Cervical Internal Carotid Artery Plaque Composition and Chronic White Matter Disease in Patients with Noncardioembolic Stroke: A Multicenter Analysis.

BACKGROUND: Cerebral white matter disease (WMD) may result from the accumulation of silent embolic brain infarcts in the setting of subclinical, nonstenotic cervical carotid atherosclerosis. The contribution of cervical plaque to the burden of WMD is not well established. METHODS: A multicenter, retrospective cohort of consecutive adult patients with stroke due to cervical carotid atherostenosis (>50% luminal stenosis), small vessel disease, or cryptogenic mechanism with unilateral hemispheric stroke was queried. Maximum cervical carotid plaque thickness was used to predict higher grade WMD (Fazekas grade 2-3 versus 0-1) in unadjusted logistic regression, stratified by quartile of interside plaque (mean total plaque in axial dimension of the left and right cervical carotid arteries), and adjusted for age, stroke mechanism, atherosclerotic risk factors, and clustering by site. RESULTS: Of the 375 included patients, the median age was 66 years (interquartile range 58-74), 170 (45.3%) were female, and the median interside cervical internal carotid artery plaque thickness was 1.8 mm (interquartile range 0.2-3.2). Compared with patients in the lowest quartile of interside plaque (<0.2 mm), those in higher quartiles had higher grade WMD (Q3 adjusted odds ratio [aOR] 1.44, 95% CI, 1.09-1.89; Q4 aOR 1.85, 95% CI, 1.37-2.50). The association with higher grade WMD persisted in a sensitivity analysis considering interside plaque thickness as a continuous variable (adjusted incidence rate ratio/1 mm plaque 1.09, 95% CI, 1.02-1.17). The effect was preserved across stroke mechanisms, sex, and infarct pattern (cortical versus subcortical); however, younger patients had a stronger association between plaque thickness and WMD, whereas the eldest patients had no association (P interaction <0.01). CONCLUSIONS: In this cohort of patients with noncardioembolic stroke, greater interside cervical carotid plaque thickness was strongly associated with greater WMD. This association supports a potential role of subclinical cervical carotid artery atherosclerosis as a contributor to WMD, which may represent the accumulation of silent brain infarcts.