placebo (n = 10), fasting lipid levels and flow-mediated dilation (FMD) of the brachial artery were measured at baseline, after 12 hours, 1 week, and 6 weeks during therapy, and 36 hours after discontinuation of therapy. Thereafter, all patients received 20 mg/day of atorvastatin for another 6 weeks. In the atorvastatin group, low-density lipoprotein cholesterol was decreased by 30% and 46% after 1 and 6 weeks, respectively (p <0.0001 for the 2 comparisons). In patients who already showed an impaired FMD at the beginning of the study (n = 15), atorvastatin caused a significant improvement in FMD, from 2.6% at baseline to 4.0% and 6.3% after 1 and 6 weeks, respectively (p <0.05 and <0.001). Thirty-six hours after withdrawal of atorvastatin, the FMD in this group decreased again to 2.8% (p <0.05), whereas low-density lipoprotein cholesterol level remained unchanged. The 6 patients with normal FMD at baseline showed no improvement in FMD during therapy or any decrease after withdrawal of the drug. In conclusion, only patients with endothelial dysfunction profit from high-dose atorvastatin treatment. When the treatment is abruptly discontinued, the effect on FMD disappears in 36 hours.

Peroxynitrite reduces the endothelium-derived hyperpolarizing factor component of coronary flow-mediated dilation in PECAM-1-knockout mice

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is capable of transducing signals in endothelial cells exposed to shear; however, the biological consequences of this signal transduction are unknown. Because shear stress elicits flow-mediated dilation (FMD), we examined whether steady-state FMD in mouse coronary arteries (MCAs) is affected in the PECAM-1 knockout (KO) mouse. MCAs were isolated from wild-type (WT) or KO mice and prepared for videomicroscopy, histofluorescence, Western blotting, and immunohistochemistry. FMD was examined in the absence and presence of N(omega)-nitro-l-arginine methyl ester (l-NAME) and l-NAME+indomethacin (INDO). FMD was reduced in KO relative to WT MCAs, but the l-NAME-inhibitable portion of FMD was similar between the two. The INDO-sensitive component of FMD was diminished in KO MCAs. In contrast, the residual component of dilation, presumably because of endothelium-derived hyperpolarizing factor (EDHF), was abolished in KO MCAs. Histofluorescence showed relatively more superoxide (O2-.; oxy-ethidium fluorescence) and peroxide production (dihydrochlorofluorescene fluoresecence) in KO MCAs at rest. Flow augmented O2-. and peroxide production in WT MCAs but had little effect on KO MCAs. Enhanced nitric oxide generation was observed in arteries from KO mice, accompanied with increased eNOS S1177 phosphorylation. In vessels from KO mice, treatment with ebselen decreased peroxynitrite (ONOO-) formation and improved the reduced FMD, largely due to restoration of the presumed EDHF component. These results suggest that PECAM-1 is necessary for normal FMD in the mouse coronary circulation. In the absence of this adhesion and signaling molecule, ONOO- production is increased concomitant with a reduction in both the EDHF and INDO-sensitive components of FMD.

The Effect of Ciprofibrate on Flow-Mediated Dilation and Inflammatory Markers in Patients with Combined Hyperlipidemia

