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Whether non-culprit macrovascular abnormalities below conventional stenosis thresholds represent a clinically relevant form of vascular vulnerability remains unclear. We investigated the prevalence and prognostic significance of covert macrovascular disease (CMVD) in acute ischemic stroke and transient ischemic attack (TIA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective observational cohort, consecutive patients admitted with ischemic stroke or TIA underwent standardized vascular imaging. CMVD was defined as non-culprit macrovascular pathology not meeting TOAST criteria for large-artery atherosclerosis, including non-stenotic carotid or vertebral plaques (&lt;\u200950%), plaques outside the infarct-supplying territory, aortic arch atheroma (\u2265\u20092 mm), or non-hemodynamically relevant vascular elongation or kinking. Lesions were adjudicated by blinded experts. The primary outcome was favorable functional status at discharge (modified Rankin Scale [mRS] 0\u20132). Multivariable logistic regression adjusted for demographic, clinical, and vascular risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 714 patients (mean age 72\u2009\u00b1\u20099\u00a0years; 43% women), CMVD was present in 271 (37.9%; 95% CI, 34.4\u201341.6). CMVD prevalence varied by stroke etiology, highest in large-artery atherosclerosis (56%) and cardioembolic stroke (41%), intermediate in ESUS (35%), and lowest in small-vessel occlusion (21%). Patients with CMVD had higher admission stroke severity and lower rates of favorable functional outcome at discharge (47.1% vs. 63.2%; p\u2009=\u20090.001), as well as higher in-hospital mortality (6.3% vs. 2.7%; p\u2009=\u20090.049). CMVD remained independently associated with unfavorable outcome (adjusted OR 1.82; 95% CI, 1.18\u20132.81; p\u2009=\u20090.006) and an increased risk of recurrent ischemic stroke during follow-up (HR, 1.84; 95% CI, 1.05\u20133.20).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Covert macrovascular disease is common in acute ischemic cerebrovascular events and independently predicts worse early functional outcome. These findings support CMVD as a clinically meaningful marker of systemic vascular vulnerability beyond culprit stenosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00392-026-02947-x","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:03:37Z","timestamp":1780916617000},"page":"1410-1423","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Covert macrovascular disease and early outcome after ischemic cerebrovascular events"],"prefix":"10.1007","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0534-132X","authenticated-orcid":false,"given":"Priyanka","family":"Boettger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Vollmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamschid","family":"Sedighi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz Frederik","family":"Noll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buerke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun","family":"Kraemer-Best","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Juenemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar Alhaj","family":"Omar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Sossalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"issue":"11","key":"2947_CR1","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1001\/jamaneurol.2023.3344","volume":"80","author":"PC Lavall\u00e9e","year":"2023","unstructured":"Lavall\u00e9e PC et al (2023) Underlying causes of TIA and minor ischemic stroke and risk of major vascular events. 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