Background Non-stenotic or non-territorial atherosclerotic plaques have long been considered clinically insignificant. However, emerging imaging evidence suggests that such covert macrovascular lesions may reflect systemic vascular vulnerability and influence neurological outcomes. This study investigated the prevalence and prognostic relevance of covert macrovascular disease (CMVD) in acute ischemic stroke.
Methods In a prospective single-center cohort, 714 consecutive patients with acute ischemic stroke or TIA (University Hospital Giessen, January–June 2023) underwent comprehensive neurovascular and cardiac imaging. CMVD was defined as atherosclerotic or structural vascular abnormalities outside the infarct-supplying territory or with <50 % luminal narrowing. The primary endpoint was functional independence at discharge (mRS 0–2). Multivariable logistic regression adjusted for age, sex, stroke subtype, NIHSS, and vascular risk factors.
Results CMVD was detected in 271 patients (37.9 %), most frequently as non-stenotic carotid plaques (27 %) or aortic arch atheroma ≥2 mm (9 %). CMVD was associated with higher age, hypertension (83 % vs. 70 %), prediabetes (40 % vs. 29 %), and central obesity (p < 0.05 each). Stroke severity was greater (NIHSS 8 vs. 6; p < 0.001), and favorable outcome less common (47 % vs. 63 %; p = 0.001). In adjusted analysis, CMVD independently predicted unfavorable outcome (aOR 1.82; 95 % CI 1.18–2.81; p = 0.006). Associations were strongest in cardioembolic stroke and ESUS subgroups.
Conclusion Covert macrovascular disease is common in ischemic stroke and independently linked to worse neurological outcomes. These lesions represent a hidden macrovascular burden connecting metabolic dysregulation with structural arterial injury. Integrating covert plaque assessment into vascular imaging may refine risk stratification and secondary prevention beyond the traditional “culprit lesion” paradigm.
