Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis

Abstract

Background and purpose: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes.

Methods: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics.

Results: We found significant difference in total plaque volume between men and women (β=22.9 mm³ [95% CI, 15.4-30.5]; mean volume in men 1399±425 mm³, in women 1011±242 mm³). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3-6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2-4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2-7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1-5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2-8.6]).

Conclusions: In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01208025.

Keywords: atherosclerosis; carotid stenosis; computed tomography angiography; hemorrhage; lipid; magnetic resonance imaging; sex characteristics.

Figure 1.

Flowchart of patients included in the analyses. One hundred eighty-six patients have both magnetic resonance imaging (MRI) and multidetector-row computed tomographic angiography (MDCTA) of the carotid artery. PARISK indicates Plaque At RISK study.

Figure 2.

Forest plot of association between sex and plaque characteristics. Dependent variable is the presence of the plaque characteristics. Independent variable is sex with men as reference. Values are presented as odds ratio and 95% CIs. The model is adjusted for total plaque volume. IPH indicates intraplaque hemorrhage; LRNC, lipid-rich necrotic core; and TRFC, thin-or-ruptured fibrous cap.

Figure 3.

Forest plot of association between sex and plaque component volumes. Dependent variable is the volume of the plaque component. Independent variable is sex with men as reference. Values are presented as β and 95% CIs. Volumes of intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and calcifications are Ln transformed. The model is adjusted for total plaque volume.

Figure 4.

Forest plot of association between sex and combinations of plaque characteristics. Dependent variable is the presence of the combination of plaque characteristics. Independent variable is sex with men as reference. The model is adjusted for total plaque volume. IPH indicates intraplaque hemorrhage; LRNC, lipid-rich necrotic core; and TRFC, thin-or-ruptured fibrous cap.