Covert macrovascular disease and early outcome after ischemic cerebrovascular events

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.