Sex Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source

Abstract

Background We examined sex differences in nonstenotic carotid plaque composition in patients with embolic stroke of undetermined source (ESUS). Methods and Results Patients with anterior circulation ischemic stroke imaged with neck computed tomographic angiography who met criteria for ESUS or had atrial fibrillation were identified. Patients with atrial fibrillation were included as a negative control. Semiautomated plaque quantification software analyzed carotid artery bifurcations. Plaque subcomponent (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core) volumes were compared by sex and in paired analyses of plaque ipsilateral versus contralateral to stroke. Multivariate linear regressions tested for associations. Ninety-four patients with ESUS (55% women) and 95 patients with atrial fibrillation (47% women) were identified. Men with ESUS showed significantly higher volumes of calcified plaque (63.9 versus 19.6 mm³, P<0.001), IPH (9.4 versus 3.3 mm³, P=0.008) and a IPH/lipid rich necrotic core ratio (0.17 versus 0.07, P=0.03) in carotid plaque ipsilateral to stroke side than women. The atrial fibrillation cohort showed no significant sex differences in plaque volumes ipsilateral to stroke. Multivariate analyses of the ESUS cohort showed male sex was associated with IPH_ipsi (β=0.49; 95% CI, 0.11-0.87) and calcium_ipsi (β=0.78; 95% CI, 0.33-1.23). Paired plaque analyses in men with ESUS showed significantly higher calcified plaque (63.9 versus 34.1 mm³, P=0.03) and a trend of higher IPH_ipsi (9.4 versus 7.5 mm³, P=0.73) and lipid rich necrotic core_ipsi (59.0 versus 48.4 mm³, P=0.94) volumes. Conclusions Sex differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of nonstenosing carotid plaque as a stroke mechanism in men versus women.

Keywords: atherosclerosis; carotid artery; computed tomographic angiography; embolic stroke.

Figure 1. Plaque subcomponent volumes by sex.

A and B, Median volumes of each plaque subcomponent by sex for carotid plaque ipsilateral and contralateral to stroke side in the (A) ESUS and (B) AF cohorts are compared using Wilcoxon signed‐rank tests. Bar graphs represent medians with 95% CIs. Significant results are labeled with asterisks. *P<0.05; **P<0.001. C, Scatterplots show associations of plaque IPH_ipsi to LRNC_ipsi volumes by sex. Cubic B‐spline polynomial lines are fit to examine the differences in association between IPH and LRNC by sex. AF indicates atrial fibrillation; ESUS, embolic stroke of undetermined source; IPH, intraplaque hemorrhage; and LRNC, lipid rich necrotic core.