Measurement Of Flow-mediated Vasodilation Research Articles

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

The reproducibility of brachial artery flow-mediated vasodilatation (FMD) is limited by the operator dependence of most measurement 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. 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%. 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.

Low Testosterone Level Is an Independent Determinant of Endothelial Dysfunction in Men

We investigated whether a low plasma testosterone level is related to endothelial dysfunction in men with coronary risk factors. One hundred and eighty-seven consecutive male outpatients (mean age+/-SD: 47+/-15 years) who underwent measurement of flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography were enrolled. The relationship between plasma hormones and FMD was analyzed. Total and free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were significantly correlated with %FMD (r=0.261, 0.354 and 0.295, respectively; p<0.001), while estradiol and cortisol were not. %FMD in the highest quartile of free testosterone was 1.7-fold higher than that in the lowest quartile. Multiple regression analysis revealed that total and free testosterone were related to %FMD independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus and smoking (beta=0.198 and 0.247, respectively; p<0.01), and were independent of age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, smoking and nitroglycerin-induced dilation (beta=0.196 and 0.227, respectively; p<0.01). DHEA-S was not significantly related to %FMD in multivariate analysis. In conclusion, a low plasma testosterone level was associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium.

Arterial compliance influences the measurement of flow-mediated vasodilation, but not acetylcholine-mediated forearm blood flow: The prospective investigation of the vasculature in uppsala seniors (PIVUS) study

Objectives Flow-mediated vasodilation (FMD) is low even in healthy elderly and therefore relations between FMD and cardiovascular risk factors might be hard to evaluate in the elderly. Using data from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we investigated if a reduced arterial distensibility could influence FMD measurements. Methods In the population-based PIVUS study (1016 subjects aged 70), assessments of arterial distensibility by ultrasound in the carotid artery (CCA) and FMD were performed. Endothelium-dependent vasodilation was also evaluated with the invasive forearm technique with acetylcholine (EDV) and by pulse wave analysis following terbutaline injection. A poor CCA distensibility was defined as <25th percentile in the healthy part of the population ( n = 131). Results FMD was significantly related to the Framingham risk score only in those with a good CCA distensibility ( r = −0.16, p = 0.0081 versus r = −0.06, p = 0.17 in those with a poor CCA distensibility, p = 0.0001 for difference). In contrast, the relationship between EDV and coronary risk was not affected by CCA distensibility ( r = −0.11, p = 0.018 versus r = −0.13, p = 0.027). Conclusions A reduced CCA distensibility could in part explain the low FMD values in the elderly. FMD correlated to the Framingham risk score only in those with a good CCA distensibility, exemplifying a limitation of the use of FMD in elderly populations. On the contrary, EDV was not affected by arterial stiffness.

Anti-thrombotic effect of strawberries

Because of the high mortality, prevention of arterial thrombotic disease has top priority in developed countries. As inappropriate diet is known to predispose to acute thrombotic events, regular intake of an anti-thrombotic diet may offer a convenient and effective method of prevention. As part of a systematic investigation into the anti-thrombotic effect of fruits and vegetables, strawberry varieties were tested in this study. An in vitro platelet function test (haemostatometry) was used for screening strawberry filtrates. Those that showed significant antiplatelet effect were further assessed with a laser-induced thrombosis test in mice. Measurement of flow-mediated vasodilation in the femoral artery of mice reflected the effect on the vascular endothelium. Correlation between the effects on platelet reactivity in vitro and the antioxidant activity (hypoxanthine/xanthine oxidase test) or phenolic compound content was assessed. Strawberry varieties KYSt-4 (Nohime), KYSt-11 (Kurume IH-1) and KYSt-17 (Kurume 58) showed significant antiplatelet activity both in vitro and, after oral administration, in vivo. Both KYSt-11 and KYSt-17, but not KYSt-4, significantly reduced flow-mediated vasodilation; that is, caused endothelial dysfunction. Antiplatelet activities were heat stable. Significant correlation was found between antiplatelet and antioxidant activities (P=0.049, R=0.23) or total phenolic compounds (P=0.0096, R=0.36). Of the tested strawberry varieties, KYSt-4, KYSt-11 and KYSt-17 showed significant anti-thrombotic effect. The dual mechanism of the effect may involve a direct inhibition of both platelet function and antioxidant activities.

Effects of rosuvastatin on endothelial function in patients with familial combined hyperlipidaemia (FCH)

