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 mm 3 [95% CI, 15.4–30.5]; mean volume in men 1399±425 mm 3 , in women 1011±242 mm 3 ). 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.

Sex-specific association between inflammation and endothelial function relevant gene and vulnerable carotid plaque

“…Sex differences have been recognized in the risk of carotid atherosclerotic plaque (Iemolo et al, 2004;Hellings et al, 2007;Ota et al, 2010;Vrijenhoek et al, 2013;Li et al, 2021). A recent prospective cohort study conducted in patients with recent ischemic cerebrovascular events and mild-to-moderate carotid stenosis also demonstrated that men are more likely to have a high-risk vulnerable carotid plaque with intraplaque hemorrhage and lipid-rich necrotic core than women, no matter the total plaque burden (van Dam-Nolen et al, 2022). Our findings provide a plausible genetic basis for the sex difference in carotid plaque vulnerability.…”

Regulation of cardiovascular calcification by lipids and lipoproteins

“…Several lines of evidence link cardiovascular calcification to hyperlipidemia. In a recent study of patients with cerebrovascular symptoms, hypercholesterolemia was associated significantly with carotid artery calcification, especially in male patients [4 ▪ ]. Among patients with heterozygous familial hypercholesterolemia, those with physical signs of tendon xanthomas and corneal arcus had both higher LDL levels and higher CAC score tertiles [5].…”

Sex Differences in Carotid Atherosclerosis: A Systematic Review and Meta-Analysis

“…Indeed, we recently found that specific combinations, such as the presence of calcifications, LRNC, and IPH, are more frequently seen in male patients. 49 This suggests that having a carotid plaque with multiple vulnerable plaque features could signify an even higher stroke risk and that new studies are needed to show whether these kind of plaques are indeed more prone to rupture.…”