{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:33:01Z","timestamp":1787157181021,"version":"build-2736575974"},"reference-count":43,"publisher":"JMIR Publications Inc.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMIR Med Inform"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec sec-type=\"background\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Screening for atherosclerosis is essential for early intervention, but conventional screening methods are often invasive and resource-intensive. As a result, there is growing interest in leveraging AI with noninvasive tools such as retinal fundus imaging to enable opportunistic cardiovascular risk assessment. The deep-learning funduscopic atherosclerosis score (DL-FAS) is an AI-derived biomarker, generated by a deep learning model, that was developed in a previous study to reflect the likelihood of carotid artery atherosclerosis from retinal fundus images.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"objective\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to externally validate DL-FAS in a multicenter health checkup population and investigate its association with coronary artery calcification to gain deeper insights into its ability to reflect the broader systemic atherosclerotic burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from 108,982 participants in a Korean health checkup population who underwent retinal fundus imaging and at least one of either carotid artery sonography or coronary artery calcium scoring across 5 health-promotion centers operated by the Korea Association of Health Promotion between 2018 and 2021. Carotid atherosclerosis was defined by increased intima-media thickness (\u2265\n0.9 mm), atheroma, or stenosis. A coronary artery calcium score &gt;0 indicated the presence of coronary artery calcification. DL-FAS (range 0\u20101) was generated for each fundus image, and the average score from both eyes was used as the final DL-FAS when available. The discriminative performance of DL-FAS for carotid atherosclerosis was assessed using the area under the receiver operating characteristic curve. We performed multivariable logistic regression, adjusted for the Pooled Cohort Equations (PCE) 10-year cardiovascular risk score, to quantify the associations between DL-FAS and both outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The area under the receiver operating characteristic curve for detecting carotid atherosclerosis was 0.700 (95% CI 0.697\u20100.703), confirming the generalizability of DL-FAS across multiple centers. In multivariable logistic regression adjusted for the PCE score, a 10% absolute increase in DL-FAS was associated with both carotid atherosclerosis (odds ratio 1.29, 95% CI 1.28\u20101.31) and coronary artery calcification (odds ratio 1.29, 95% CI 1.24\u20101.33). These associations remained significant among participants aged &lt;60 years, as well as within the PCE-defined low- and moderate-risk subgroups, highlighting the potential utility of DL-FAS in populations that may benefit most from early detection and intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DL-FAS was externally validated in a large, multicenter health checkup dataset and was significantly associated with both carotid atherosclerosis and coronary artery calcification. These findings highlight its potential as a noninvasive biomarker associated with systemic atherosclerotic burden and cardiovascular risk stratification, particularly in the context of opportunistic screening.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2196\/77335","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:22:52Z","timestamp":1787156572000},"page":"e77335-e77335","source":"Crossref","is-referenced-by-count":0,"title":["Multicenter External Validation of an AI-Based Funduscopic Carotid Atherosclerosis Score and Assessment of Its Association With Coronary Artery Calcification: External Validation Study"],"prefix":"10.2196","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-5465","authenticated-orcid":false,"given":"Changho","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8586-0645","authenticated-orcid":false,"given":"Jooyoung","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7942-1286","authenticated-orcid":false,"given":"Jaewon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4547-0861","authenticated-orcid":false,"given":"Hyeokjong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9954-6422","authenticated-orcid":false,"given":"Kyae Hyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-5897","authenticated-orcid":false,"given":"Seon","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8049-1873","authenticated-orcid":false,"given":"Heesung","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0512-1189","authenticated-orcid":false,"given":"Suyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7498-4829","authenticated-orcid":false,"given":"Sang Min","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1010","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"issue":"10053","key":"R1","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/S0140-6736(16)31012-1","article-title":"Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"GBD 2015 Mortality and Causes of Death Collaborators","journal-title":"Lancet"},{"issue":"1","key":"R2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacc.2017.04.052","article-title":"Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015","volume":"70","author":"Roth","journal-title":"JACC"},{"issue":"4","key":"R3","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1161\/CIRCRESAHA.115.306247","article-title":"Imaging