{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:36:41Z","timestamp":1785818201147,"version":"3.56.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T00:00:00Z","timestamp":1562198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T00:00:00Z","timestamp":1562198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004362","name":"Swiss Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023264","name":"LHW foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100023264","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009396","name":"University Hospital Zurich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004362","name":"Schweizerische Herzstiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009396","name":"Universit\u00e4tsSpital Z\u00fcrich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Dynamic retinal vessel analysis is a novel, non-invasive method to assess microvascular function. The primary aim of this study was to investigate whether retinal microcirculation is impaired in patients with stable coronary artery disease (CAD) compared to patients with heart failure due to CAD (ischaemic heart failure, IHF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A total of 150 adults were enrolled to prospectively assess micro- and macrovasculature. The pre-defined primary outcome was flicker-induced arterial dilatation (FIDa) in patients with CAD [n =\u200940; median age 63 years, interquartile range (IQR) 53\u201370] and IHF (n =\u200940; median age 63 years, IQR 59\u201371) compared to healthy controls (HC, n =\u200970; median age 57 years, IQR 41\u201369). Secondary outcomes included arterial stiffness, flow-mediated dilatation, biomarkers, and ergospirometry parameters. Patients with CAD demonstrated impairment in FIDa that was even more pronounced in patients with IHF (CAD: 1.93 \u00b1 0.28% vs. IHF: 0.41 \u00b1 0.28%, P &amp;lt; 0.001; FIDa in HC: 3.69 \u00b1 0.21%, both P &amp;lt; 0.001) adjusting for age, sex, concomitant medication, and co-morbidities. While pulse wave velocity was increased and flow-mediated dilatation reduced in CAD and IHF patients (both P &amp;lt; 0.001 compared to HC), neither differed between CAD and IHF patients. N-terminal pro-B-type natriuretic peptide (r = \u22120.49, P &amp;lt; 0.001,) and high-sensitivity troponin T (r = \u22120.28, P = 0.003) correlated with FIDa. Intriguingly, mean metabolic equivalents (5.3 \u00b1 2.3 kcal\/kg\/h, n =\u200939) showed a positive correlation with FIDa (r = 0.58, P &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates a decline of retinal arterial function in CAD patients that is significantly more pronounced in the presence of reduced left ventricular ejection fraction, suggesting a continuum of microvascular damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1537","type":"journal-article","created":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T09:13:57Z","timestamp":1562231637000},"page":"988-997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Retinal Microvascular Dysfunction in Patients with Coronary Artery Disease with and without Heart Failure: A\n                    <i>Continuum<\/i>\n                    ?"],"prefix":"10.1093","volume":"21","author":[{"given":"Jens","family":"Barthelmes","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias P.","family":"N\u00e4gele","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]},{"name":"Department of Internal Medicine, Cantonal Hospital Baden Aargau , Baden ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviya","family":"Cantatore","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etibar","family":"Novruzov","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Ludovici","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]},{"name":"Department of Life, Health and Environmental Sciences, University of L'Aquila , L'Aquila ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"von Eckardstein","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ruschitzka","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Sudano","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas J.","family":"Flammer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University Heart Center , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,4]]},"reference":[{"key":"2026011721313575900_ejhf1537-bib-0001","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/eurheartj\/ehx628","article-title":"European Society of Cardiology: cardiovascular disease statistics 2017","volume":"39","author":"Timmis","year":"2018","journal-title":"Eur Heart J"},{"key":"2026011721313575900_ejhf1537-bib-0002","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s13167-017-0099-1","article-title":"Endothelial dysfunction in cardiovascular disease and Flammer syndrome\u2013 similarities and differences","volume":"8","author":"Barthelmes","year":"2017","journal-title":"EPMA J"},{"key":"2026011721313575900_ejhf1537-bib-0003","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1093\/eurheartj\/eht351","article-title":"Endothelial