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Updated: Jun 9, 2026

Transient Middle Cerebral Artery Occlusion Model of Stroke
Published on: August 11, 2023
Covert macrovascular disease and early outcome after ischemic cerebrovascular events
Priyanka Boettger1,2, Linda Vollmann3, Jamschid Sedighi3,4
1Department of Cardiology, Angiology and Critical Care Medicine, Justus Liebig University, Klinikstrasse, 33 35392, Giessen, Germany. priyanka.boettger@uni-giessen.de.
Background:
Covert cerebrovascular disease is traditionally defined as microvascular brain injury. 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).
Methods:
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 (< 50%), plaques outside the infarct-supplying territory, aortic arch atheroma (≥ 2 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] 0-2). Multivariable logistic regression adjusted for demographic, clinical, and vascular risk factors.
Results:
Among 714 patients (mean age 72 ± 9 years; 43% women), CMVD was present in 271 (37.9%; 95% CI, 34.4-41.6). 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 = 0.001), as well as higher in-hospital mortality (6.3% vs. 2.7%; p = 0.049). CMVD remained independently associated with unfavorable outcome (adjusted OR 1.82; 95% CI, 1.18-2.81; p = 0.006) and an increased risk of recurrent ischemic stroke during follow-up (HR, 1.84; 95% CI, 1.05-3.20).
Conclusions:
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.
Insights
Covert macrovascular disease (CMVD) is common in stroke patients and predicts worse outcomes. Identifying CMVD is crucial for understanding systemic vascular vulnerability beyond significant stenosis.
Area of Science:
- Neurology
- Vascular Medicine
- Cardiovascular Research
Background:
- Traditionally, covert cerebrovascular disease focuses on microvascular injury.
- The clinical relevance of macrovascular abnormalities below stenosis thresholds is uncertain.
- This study investigates covert macrovascular disease (CMVD) in acute ischemic stroke and TIA.
Purpose of the Study:
- To determine the prevalence of CMVD in patients with acute ischemic stroke or TIA.
- To assess the prognostic significance of CMVD on early functional outcomes.
- To evaluate CMVD as a marker of systemic vascular vulnerability.
Main Methods:
- Prospective observational cohort study of 714 patients with ischemic stroke or TIA.
- Standardized vascular imaging used to define CMVD (non-stenotic plaques, aortic atheroma, vascular kinking).
- Multivariable logistic regression analyzed associations with functional status (mRS 0-2) and mortality.
Main Results:
- CMVD was present in 37.9% of patients.
- Patients with CMVD had higher stroke severity, lower favorable outcomes (47.1% vs. 63.2%), and increased in-hospital mortality (6.3% vs. 2.7%).
- CMVD independently predicted unfavorable outcomes (aOR 1.82) and recurrent ischemic stroke (HR 1.84).
Conclusions:
- Covert macrovascular disease is a prevalent finding in acute cerebrovascular events.
- CMVD is an independent predictor of worse early functional outcomes.
- CMVD serves as a clinically significant indicator of systemic vascular vulnerability.
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