Haruka Morimoto

A novel noninvasive and simple method for assessment of endothelial function: Enclosed zone flow-mediated vasodilation (ezFMD) using an oscillation amplitude measurement

BACKGROUND It is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. Recently, we developed a new noninvasive method for measurement of vascular response to reactive hyperemia in the brachial artery, named enclosed zone flow-mediated vasodilation (ezFMD). The purpose of this study was to determine the validity of ezFMD for assessment of endothelial function. METHODS AND RESULTS We measured ezFMD by a new device using an oscillometric method and conventional FMD using ultrasonography in 306 subjects, including patients with hypertension, dyslipidemia, and diabetes mellitus (218 men and 88 women, 30 ± 16 yr). Univariate regression analysis revealed that ezFMD significantly correlated with age (r = -0.42, P < 0.0001), body mass index (r = -0.13, P = 0.028), systolic blood pressure (r = -0.15, P = 0.009), diastolic blood pressure (r = -0.14, P = 0.011), fasting glucose level (r = -0.27, P = 0.006), smoking (r = -0.21, P = 0.007) and baseline pulse wave amplitude (r = -0.51, P < 0.0001). ezFMD significantly correlated with conventional FMD (r = 0.34, P < 0.0001). Multiple regression analysis revealed that age (P = 0.002), body mass index (P = 0.013), systolic blood pressure (P = 0.009), smoking (P = 0.004) and baseline pulse wave amplitude (P < 0.001) were independent predictors of ezFMD. CONCLUSIONS These findings suggest that measurement of ezFMD, a novel noninvasive and simple method, may be useful for determination of vascular diameter response to reactive hyperemia. Since ezFMD is automatically measured by a device with an oscillometric method, measurement of ezFMD is easier and less biased than that of conventional FMD.

Endothelial Function Assessed by Automatic Measurement of Enclosed Zone Flow-Mediated Vasodilation Using an Oscillometric Method Is an Independent Predictor of Cardiovascular Events

Background A new device for automatic measurement of flow‐mediated vasodilation (FMD) using an oscillometric method has been developed to solve technical problems of conventional FMD measurement. This device measures enclosed zone FMD (ezFMD). The purpose of this study was to evaluate the prognostic value of endothelial function assessed by ezFMD for future cardiovascular events. Methods and Results We measured ezFMD in 272 participants who underwent health‐screening examinations. First, we investigated cross‐sectional associations between ezFMD and cardiovascular risk factors, and then we assessed the associations between ezFMD and first major cardiovascular events (death from cardiovascular causes, stroke, and coronary revascularization). Univariate regression analysis revealed that ezFMD was significantly correlated with age, triglycerides, glucose, smoking pack‐years, estimated glomerular filtration rate, high‐sensitivity C‐reactive protein, and Framingham risk score. During a median follow‐up period of 36.1 months (interquartile range 18.8–40.1 months), 12 participants died (6 from cardiovascular causes), 3 had stroke, 8 had coronary revascularization, and 10 were hospitalized for heart failure. There was no episode of acute coronary syndrome during the study period. Participants were divided into tertiles (low, intermediate, and high) based on ezFMD. Kaplan–Meier curves for first major cardiovascular events among the 3 groups were significantly different (P=0.004). After adjustment for cardiovascular risk factors, the low group was significantly associated with an increased risk of first major cardiovascular events compared with the high group (hazard ratio 6.47; 95% CI 1.09–125.55; P=0.038). Conclusions These findings suggest that endothelial function assessed by ezFMD may be useful as a surrogate marker of future cardiovascular events. Clinical Trial Registration URL: https://upload.umin.ac.jp. Unique identifier: UMIN000004902.

Improvement of novel noninvasive measurement of endothelial function: ezFMD

Endothelial dysfunction is considered as an early event in the development of atherosclerosis and vascular diseases. The conventional non-invasive method used to assess endothelial function, namely, measurement of flow-mediated dilatation (FMD), needs an ultrasound system, which is expensive, and high levels of technical skill. We developed the novel method, measurement of the ezFMD, for the assessment of endothelial function. ezFMD estimates the degree of vasodilatation from the cuff oscillation signal transmitted by the cuff attached to the upper arm. The objective of this study was to clarify the factors influencing the variability of ezFMD, improve the repeatability of ezFMD measurement, and determine the correlation between ezFMD and FMD. We assumed that the following two factors are variable factors, and investigated the following two factors to improve the measurement accuracy. (1) brachial artery occlusion by cuff pressure for oscillation measurement; (2) change of the arterial wall viscosity at dilatation. Repeatability was improved by using the mean pressure method. Also, the correlation was improved by calculating the oscillation amplitude from the pulse wave area. These results suggest that ezFMD has potential for clinical use

Assessment of Lower-limb Vascular Endothelial Function Based on Enclosed Zone Flow-mediated Dilation

This paper proposes a novel non-invasive method for assessing the vascular endothelial function of lower-limb arteries based on the dilation rate of air-cuff plethysmograms measured using the oscillometric approach. The principle of evaluating vascular endothelial function involves flow-mediated dilation. In the study conducted, blood flow in the dorsal pedis artery was first monitored while lower-limb cuff pressure was applied using the proposed system. The results showed blood flow was interrupted when the level of pressure was at least 50 mmHg higher than the subject’s lower-limb systolic arterial pressure and that blood flow velocity increased after cuff release. Next, values of the proposed index, %ezFMDL, for assessing the vascular endothelial function of lower-limb arteries were determined from 327 adult subjects: 87 healthy subjects, 150 subjects at high risk of arteriosclerosis and 90 patients with cardiovascular disease (CAD). The mean values and standard deviations calculated using %ezFMDL were 30.5 ± 12.0% for the healthy subjects, 23.6 ± 12.7% for subjects at high risk of arteriosclerosis and 14.5 ± 15.4% for patients with CAD. The %ezFMDL values for the subjects at high risk of arteriosclerosis and the patients with CAD were significantly lower than those for the healthy subjects (p < 0.01). The proposed method may have potential for clinical application.

Evaluation of Arterial Stiffness during the Flow-Mediated Dilation Test

The paper discusses the arterial stiffness during the flow-mediated dilation (FMD) test The FMD test is a method of evaluating the vascular endothelial function and has been popular as it is non-invasive and readily performed by a skillful ultrasound technician. The FMD test, however, evaluates only the maximal increase in vascular diameter mediated by the increases in blood flow after the release of the occlusive cuff and does not evaluate the arterial viscoelastic properties. This paper thus estimates the log-linearlized stiffness, to evaluate the arterial stiffness properties using the arterial diameter and blood pressure measured in a beat-to-beat manner during the FMD test. To six healthy volunteers, we performed the FMD test to measure the arterial diameter and blood pressure with ultrasound diagnostic imaging equipment and non-invasive continuous arterial blood pressure monitor, respectively. As a result, the maximal vasodilatation ratio of FMD (FMD) was obtained after cuff occlusion. In comparison with the arterial stiffness before the FMD test, the stiffness of the arterial wall is temporarily decrease and increase. It was concluded the the arterial stiffness can be estimated on a beat-to-beat basis during the FMD test.