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In a validation cohort comprising 431 prospectively recruited ischemic stroke patients (mean age 59.1\u2009years; median follow-up 3.5\u2009years), men with plasma NOTCH3 (&amp;gt;1600\u2009pg\/ml) harbored increased risk of cardiovascular recurrence (adjusted hazards ratio 2.29, 95% CI 1.10\u20134.77); no significant association was observed in women. Chronic renal failure, peripheral artery disease and NT-pro-brain natriuretic peptide were significant predictors of plasma NOTCH3 in men without ischemic stroke (adjusted r2\u2009=\u20090.43). Following middle cerebral artery occlusion, NOTCH3 expression in mouse sera increased and peaked at 24\u2009h, persisting thereafter for at least 72\u2009h. In Apoe\u2212\/\u2212 atherosclerotic mice, NOTCH3 stained the endothelium of defective arterial lining and atherosclerotic plaques. Analysis of CECs isolated from stroke patients revealed increased gene expression of NOTCH3, further supporting endothelial damage underpinning NOTCH3-mediated atherosclerosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Findings from this study suggests that NOTCH3 could be important in cardiovascular recurrence following an ischemic stroke.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/qjmed\/hcae136","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T22:15:28Z","timestamp":1721081728000},"page":"846-857","source":"Crossref","is-referenced-by-count":4,"title":["Plasma NOTCH3 and the risk of cardiovascular recurrence in patients with ischemic stroke"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8946-3578","authenticated-orcid":false,"given":"R C 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Singapore,","place":["Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H Y","family":"Lim","sequence":"additional","affiliation":[{"name":"Immunology Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore,","place":["Singapore"]},{"name":"Immunology Programme, Life Sciences Institute, National University of Singapore , Singapore,","place":["Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore,","place":["Singapore"]},{"name":"Natural Products Research Center, Korea Institute of Science and Technology , Gangneung,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C L 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