Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis

Celermajer, D.; Sørensen, Keld E.; Gooch, V; Spiegelhalter, D. J.; Miller, Owen; Sullivan, Ian D.; Lloyd, June K.; Deanfield, John

doi:10.1016/0140-6736(92)93147-f

Cited by 4,326 publications

(3,423 citation statements)

References 27 publications

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“…Measurement of FMD of the brachial artery has been used as a method for assessment of endothelial function in humans 26, 27. In addition, several lines of evidence have demonstrated that FMD could be used not only as an index of endothelial function but also as a prognostic marker of cardiovascular events 11, 28.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

Maruhashi

Soga

Fujimura

et al. 2018

JAHA

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BackgroundThe usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known.Methods and ResultsWe measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed.ConclusionsIn patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification.Clinical Trial Registration URL: http://www.umin.ac.jp. Unique identifier: UMIN000012950.

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Section: Discussionmentioning

confidence: 99%

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

Maruhashi

Soga

Fujimura

et al. 2018

JAHA

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“…[7][8][9] Measurement of flow mediated dilation (FMD) in the brachial artery using ultrasound is noninvasive and is an accurate indicator of NO production. [10][11][12][13] Furthermore, FMD measurement is an accepted index of conduit artery endothelial function, which can serve as an independent predictor of cardiovascular events. 14 Recently, FMD scores for normotensive subjects have been shown to improve on a low salt diet, which is defined as 3 g of salt per day compared with a usual salt diet of 9 g of salt per day.…”

Section: Introductionmentioning

confidence: 99%

Endothelial dysfunction in normotensive salt-sensitive subjects

et al. 2011

J Hum Hypertens

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Salt-sensitivity is associated with a more severe target organ injury and higher mortality, even in normotensive subjects. As endothelial dysfunction is predictive for future cardiovascular events, we evaluated whether normotensive salt-sensitive (NSS) subjects have more pronounced endothelial dysfunction compared with normotensive salt-resistant (NSR) subjects. Normotensive subjects (n ¼ 99, aged 25-50 years) were selected from a rural community in northern China. Salt sensitivity was assigned if mean BP increased by X10% from a 1-week high salt (18 g/day, NaCl) to low-salt diet (3 g/day, NaCl). Endothelial function was assessed by testing the flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, as well as nitrogen oxide (NOx) levels, in plasma and urine at baseline. Blood pressure at baseline was similar between NSS and NSR subjects, but diverged during salt intervention. Furthermore, FMD was significantly lower in 17 NSS subjects (10.2 ± 2.5 vs 14.5 ± 1.6%, P ¼ 0.037) compared with NSR subjects. In addition, average plasma NOx levels were lower in NSS subjects than NSR subjects (61.2 ± 3.23 lM vs 82.5 ± 1.61 lM, P ¼ 0.034). Moreover, Both FMD and plasma NOx levels were negatively correlated with the degree of salt sensitivity (r ¼ À0.435 and r ¼ À0.459, respectively, Po0.01). However, there was no difference in urine NOx between the two groups. Our study indicates that endothelial dysfunction could contribute to the long-term higher levels of target organ injury and higher mortality observed in NSS subjects.

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“…Aging, smoking, obesity, hypertension, dyslipidemia, and diabetes mellitus are well‐known risk factors of endothelial dysfunction 1, 2, 3, 4, 7, 8, 9, 23, 24, 25. We previously showed that ezFMD was significantly correlated with cardiovascular risk factors and endothelial function assessed by FMD in relatively young participants 15.…”

Section: Discussionmentioning

confidence: 99%

“…It is clinically important to assess endothelial function for early detection of atherosclerosis. Several methods have been developed to evaluate endothelial function in humans 3, 4, 5, 6, 7, 8, 9. Measurement of flow‐mediated vasodilation (FMD) in the brachial artery is a noninvasive and broadly applicable method for assessing endothelial function 4, 5, 6, 7, 8, 9.…”

Section: Introductionmentioning

confidence: 99%

“…Several methods have been developed to evaluate endothelial function in humans 3, 4, 5, 6, 7, 8, 9. Measurement of flow‐mediated vasodilation (FMD) in the brachial artery is a noninvasive and broadly applicable method for assessing endothelial function 4, 5, 6, 7, 8, 9. It has been shown that endothelial dysfunction evaluated by FMD is an independent predictor of cardiovascular events 10, 11, 12, 13, 14…”

Section: Introductionmentioning

confidence: 99%

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

Morimoto

Kajikawa

Oda

et al. 2016

JAHA

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BackgroundA 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 ResultsWe 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).ConclusionsThese 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.

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Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis

Cited by 4,326 publications

References 27 publications

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

Endothelial dysfunction in normotensive salt-sensitive subjects

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

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