{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:08:05Z","timestamp":1773198485030,"version":"3.50.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Artif. Intell."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke is a heterogeneous disease influenced by inflammation, coagulation dysfunction, and metabolic disturbances. However, integrated analysis incorporating these biological domains for patient stratification remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective study of 132 ischemic stroke patients was conducted. Clinical, coagulation, inflammatory, and metabolic parameters were collected. Principal component analysis (PCA) was applied for dimensionality reduction and visualization.\n                      <jats:italic>K<\/jats:italic>\n                      -means clustering was then used to identify subtypes with the optimal cluster number validated by elbow plot and silhouette analysis. Differences among cluster\u2019s groups were assessed using ANOVA or Kruskal\u2013Wallis tests for continuous variables and Chi-square tests for categorical variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PCA revealed underlying heterogeneity among patients. Validated\n                      <jats:italic>K<\/jats:italic>\n                      -means clustering identified three distinct subtypes. Cluster 1 represented a low inflammatory subtype with reduced inflammatory markers. Cluster 2 was a high inflammatory and hypercoagulable subtype, characterized by elevated WBC, NEU, hsCRP, FIB, D-dimer, PT, INR along with a higher prevalence of coronary heart disease and carotid plaque, smoking, and drinking. Cluster 3 was a metabolic risk subtype, characterized by relatively younger age, elevated TG, CHOL, HDL-C, LDL-C, APOB, APOA-1 and APOB\/APOA1 ratio, and intermediate inflammatory activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Data driven clustering identified biologically distinct ischemic stroke subtypes based on inflammation, coagulation, and metabolic profiles. This stratification highlights the heterogeneity of ischemic stroke and may inform future personalized approaches to risk assessment and management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frai.2026.1776891","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T06:43:21Z","timestamp":1773125001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of ischemic stroke subtypes defined by inflammation, coagulation, and metabolic profiles"],"prefix":"10.3389","volume":"9","author":[{"given":"Hezhen","family":"Gao","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Clinical Laboratory, Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilraba","family":"Mahmut","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Clinical Laboratory, Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanshu","family":"Dai","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Clinical Laboratory, Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haimiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Clinical Laboratory, Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Clinical Laboratory, Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingya","family":"Huang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Clinical Laboratory, Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Clinical Laboratory, Huanhu Hospital Affiliated to Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1001\/archinte.162.22.2589","article-title":"Plasma measurement of D-dimer levels for the early diagnosis of ischemic stroke subtypes","volume":"162","author":"Ageno","year":"2002","journal-title":"Arch. Intern. Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa1910355","article-title":"A comparison of two LDL cholesterol targets after ischemic stroke","volume":"382","author":"Amarenco","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1136\/annrheumdis-2021-221763","article-title":"Osteoarthritis endotype discovery via clustering of biochemical marker data","volume":"81","author":"Angelini","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"110436","DOI":"10.1016\/j.compbiomed.2025.110436","article-title":"Optimizing clustering-based analytical methods with trimmed and sparse clustering","volume":"194","author":"Bernabe-Diaz","year":"2025","journal-title":"Comput. Biol. Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/s0140-6736(20)31179-x","article-title":"Stroke","volume":"396","author":"Campbell","year":"2020","journal-title":"Lancet"},{"key":"ref001","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3760\/cma.j.issn.1006-7876.2016.03.002","article-title":"Chinese guidelines for application of imaging in cerebral vascular diseases","volume":"49","year":"2016","journal-title":"Chin. J. Neurol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: a systematic analysis for the global burden of disease study 2019","volume":"20","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e154225","DOI":"10.1172\/JCI154225","article-title":"Neutrophil extracellular traps regulate ischemic stroke brain injury","volume":"132","author":"Denorme","year":"2022","journal-title":"J. Clin. Invest."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1161\/STROKEAHA.110.594945","article-title":"Inflammatory mechanisms of stroke","volume":"41","author":"Elkind","year":"2010","journal-title":"Stroke"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1056\/NEJMoa1107477","article-title":"C-reactive protein, fibrinogen, and cardiovascular disease prediction","volume":"367","author":"Kaptoge","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/nrneurol.2016.125","article-title":"Inflammatory risk factors, biomarkers and associated therapy in ischaemic stroke","volume":"12","author":"Esenwa","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/jth.15531","article-title":"Why fibrin biomechanical properties matter for hemostasis and thrombosis","volume":"20","author":"Feller","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1161\/STROKEAHA.115.011035","article-title":"Plasma D-dimer and incident ischemic stroke and coronary heart disease: the atherosclerosis risk in communities study","volume":"47","author":"Folsom","year":"2016","journal-title":"Stroke"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.atherosclerosis.2021.10.002","article-title":"Baseline or 90-day fibrinogen levels and long-term outcomes after ischemic stroke or TIA: results from the China national stroke registry III","volume":"337","author":"Hou","year":"2021","journal-title":"Atherosclerosis"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"108168","DOI":"10.1016\/j.jstrokecerebrovasdis.2024.108168","article-title":"Cross-sectional analysis of non-HDL\/HDL cholesterol ratio as a marker for cardiovascular disease risk in middle-aged and older adults: evidence from the CHARLS study","volume":"34","author":"Liu","year":"2025","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.4103\/NRR.NRR-D-24-01456","article-title":"Neuroinflammation strokes the brain: a double-edged sword in ischemic stroke","volume":"21","author":"Lombardozzi","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1161\/STROKEAHA.113.002289","article-title":"High-sensitivity C-reactive protein and interleukin-6-dominant inflammation and ischemic stroke risk: the northern Manhattan study","volume":"45","author":"Luna","year":"2014","journal-title":"Stroke"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1177\/2396987320984003","article-title":"Interleukin-6, C-reactive protein, fibrinogen, and risk of recurrence after ischaemic stroke: systematic review and meta-analysis","volume":"6","author":"Mccabe","year":"2021","journal-title":"Eur. Stroke J."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1177\/23969873241246489","article-title":"Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: an individual participant and summary-level data meta-analysis of 11 prospective studies","volume":"9","author":"Mccabe","year":"2024","journal-title":"Eur. Stroke J."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1161\/CIRCULATIONAHA.114.010637","article-title":"Phenomapping for novel classification of heart failure with preserved ejection fraction","volume":"131","author":"Shah","year":"2015","journal-title":"Circulation"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.jtha.2024.12.002","article-title":"Low thrombin inactivation capacity is associated with an increased risk of recurrent ischemic events after ischemic stroke at a young age","volume":"23","author":"Spiegelenberg","year":"2025","journal-title":"J. Thromb. Haemost."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s11011-016-9924-9","article-title":"Prognostic significance of major lipids in patients with acute ischemic stroke","volume":"32","author":"Tziomalos","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.08.007","article-title":"Endothelial function, inflammation, thrombosis, and basal ganglia perivascular spaces in patients with stroke","volume":"25","author":"Wang","year":"2016","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3892\/ijmm.2021.4854","article-title":"COVID-19 and ischemic stroke: mechanisms of hypercoagulability (review)","volume":"47","author":"Zhang","year":"2021","journal-title":"Int. J. Mol. Med."}],"container-title":["Frontiers in Artificial Intelligence"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frai.2026.1776891\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T06:43:23Z","timestamp":1773125003000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frai.2026.1776891\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":24,"alternative-id":["10.3389\/frai.2026.1776891"],"URL":"https:\/\/doi.org\/10.3389\/frai.2026.1776891","relation":{},"ISSN":["2624-8212"],"issn-type":[{"value":"2624-8212","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"article-number":"1776891"}}