dysfunction over the course of coronary artery disease","volume":"34","author":"Gutierrez","year":"2013","journal-title":"Eur Heart J"},{"key":"2026011721313575900_ejhf1537-bib-0004","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.atherosclerosis.2006.05.005","article-title":"The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort","volume":"192","author":"Shimbo","year":"2007","journal-title":"Atherosclerosis"},{"key":"2026011721313575900_ejhf1537-bib-0005","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1161\/CIRCULATIONAHA.106.678276","article-title":"Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study","volume":"115","author":"Yeboah","year":"2007","journal-title":"Circulation"},{"key":"2026011721313575900_ejhf1537-bib-0006","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/j.jacl.2018.07.015","article-title":"Retinal microvascular dysfunction in hypercholesterolemia","volume":"12","author":"Nagele","year":"2018","journal-title":"J Clin Lipidol"},{"key":"2026011721313575900_ejhf1537-bib-0007","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/eurheartj\/ehx565","article-title":"Retinal microvascular dysfunction in heart failure","volume":"39","author":"Nagele","year":"2018","journal-title":"Eur Heart J"},{"key":"2026011721313575900_ejhf1537-bib-0008","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1161\/CIRCULATIONAHA.116.023446","article-title":"Prediabetes and type 2 diabetes are associated with generalized microvascular dysfunction: the Maastricht study","volume":"134","author":"Sorensen","year":"2016","journal-title":"Circulation"},{"key":"2026011721313575900_ejhf1537-bib-0009","doi-asserted-by":"crossref","first-page":"H631","DOI":"10.1152\/ajpheart.00111.2003","article-title":"Nitric oxide regulates retinal vascular tone in humans","volume":"285","author":"Dorner","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026011721313575900_ejhf1537-bib-0010","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1567-5688(09)71808-2","article-title":"Retinal vessel analysis in hypercholesterolemic patients before and after LDL apheresis","volume":"10","author":"Reimann","year":"2009","journal-title":"Atheroscler Suppl"},{"key":"2026011721313575900_ejhf1537-bib-0011","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.amjcard.2014.12.011","article-title":"Usefulness of retinal microvascular endothelial dysfunction as a predictor of coronary artery disease","volume":"115","author":"Al-Fiadh","year":"2015","journal-title":"Am J Cardiol"},{"key":"2026011721313575900_ejhf1537-bib-0012","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026011721313575900_ejhf1537-bib-0013","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1160\/TH11-11-0810","article-title":"Assessing vascular function using dynamic retinal diameter measurements: a new insight on the endothelium","volume":"107","author":"Heitmar","year":"2012","journal-title":"Thromb Haemost"},{"key":"2026011721313575900_ejhf1537-bib-0014","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1016\/S0161-6420(99)90525-0","article-title":"Methods for evaluation of retinal microvascular abnormalities associated with hypertension\/sclerosis in the Atherosclerosis Risk in Communities study","volume":"106","author":"Hubbard","year":"1999","journal-title":"Ophthalmology"},{"key":"2026011721313575900_ejhf1537-bib-0015","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1161\/CIRCULATIONAHA.112.093245","article-title":"The assessment of endothelial function: from research into clinical practice","volume":"126","author":"Flammer","year":"2012","journal-title":"Circulation"},{"key":"2026011721313575900_ejhf1537-bib-0016","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1161\/CIRCULATIONAHA.110.956490","article-title":"Acetaminophen increases blood pressure in patients with coronary artery disease","volume":"122","author":"Sudano","year":"2010","journal-title":"Circulation"},{"key":"2026011721313575900_ejhf1537-bib-0017","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1093\/eurheartj\/ehl254","article-title":"European Network for Non-Invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications","volume":"27","author":"Laurent","year":"2006","journal-title":"Eur Heart J"},{"key":"2026011721313575900_ejhf1537-bib-0018","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/1047322X.1990.10389587","article-title":"Estimation of average concentration in the presence of nondetectable values","volume":"5","author":"Hornung","year":"1990","journal-title":"Appl Occup Environ Hyg"},{"key":"2026011721313575900_ejhf1537-bib-0019","volume-title":"R: A Language and Environment for Statistical Computing. 