Impairment of flow-mediated dilation (FMD) has been shown to be associated with hypercholesterolemia and hypertriglyceridemia and reduction of cholesterol and/or triglyceride levels can improve FMD. In hyperlipidemia the role of inflammatory substances on endothelial function requires further clarification. In patients with combined hyperlipidemia (n = 29), the capacity of FMD was weaker whereas the levels of interleukin (IL)-lalpha, tumor necrosis factor alpha (TNFalpha), soluble intercellular adhesion molecule (sICAM), and fibrinogen were higher compared to normolipemic controls with normal FMD adjusted for age and sex. Patients were randomized to a diet-only or to a ciprofibrate treatment group. After 8 weeks FMD levels rose significantly both in the diet-only (10.2%) and the ciprofibrate treatment (79.4%) groups. In the diet-only group improvement of FMD was significantly associated with the reduction of triglyceride (by 15.9%) and cholesterol (6.9%) levels. The much larger improvement of FMD due to ciprofibrate therapy was accompanied by significant reductions of cholesterol (by 14.4%), fibrinogen, IL-1alpha, and sICAM levels and by significant increase of high-density lipoprotein (HDL) cholesterol concentration, but the change in FMD correlated only with the reduction of the cholesterol level. In line with previous data the authors emphasize that improvement of FMD in patients with combined hyperlipidemia treated with diet and/or ciprofibrate is linked directly to the reduction of cholesterol and triglyceride concentrations rather than to changes in the level of the investigated inflammatory markers.

Type 2 diabetes is associated with impaired endothelium-dependent, flow-mediated dilation, but impaired glucose metabolism is not: The Hoorn Study

Background: Type 2 diabetes (DM2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. Impaired endothelial synthesis of nitric oxide (NO) is an important feature of atherothrombosis and can be estimated from endothelium-dependent flow-mediated dilation (FMD). It is controversial whether or not FMD is impaired in DM2 and IGM. We investigated this issue in a population-based setting. Methods and results: In the study population ( n=650; 246 with normal glucose metabolism (NGM), 135 with IGM and 269 with DM2; mean age: 67.6 years), FMD and endothelium-independent nitroglycerine-mediated dilation (NMD) were ultrasonically estimated from the brachial artery and expressed as the absolute change in diameter in mm. The increase in diameter (mean ± standard deviation) in NGM, IGM and DM2 was 0.19±0.15, 0.19±0.18 and 0.13±0.17 for FMD and 0.45±0.21, 0.43±0.24 and 0.45±0.25 for NMD. After adjustment for age, sex, baseline diameter and percentage increase in peak systolic velocity, DM2, as compared to NGM, remained associated with impaired FMD (regression coefficient β (95%CI)) as compared to NGM, −0.06 mm (−0.09 to −0.03). IGM was not associated with impaired FMD ( β, 0.01 mm (−0.02 to 0.04)). Additional adjustment for conventional cardiovascular risk factors did not alter these associations. Hyperglycemia or hyperinsulinemia explained 2% of the association between DM2 and FMD. NMD was not associated with glucose tolerance. Conclusions: This study shows that DM2 is independently associated with impaired FMD. Hyperglycemia and hyperinsulinemia contribute minimally to this association. Impaired FMD may therefore, in part, explain the increased cardiovascular disease risk in DM2, whereas the normal FMD in IGM suggests that other forms of endothelial dysfunction are important in explaining the increased cardiovascular disease risk in IGM.

Detection of endothelial dysfunction with brachial artery ultrasound scanning

The role of the endothelium in human disease recently has become the focus of intense scientific investigation. Impaired endothelial function is associated with a number of disease states, including cardiovascular disease (CVD) and its major risk factors. Endothelial dysfunction precedes overt vascular disease by years and may itself be a potentially modifiable CVD risk factor. Although no gold standard for the measurement of endothelial function exists, the measurement of flow-mediated dilation (FMD) in the brachial artery, assessed with Doppler ultrasonography, is the most studied method and shows the most promise for clinical application. It is a well-tolerated, noninvasive, and low-risk procedure. Brachial artery FMD after transient vascular occlusion may serve as an index of nitric oxide bioavailability, and its impairment correlates with coronary arterial abnormalities. These factors, with the wide availability of vascular ultrasound scanning in clinical practice, make brachial artery FMD an attractive screening tool for endothelial dysfunction. Present limitations of this procedure include the lack of a consensus definition of normal FMD and the variability among centers in both procedural technique and image analysis. However, these limitations are likely to be overcome with increasing experience and advances in technology, and with further refinements, the measurement of brachial artery FMD will likely become the clinical technique of choice for the evaluation of endothelial disease.