atherosclerosis","volume":"118","author":"Tarkin","journal-title":"Circ Res"},{"issue":"1","key":"R4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1161\/ATVBAHA.123.319932","article-title":"Subclinical atherosclerosis collaborative. subclinical atherosclerosis: part 1: what is it? Can it be defined at the histological level?","volume":"44","author":"Kawai","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"4","key":"R5","doi-asserted-by":"publisher","first-page":"e192","DOI":"10.1016\/S2589-7500(20)30025-X","article-title":"Automated CT biomarkers for opportunistic prediction of future cardiovascular events and mortality in an asymptomatic screening population: a retrospective cohort study","volume":"2","author":"Pickhardt","journal-title":"Lancet Digit Health"},{"issue":"3","key":"R6","doi-asserted-by":"publisher","DOI":"10.1056\/aioa2400948","article-title":"Opportunistic screening of chronic liver disease with deep-learning\u2013enhanced echocardiography","volume":"2","author":"Sahashi","journal-title":"NEJM AI"},{"issue":"17","key":"R7","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1093\/eurheartj\/eht023","article-title":"The eye and the heart","volume":"34","author":"Flammer","journal-title":"Eur Heart J"},{"issue":"3","key":"R8","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/s1474-4422(04)00682-9","article-title":"Is retinal photography useful in the measurement of stroke risk?","volume":"3","author":"Wong","journal-title":"Lancet Neurol"},{"issue":"22","key":"R9","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1056\/NEJMra032865","article-title":"Hypertensive retinopathy","volume":"351","author":"Wong","journal-title":"N Engl J Med"},{"issue":"3","key":"R10","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41551-018-0195-0","article-title":"Prediction of cardiovascular risk factors from retinal fundus photographs via deep learning","volume":"2","author":"Poplin","journal-title":"Nat Biomed Eng"},{"issue":"10","key":"R11","doi-asserted-by":"publisher","first-page":"e526","DOI":"10.1016\/S2589-7500(20)30216-8","article-title":"Prediction of systemic biomarkers from retinal photographs: development and validation of deep-learning algorithms","volume":"2","author":"Rim","journal-title":"Lancet Digit Health"},{"issue":"1","key":"R12","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-025-01957-9","article-title":"Optimizing retinal images based carotid atherosclerosis prediction with explainable foundation models","volume":"8","author":"Lee","journal-title":"NPJ Digit Med"},{"issue":"6","key":"R13","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1093\/ehjdh\/ztae068","article-title":"Prediction of cardiovascular markers and diseases using retinal fundus images and deep learning: a systematic scoping review","volume":"5","author":"Li","journal-title":"Eur Heart J Digit Health"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2020.03.027","article-title":"Association of cardiovascular mortality and deep learning-funduscopic atherosclerosis score derived from retinal fundus images","volume":"217","author":"Chang","journal-title":"Am J Ophthalmol"},{"issue":"1","key":"R15","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1056\/NEJM199901073400103","article-title":"Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults","volume":"340","author":"O\u2019Leary","journal-title":"N Engl J Med"},{"issue":"34","key":"R16","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","journal-title":"Eur Heart J"},{"issue":"7","key":"R17","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.jcmg.2012.03.013","article-title":"Carotid plaque burden as a measure of subclinical atherosclerosis: comparison with other tests for subclinical arterial disease in the High Risk Plaque BioImage study","volume":"5","author":"Sillesen","journal-title":"JACC Cardiovasc Imaging"},{"issue":"2","key":"R18","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.atherosclerosis.2012.11.008","article-title":"Coronary and carotid atherosclerosis: similarities and differences","volume":"227","author":"Jashari","journal-title":"Atherosclerosis"},{"issue":"13","key":"R19","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1056\/NEJMoa072100","article-title":"Coronary calcium as a predictor of coronary events in four racial or ethnic groups","volume":"358","author":"Detrano","journal-title":"N Engl J Med"},{"issue":"3","key":"R20","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1161\/CIRCULATIONAHA.123.065657","article-title":"Coronary artery calcification: current concepts and clinical implications","volume":"149","author":"Onnis","journal-title":"Circulation"},{"key":"R21","doi-asserted-by":"crossref","unstructured":"Chollet F . Xception: deep learning with depthwise separable convolutions. Presented at: 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR); Jul 21-26, 2017:1800-1807; Honolulu, HI. [doi: 10.1109\/CVPR.2017.195]","DOI":"10.1109\/CVPR.2017.195"},{"issue":"3","key":"R22","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s11263-015-0816-y","article-title":"ImageNet large scale visual recognition challenge","volume":"115","author":"Russakovsky","journal-title":"Int J Comput Vis"},{"issue":"25 Suppl 2","key":"R23","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1161\/01.cir.0000437741.48606.98","article-title":"2013 