ABSTRACTObjective: Although several studies have reported a positive effect of statins on endothelial vasoreactivity, most studies performed in subjects with type 2 diabetes mellitus report no effect at all. This lack of effect may be related to the existence of insulin resistance, or to insufficient lowering of atherogenic (apo)lipoproteins. Therefore, we tested in this study whether treatment of insulin resistant familial combined hyperlipidaemia (FCH) patients with a high dose (40 mg/day) of the potent rosuvastatin was able to improve endothelial function, without necessarily improving insulin sensitivity.Research design and methods: In a double-blind randomised crossover study, 18 subjects with FCH (without evident cardiovascular disease, mean [standard deviation] age 54 [7] years) underwent a 4‐week run-in period after which they were randomised to treatment with placebo once daily for 12 weeks, followed by rosuvastatin 40 mg/day for 12 weeks or vice versa. Endothelial function was determined after 8 and 12 weeks of both treatment periods, respectively, by measurement of flow-mediated vasodilation (FMD) using high-resolution ultrasound and by measurement of vasodilator response to intrabrachial acetylcholine (Ach) by venous occlusion plethysmography (forearm blood flow [FBF]).Results: Plasma levels of lipids, (apo)lipoproteins and high-sensitivity C‐reactive protein (hsCRP) improved significantly after rosuvastatin therapy compared to placebo. However, rosuvastatin had no effect on homeostasis model assessment (HOMA)-indices or on vasodilator responses to intra-brachial acetylcholine-infusion (FBF-ratio increased from a mean of 1.28 [SD: 0.46] to 5.82 [3.44] after rosuvastatin and from 1.33 [0.67] to 5.99 [3.89] after placebo, p = 0.35). Endothelium-dependent FMD was also unchanged (1.6% [3.1%] vs. 3.2% [3.5]%, p = 0.56 rosuvastatin vs. placebo, respectively).Conclusion: In patients with FCH, a 12‐week treatment of rosuvastatin 40 mg/day did not improve endothelial function (either in large conduit vessels or in resistance vessels), despite significant improvements in plasma lipids, (apo)lipoproteins. and low-grade inflammation.

Colombian Study to Assess the Use of Noninvasive Determination of the Endothelium-Mediated Vasodilation (CANDEV) II. Does Location of the Occlusion Device Affects the Accuracy of the Diagnosis?

Endothelial dysfunction (ED), which is often evaluated by flow-mediated vasodilation (FMV) in the brachial artery, has been postulated as a predictor of cardiac events. Although the upper and forearm location of the occlusion device have been used for FMV evaluation, currently there is no consensus whether they provide the same information. The main goal of this study was to evaluate if both techniques have the same accuracy to differentiate subjects with and without cardiovascular risk factors (CRFs). A cross-sectional study in 124 subjects was performed. The volunteers were divided in two groups: 62 subjects (20 women and 42 men) with at least one CRF and 62 (20 women and 42 men) healthy subjects without CRFs. FMV measurements using the cuff in the upper arm and forearm with intervals of 30 min were taken. In all subjects, %FMV with the cuff located in the upper arm was 10.13 +/- 4.5 and 9.8 +/- 4.1 with the cuff located below the elbow. In healthy subjects without CRFs the %FMV in the upper arm was 12.19 +/- 4.0 versus 12.31 +/- 3.4 in the upper forearm, in CRF subjects it was 8.08 +/- 4.0 vs 7.29 +/- 3.2., respectively. FMV was not affected by the location of the cuff in maintaining the test ability and accuracy to differentiate subjects with and without CRFs.

Effect of tirofiban on percutaneous coronary intervention-induced endothelial dysfunction in patients with stable coronary artery disease

Recent studies demonstrated that glycoprotein (GP) IIb/IIIa receptor antagonists improve endothelial dysfunction of forearm resistance vessels in patients with stable coronary artery disease. However, it remains unclear whether these findings can be extended to the conductance vessel level. In this study, we aimed to evaluate the acute effect of tirofiban on endothelial function of arterial conductance vessels in patients undergoing percutaneous coronary intervention (PCI). Endothelial function was examined by ultrasonographic measurement of flow-mediated vasodilation (FMD) of the brachial artery. Endothelium-independent vasodilation was determined in response to nitroglycerin. Sixty-six patients who underwent PCI were included in the study. Thirty-three patients received a bolus of 10 microg/kg body weight of tirofiban, whereas 33 patients who did not receive tirofiban served as the control group. FMD was measured in all patients before and 30 minutes after PCI. Tirofiban significantly improved FMD (6.0 +/- 0.4% before vs 7.8 +/- 0.5% after PCI, p <0.0001), whereas FMD deteriorated in patients in the control group (6.1 +/- 0.6% before vs 4.7 +/- 0.7% after PCI, p = 0.006). Nitroglycerin-induced dilation remained unaltered in response to PCI. In another group of 11 patients with coronary artery disease, FMD did not change after coronary angiography without coronary intervention. In conclusion, PCI induces endothelial dysfunction in forearm conductance vessels that can be reversed with tirofiban.

Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response

The ability to assess endothelial function non-invasively with B-mode ultrasound has lead to its widespread application in a variety of studies. However, the absolute values obtained using this approach vary considerably across studies. We studied whether technical aspects of the methodology can explain the wide variety in absolute values across studies. A literature search was performed to identify published reports on flow-mediated vasodilatation (FMD) of the brachial artery published between 1992 and 2001. Information on type of equipment (wall track/B-mode), location of the measurement (antecubital fossa/upper arm), occlusion site (lower/upper arm), occlusion duration (min), and occlusion pressure was extracted. Patient characteristics were also extracted. For the healthy populations, mean FMD varied from 0.20 to 19.2%; for the coronary heart disease (CHD) patients FMD varied from -1.3 to 14%; for subjects with diabetes mellitus FMD varied from 0.75 to 12%. Compared with occlusion at the upper arm, lower arm occlusion was related to decreased FMD (mean difference in FMD -2.47%; 95% CI 0.55-4.39). An occlusion duration of > or =4.5 min was related to an increased FMD compared with an occlusion time of < or =4 min (mean difference 1.30%; 95% CI 0.35-2.46). These findings were adjusted for other technical aspects of the methodology and for differences in risk factors between populations. Mean FMD differs widely between studies. There is a great overlap between populations (healthy, CHD, diabetics). Our findings suggest that the technical aspects of the measurements, the location, and the duration of the occlusion may explain some of these differences, whereas type of equipment, location of the measurement, and occlusion pressure do not.