3.4","author":"R Core Team","year":"2018","edition":"4th"},{"key":"2026011721313575900_ejhf1537-bib-0020","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1161\/CIRCULATIONAHA.109.886655","article-title":"Arterial stiffness and cardiovascular events: the Framingham Heart Study","volume":"121","author":"Mitchell","year":"2010","journal-title":"Circulation"},{"key":"2026011721313575900_ejhf1537-bib-0021","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.atherosclerosis.2013.12.044","article-title":"Retinal microvascular structure and function in patients with risk factors of atherosclerosis and coronary artery disease","volume":"233","author":"Al-Fiadh","year":"2014","journal-title":"Atherosclerosis"},{"key":"2026011721313575900_ejhf1537-bib-0022","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/rssb.12027","article-title":"Covariate balancing propensity score","volume":"76","author":"Imai","year":"2014","journal-title":"J R Stat Soc Series B Stat Methodol"},{"key":"2026011721313575900_ejhf1537-bib-0023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v009.i08","article-title":"Analysis of complex survey samples","volume":"9","author":"Lumley","year":"2004","journal-title":"Journal of Statistical Software"},{"key":"2026011721313575900_ejhf1537-bib-0024","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1111\/aos.12786","article-title":"Ageing effect on flicker-induced diameter changes in retinal microvessels of healthy individuals","volume":"94","author":"Seshadri","year":"2016","journal-title":"Acta Ophthalmol"},{"key":"2026011721313575900_ejhf1537-bib-0025","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/micc.12026","article-title":"Systemic associations of dynamic retinal vessel analysis: a review of current literature","volume":"20","author":"Lim","year":"2013","journal-title":"Microcirculation"},{"key":"2026011721313575900_ejhf1537-bib-0026","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejheart.2004.04.008","article-title":"Chronic heart failure is associated with vascular remodeling of the brachial artery","volume":"7","author":"Poelzl","year":"2005","journal-title":"Eur J Heart Fail"},{"key":"2026011721313575900_ejhf1537-bib-0027","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1076\/ceyr.21.6.944.6985","article-title":"Effect of shear stress on the hydraulic conductivity of cultured bovine retinal microvascular endothelial cell monolayers","volume":"21","author":"Lakshminarayanan","year":"2000","journal-title":"Curr Eye Res"},{"key":"2026011721313575900_ejhf1537-bib-0028","doi-asserted-by":"crossref","first-page":"14533","DOI":"10.1074\/jbc.R100011200","article-title":"Oxygen reduction by nitric-oxide synthases","volume":"276","author":"Stuehr","year":"2001","journal-title":"J Biol Chem"},{"key":"2026011721313575900_ejhf1537-bib-0029","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/j.jcin.2015.06.017","article-title":"Prevalence of coronary microvascular dysfunction among patients with chest pain and nonobstructive coronary artery disease","volume":"8","author":"Sara","year":"2015","journal-title":"JACC Cardiovasc Interv"},{"key":"2026011721313575900_ejhf1537-bib-0030","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1038\/jcbfm.2013.145","article-title":"Functional hyperemia and mechanisms of neurovascular coupling in the retinal vasculature","volume":"33","author":"Newman","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026011721313575900_ejhf1537-bib-0031","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1093\/eurheartj\/ehv132","article-title":"Cardiac endothelium-myocyte interaction: clinical opportunities for new heart failure therapies regardless of ejection fraction","volume":"36","author":"Lim","year":"2015","journal-title":"Eur Heart J"},{"key":"2026011721313575900_ejhf1537-bib-0032","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1042\/CS20130047","article-title":"The dependence of FMD% on baseline diameter: a problem solved by allometric scaling \u2013 no problem in this case","volume":"125","author":"DeVan","year":"2013","journal-title":"Clin Sci (Lond)"},{"key":"2026011721313575900_ejhf1537-bib-0033","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1007\/s00125-015-3639-z","article-title":"Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals","volume":"58","author":"Reimann","year":"2015","journal-title":"Diabetologia"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.1537","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.1537","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/8\/988\/66192729\/eurjhf_21_8_988.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/8\/988\/66192729\/eurjhf_21_8_988.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:32:06Z","timestamp":1768703526000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/21\/8\/988\/8407999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,4]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,7,4]]},"published-print":{"date-parts":[[2019,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.1537","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8]]},"published":{"date-parts":[[2019,7,4]]},"assertion":[{"value":"2019-01-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}