Covert macrovascular disease and early outcome after ischemic cerebrovascular events

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).

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.

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).

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.