Effects of low-dose combination therapy with an angiotensin-converting enzyme inhibitor and a diuretic on flow-mediated vasodilation in hypertensive patients: a 6-month, single-center study

Background Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a diuretic has been shown to be highly effective in hypertension. Clinical trials have demonstrated that ACE inhibitors may improve endothelial cell dysfunction in hypertension. However, the effectiveness of the combination treatment in endothelial cell dysfunction is unknown. Objective This study investigated the effects of a new low-dose combination, perindopril 2 mg plus indapamide 0.625 mg, on brachial artery flow–mediated vasodilation (FMD) and left ventricular diastolic function in hypertension. Methods Patients aged 18 to 75 with newly diagnosed stage I or II hypertension were eligible. Endothelium-dependent brachial artery FMD and endothelium-independent vasodilation were assessed at baseline. Patients were treated with oral perindopril 2 mg plus indapamide 0.625-mg tablets once daily for 6 months. FMD measurements were then repeated. Percentage changes in FMD from baseline to 6 months, as well as left ventricular diastolic function parameters (isovolumic relaxation time [IVRT] and mitral diastolic E-wave deceleration time [EDT]), indicated the effectiveness of the intervention. Results Twenty-nine Turkish patients were enrolled (17 women, 12 men; mean [SD] age, 54.5 [9.5] years [range, 38–75 years]). The mean (SD) baseline FMD was 7.00% (2.39%) (endothelial cell dysfunction) and increased significantly to 8.68% (2.78%) at 6 months ( P = 0.02); FMD improved in 15 patients (51.7%). At baseline and 6 months of therapy, mean (SD) IVRT was 101.7 (12.4) ms and 95.5 (7.7) ms, respectively ( P<0.001), and EDT was 234.7 (33.9) ms and 217.9 (25.6) ms, respectively ( P<0.001). Conclusions In this small sample of hypertensive patients, a low-dose combination ACE inhibitor and diuretic significantly improved brachial artery FMD and left ventricular diastolic function. The improvement in FMD values was independent of the stage of hypertension. These findings suggest a relationship between improvement in endothelial cell function and diastolic function.

Differential blood flow in uterine, ophthalmic, and brachial arteries of preeclamptic women

OBJECTIVE: To develop a method that employs noninvasive, pulsed Doppler ultrasonography combined with measurement of flow-mediated vasodilation to evaluate characteristic endothelial dysfunction in various degrees of preeclampsia. METHODS: Uterine, ophthalmic, and brachial arterial blood flow of 99 pregnant women (control group [ n = 32], non-preeclamptic intrauterine growth restriction group ( n = 15), mild preeclampsia group [ n = 25], and severe preeclampsia group [ n = 27]) were evaluated by pulsed Doppler ultrasound or flow-mediated vasodilation. RESULTS: Uterine, orbital, and brachial circulation were altered in preeclampsia, whereas no significant differences were observed between the non-preeclamptic intrauterine growth restriction and control groups. Pulsatility index in the uterine arteries of preeclamptic women with intrauterine growth restriction was approximately three-fold higher than that of normotensive women with or without intrauterine growth restriction. The peak ratio (defined to quantify characteristic flow velocity waveform) of the ophthalmic artery of hypertensive women was significantly higher than that of normotensive women. Flow-mediated vasodilation in the brachial artery of preeclamptic women with intrauterine growth restriction was significantly lower than that in preeclamptic women without intrauterine growth restriction. Among preeclamptic women, elevation of the resistance in the uterine artery and reduced flow-mediated vasodilation were closely correlated to intrauterine growth restriction, whereas the elevated peak ratio of the ophthalmic artery was dependent on hypertension, irrespective of the presence of intrauterine growth restriction. CONCLUSION: Ultrasound evaluation of uterine and orbital circulation and flow-mediated vasodilation of the brachial artery helps differentiate the degree and severity of preeclampsia.

Measurement of flow mediated vasodilation (FMD) using kalman-filtering

Brachial artery flow-mediated vasodilation is increasingly used as a measure of endothelial function. High resolution ultrasound provides a noninvasive method to observe this flow-mediated vasodilation by monitoring the diameter of the artery over time. In the past, the diameter had to be measured in tedious postprocessing routines, usually by the examiner himself. We present a system, which is able to process ultrasound rf-data in realtime. On that system, we implemented a kalman filter, which makes the tracking of both vessel walls possible. The diameter can be calculated accurately, taking into account process noise as well as measurement noise.