{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:16:00Z","timestamp":1783098960414,"version":"3.54.6"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Klinikum Rechts der Isar of the Technical University of Munich"},{"name":"Else-Kr\u00f6ner-Fresenius Foundation","award":["P27\/10\/\/A33\/10"],"award-info":[{"award-number":["P27\/10\/\/A33\/10"]}]},{"name":"Servier Research Grant in Hypertension","award":["111014\/ASD\/StgDM"],"award-info":[{"award-number":["111014\/ASD\/StgDM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We adopted a workflow consisting of noise reduction and extraction of independent components within DVA signals. Predictor performance was assessed in survival random forest models. Applying our technique to the prediction of all-cause mortality in a cohort of 214 haemodialysis patients resulted in the selection of a component which was highly correlated to maximal venous dilation following flicker stimulation (vMax), a previously identified predictor, confirming the validity of our approach. When fitting for CV mortality as the outcome of interest, a combination of three components derived from the arterial signal resulted in a marked improvement in predictive performance. Clustering analysis suggested that these independent components identified groups of patients with substantially higher CV mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results provide a machine learning workflow to improve the predictive performance of DVA and identify groups of haemodialysis patients at high risk of CV mortality. Our approach may also prove to be promising for DVA signal analysis in other CV disease states.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvab040","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T03:47:04Z","timestamp":1612928824000},"page":"612-621","source":"Crossref","is-referenced-by-count":13,"title":["Identification of cardiovascular high-risk groups from dynamic retinal vessel signals using untargeted machine learning"],"prefix":"10.1093","volume":"118","author":[{"given":"Stanislas","family":"Werfel","sequence":"first","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, Technical University Munich, Ismaninger Stra\u00dfe 22, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"G\u00fcnthner","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, Technical University Munich, Ismaninger Stra\u00dfe 22, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6765-6352","authenticated-orcid":false,"given":"Alexander","family":"Hapfelmeier","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Statistics and Epidemiology, School of Medicine, Technical University Munich, Munich, Germany"},{"name":"Institute of General Practice and Health Services Research, School of Medicine, Technical University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-4205","authenticated-orcid":false,"given":"Henner","family":"Hanssen","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine, Institute of Exercise and Health Sciences (ISSW), University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-957X","authenticated-orcid":false,"given":"Konstantin","family":"Kotliar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Technomathematics, Aachen University of Applied Sciences, Juelich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Heemann","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, Technical University Munich, Ismaninger Stra\u00dfe 22, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-2190","authenticated-orcid":false,"given":"Christoph","family":"Schmaderer","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Klinikum Rechts der Isar, Technical University Munich, Ismaninger Stra\u00dfe 22, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"2022013117270021100_cvab040-B1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/j.1755-3768.2009.01587.x","article-title":"Use of the retinal vessel analyzer in ocular blood flow research","volume":"88","author":"Garhofer","year":"2010","journal-title":"Acta Ophthalmol"},{"key":"2022013117270021100_cvab040-B2","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":"2022013117270021100_cvab040-B3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mvr.2010.11.007","article-title":"Dynamic retinal vessel response to flicker in obesity: a methodological approach","volume":"81","author":"Kotliar","year":"2011","journal-title":"Microvasc Res"},{"key":"2022013117270021100_cvab040-B4","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":"S\u00f6rensen","year":"2016","journal-title":"Circulation"},{"key":"2022013117270021100_cvab040-B5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/eurheartj\/ehx565","article-title":"Retinal microvascular dysfunction in heart failure","volume":"39","author":"N\u00e4gele","year":"2018","journal-title":"Eur Heart J"},{"key":"2022013117270021100_cvab040-B6","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1002\/ejhf.1537","article-title":"Retinal microvascular dysfunction in patients with coronary artery disease with and without heart failure: a continuum?","volume":"21","author":"Barthelmes","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"2022013117270021100_cvab040-B7","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1161\/CIRCRESAHA.118.314318","article-title":"Impaired retinal vessel dilation predicts mortality in end-stage renal disease","volume":"124","author":"G\u00fcnthner","year":"2019","journal-title":"Circ Res"},{"key":"2022013117270021100_cvab040-B8","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/sms.13560","article-title":"Retinal endothelial function in cardiovascular risk patients: a randomized controlled exercise trial","volume":"30","author":"Streese","year":"2020","journal-title":"Scand J Med Sci Sports"},{"key":"2022013117270021100_cvab040-B9","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":"2022013117270021100_cvab040-B10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/jemt.23172","article-title":"Automated techniques for blood vessels segmentation through fundus retinal images: a review","volume":"82","author":"Akbar","year":"2019","journal-title":"Microsc Res Tech"},{"key":"2022013117270021100_cvab040-B11","first-page":"880","author":"Fathalla","year":"2017"},{"key":"2022013117270021100_cvab040-B12","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.procs.2018.07.292","article-title":"Partially lazy classification of cardiovascular risk via multi-way graph cut optimization","volume":"126","author":"Fathalla","year":"2018","journal-title":"Procedia