ACC\/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"Goff","journal-title":"Circulation"},{"issue":"25","key":"R24","doi-asserted-by":"publisher","first-page":"e1082","DOI":"10.1161\/CIR.0000000000000625","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"139","author":"Grundy","journal-title":"Circulation"},{"issue":"5","key":"R25","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-005025","article-title":"A coronary heart disease prediction model: the Korean Heart Study","volume":"4","author":"Jee","journal-title":"BMJ Open"},{"issue":"3","key":"R26","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","volume":"44","author":"DeLong","journal-title":"Biometrics"},{"issue":"3","key":"R27","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1056\/NEJMoa1012592","article-title":"Carotid-wall intima-media thickness and cardiovascular events","volume":"365","author":"Polak","journal-title":"N Engl J Med"},{"issue":"4","key":"R28","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1161\/CIRCULATIONAHA.106.628875","article-title":"Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis","volume":"115","author":"Lorenz","journal-title":"Circulation"},{"issue":"8","key":"R29","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1161\/CIRCULATIONAHA.122.061193","article-title":"Insurance payers should cover selective coronary artery calcium testing in intermediate risk primary prevention patients","volume":"146","author":"Greenland","journal-title":"Circulation"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmedr.2019.100879","article-title":"Coronary artery calcium testing: a call for universal coverage","volume":"15","author":"Naghavi","journal-title":"Prev Med Rep"},{"issue":"4","key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajoint.2025.100194","article-title":"A comprehensive review of portable retinal cameras: technical features, AI integration, and clinical potential","volume":"2","author":"Nakayama","journal-title":"AJO Int"},{"issue":"5","key":"R32","doi-asserted-by":"publisher","DOI":"10.15829\/1560-4071-2020-3826","article-title":"2019 ESC\/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk [Article in Russian]","volume":"25","author":"Mach","journal-title":"Russ J Cardiol"},{"issue":"6","key":"R33","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1161\/01.atv.20.6.1644","article-title":"Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study","volume":"20","author":"Klein","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"R34","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/j.amjcard.2005.05.070","article-title":"Relation of atherosclerotic changes in retinal arteries to the extent of coronary artery disease","volume":"96","author":"Tedeschi-Reiner","journal-title":"Am J Cardiol"},{"issue":"3","key":"R35","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s00380-012-0258-1","article-title":"The predictive value of retinal vascular findings for carotid artery atherosclerosis: are further recommendations with regard to carotid atherosclerosis screening needed?","volume":"28","author":"Song","journal-title":"Heart Vessels"},{"issue":"4","key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2009.05.030","article-title":"The relationship between retinal microvascular abnormalities and coronary heart disease: a review","volume":"123","author":"McClintic","journal-title":"Am J Med"},{"issue":"5","key":"R37","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/S0161-6420(03)00084-8","article-title":"Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study","volume":"110","author":"Wong","journal-title":"Ophthalmology"},{"issue":"9","key":"R38","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1001\/jama.287.9.1153","article-title":"Retinal arteriolar narrowing and risk of coronary heart disease in men and women","volume":"287","author":"Wong","journal-title":"JAMA"},{"issue":"11","key":"R39","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1136\/hrt.2006.090522","article-title":"Retinal vascular calibre and the risk of coronary heart disease-related death","volume":"92","author":"Wang","journal-title":"Heart"},{"issue":"18","key":"R40","doi-asserted-by":"publisher","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","journal-title":"Circulation"},{"issue":"6","key":"R41","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1167\/iovs.05-1539","article-title":"Retinal vascular caliber, cardiovascular risk factors, and inflammation: the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"47","author":"Wong","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"R42","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1161\/01.HYP.0000216717.72048.6c","article-title":"Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke","volume":"47","author":"Witt","journal-title":"Hypertension"},{"issue":"1","key":"R43","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41551-019-0487-z","article-title":"Detection of anaemia from retinal fundus images via deep learning","volume":"4","author":"Mitani","journal-title":"Nat Biomed Eng"}],"container-title":["JMIR Medical Informatics"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:22:53Z","timestamp":1787156573000},"score":1,"resource":{"primary":{"URL":"https:\/\/medinform.jmir.org\/2026\/1\/e77335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":43,"URL":"https:\/\/doi.org\/10.2196\/77335","relation":{},"ISSN":["2291-9694"],"issn-type":[{"value":"2291-9694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"article-number":"v14i10053e77335"}}