{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:25:54Z","timestamp":1792193154629,"version":"4.4.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper aims to assess FMD values in apparently healthy individuals and provides reference values to facilitate wider clinical use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In 1,579 apparently healthy individuals (aged 18\u201376), fasted FMD values (data from 44 studies, 6 institutions, 22 operators) were normally distributed and inversely univariately correlated with age, body mass index, glucose, cholesterol, blood pressure, and brachial artery (BA) diameter. Significant multivariate predictors of FMD were age (\u22120.4%\/decade), BMI (0.04%\/kg\/m2), smoking (\u22120.7%), and BA diameter (\u22120.44%\/mm) that together explained 19% of the variability independent of operator, institution or ultrasound machine. Individuals in the high FMD tertile (&amp;gt;6.8%) were younger, had smaller BA diameter, lower blood pressure and cholesterol. In individuals with low- and intermediate fatal cardiovascular risk (SCORE), 26% and 53% of individuals, respectively, had FMD values in the low tertile (&amp;lt;5.4%). After adding data from 385 patients with stable coronary artery disease (CAD), ROC analysis (c = 0.841, P &amp;lt; 0.001) showed that FMD of &amp;gt;6.5% excluded CAD (95% sensitivity; 60% specificity) and FMD &amp;lt;3.1% excluded 95% healthy individuals (95% specificity, 31% sensitivity). A meta-analysis and meta-regression of 82 clinical trials (11 countries, n = 3,509) using similar FMD methodology showed that despite considerable heterogeneity (I2 = 0.97) FMD in healthy individuals was on average 6.4% (95%CI: 6.2%, 6.7%) with no significant differences between countries but a significant age-dependent decline (\u22120.3%\/decade, R2 = 0.13).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We provide an age-adapted frame of FMD reference intervals in apparently healthy individuals for use as a biomarker of cardiovascular health. As the degree of vascular endothelial function integrates environmental and genetic factors with classical CV risk factors, FMD may more comprehensively classify individuals with and without standard modifiable cardiovascular risk factors and serve as a target for cardiovascular prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvac095","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T14:31:01Z","timestamp":1655389861000},"page":"283-293","source":"Crossref","is-referenced-by-count":112,"title":["Flow-mediated dilation reference values for evaluation of endothelial function and cardiovascular health"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-8995","authenticated-orcid":false,"given":"Christian","family":"Heiss","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , UK"},{"name":"Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Vascular Department, Surrey and Sussex Healthcare NHS Trust, East Surrey Hospital , Redhill , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-402X","authenticated-orcid":false,"given":"Ana","family":"Rodriguez-Mateos","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, School of Life Course and Population Sciences, King's College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Bapir","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-3122","authenticated-orcid":false,"given":"Simon S","family":"Skene","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Sies","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology and Biochemistry I, Medical Faculty, Heinrich Heine University D\u00fcsseldorf , D\u00fcsseldorf , Germany"},{"name":"Leibniz Research Institute for Environmental Medicine, Heinrich Heine University D\u00fcsseldorf , D\u00fcsseldorf , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0060-1052","authenticated-orcid":false,"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University D\u00fcsseldorf , D\u00fcsseldorf , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"2023031717471135900_","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/cvr\/cvaa085","article-title":"Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis","volume":"117","author":"Alexander","year":"2021","journal-title":"Cardiovasc Res"},{"key":"2023031717471135900_","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cell.2020.11.034","article-title":"Hallmarks of health","volume":"184","author":"Lopez-Otin","year":"2021","journal-title":"Cell"},{"key":"2023031717471135900_","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1089\/ars.2014.6158","article-title":"Central role of eNOS in the maintenance of endothelial homeostasis","volume":"22","author":"Heiss","year":"2015","journal-title":"Antioxid Redox Signal"},{"key":"2023031717471135900_","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.atherosclerosis.2015.05.007","article-title":"The role of vascular biomarkers for primary and secondary prevention. 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