Comput Sci"},{"key":"2022013117270021100_cvab040-B13","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.kint.2017.11.020","article-title":"Declining comorbidity-adjusted mortality rates in English patients receiving maintenance renal replacement therapy","volume":"93","author":"Storey","year":"2018","journal-title":"Kidney Int"},{"key":"2022013117270021100_cvab040-B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12882-016-0374-8","article-title":"Rationale and study design of the prospective, longitudinal, observational cohort study \u201crISk strAtification in end-stage renal disease\u201d (ISAR) study","volume":"17","author":"Schmaderer","year":"2016","journal-title":"BMC Nephrol"},{"key":"2022013117270021100_cvab040-B15","doi-asserted-by":"crossref","first-page":"12906","DOI":"10.1038\/s41598-017-13349-5","article-title":"Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer\u2019s disease","volume":"7","author":"Kotliar","year":"2017","journal-title":"Sci Rep"},{"key":"2022013117270021100_cvab040-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/1970392.1970395","article-title":"Robust principal component analysis?","volume":"58","author":"Cand\u00e8s","year":"2011","journal-title":"J ACM"},{"key":"2022013117270021100_cvab040-B17","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0893-6080(00)00026-5","article-title":"Independent component analysis: algorithms and applications","volume":"13","author":"Hyv\u00e4rinen","year":"2000","journal-title":"Neural Netw"},{"key":"2022013117270021100_cvab040-B18","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1214\/08-AOAS169","article-title":"Random survival forests","volume":"2","author":"Ishwaran","year":"2008","journal-title":"Ann Appl Stat"},{"key":"2022013117270021100_cvab040-B19","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/biostatistics\/kxu010","article-title":"Random survival forests for competing risks","volume":"15","author":"Ishwaran","year":"2014","journal-title":"Biostatistics"},{"key":"2022013117270021100_cvab040-B20","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/biostatistics\/kxt059","article-title":"Concordance for prognostic models with competing risks","volume":"15","author":"Wolbers","year":"2014","journal-title":"Biostatistics"},{"key":"2022013117270021100_cvab040-B21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/ki.2009.413","article-title":"An improved comorbidity index for outcome analyses among dialysis patients","volume":"77","author":"Liu","year":"2010","journal-title":"Kidney Int"},{"key":"2022013117270021100_cvab040-B22","first-page":"4765","article-title":"A unified approach to interpreting model predictions","volume":"pp.","author":"Lundberg","year":"2017"},{"key":"2022013117270021100_cvab040-B23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v061.i06","article-title":"NbClust: an R package for determining the relevant number of clusters in a data set","volume":"61","author":"Charrad","year":"2014","journal-title":"J Stat Softw"},{"key":"2022013117270021100_cvab040-B24","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.tig.2018.07.003","article-title":"Enter the matrix: factorization uncovers knowledge from omics","volume":"34","author":"Stein-O\u2019Brien","year":"2018","journal-title":"Trends Genet"},{"key":"2022013117270021100_cvab040-B25","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1016\/j.cell.2016.11.048","article-title":"A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response","volume":"167","author":"Adamson","year":"2016","journal-title":"Cell"},{"key":"2022013117270021100_cvab040-B26","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1161\/01.HYP.0000090122.38230.41","article-title":"Hypertensive retinal vessel wall signs in a general older population: the Blue Mountains Eye Study","volume":"42","author":"Wang","year":"2003","journal-title":"Hypertension"},{"key":"2022013117270021100_cvab040-B27","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1161\/CIRCULATIONAHA.116.023425","article-title":"Retinal vessel calibers in predicting long-term cardiovascular outcomes: the atherosclerosis risk in communities study","volume":"134","author":"Seidelmann","year":"2016","journal-title":"Circulation"},{"key":"2022013117270021100_cvab040-B28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s42256-019-0138-9","article-title":"From local explanations to global understanding with explainable AI for trees","volume":"2","author":"Lundberg","year":"2020","journal-title":"Nat Mach Intell"},{"key":"2022013117270021100_cvab040-B29","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1053\/j.ajkd.2006.12.012","article-title":"diuretic use, residual renal function, and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Pattern Study (DOPPS)","volume":"49","author":"Bragg-Gresham","year":"2007","journal-title":"Am J Kidney Dis"},{"key":"2022013117270021100_cvab040-B30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2215\/CJN.05080418","article-title":"Association of continuation of loop diuretics at hemodialysis initiation with clinical outcomes","volume":"14","author":"Sibbel","year":"2019","journal-title":"CJASN"},{"key":"2022013117270021100_cvab040-B31","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1214\/aos\/1176350951","article-title":"A class of K-sample tests for comparing the cumulative incidence of a competing risk","volume":"16","author":"Gray","year":"1988","journal-title":"Ann Stat"},{"key":"2022013117270021100_cvab040-B32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ijcard.2016.04.151","article-title":"Development and validation of cardiovascular risk scores for haemodialysis patients","volume":"216","author":"Anker","year":"2016","journal-title":"Int J Cardiol"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvab040\/36349031\/cvab040.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/118\/2\/612\/42340655\/cvab040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/118\/2\/612\/42340655\/cvab040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T17:40:43Z","timestamp":1643650843000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/118\/2\/612\/6133256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,12]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,12]]},"published-print":{"date-parts":[[2022,1,29]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvab040","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2,1]]},"published":{"date-parts":[[2021,2,12]]}}}