Abstract 2024: Gender Associated Differences In Plaque Phenotype Of Patients With Hemodynamically Significant Carotid Stenosis
Background Women with hemodynamically significant carotid artery stenosis have a smaller risk of stroke than men. We hypothesize that this gender difference may be based on a different composition of the carotid artery plaque.
Methods Carotid endarterectomy specimens obtained from 135 women and 315 men undergoing CEA (April 2002 - November 2005) were characterized by immunohistochemistry (overall phenotype - HE, macrophages - CD68, smooth muscle cells - alpha-actin, collagen - picrosirius red, calcifications - HE), and interleukin −6, −8 and matrix metalloproteinase (MMP) −8, −9 activity measurements. Clinical presentation and cardiovascular risk factors were recorded from patient charts and questionnaires.
Results Atheromatous plaques (>40% fat) were less frequently observed in women compared to men (22% vs. 40%; p<0.001). In addition, plaques obtained from female patients more frequently revealed low macrophage staining (11% vs. 18%; p=0.05) and strong smooth muscle cell staining (38% vs. 24%; p=0.001). Compared to men, women had lower plaque concentration of IL-8 (p=0.001) and lower MMP-8 (p=0.01) and MMP-9 (p=0.07) activity. The observed differences were most pronounced in asymptomatic women who showed the most stable plaques, with an atheromatous plaque in only 9% of cases, compared to 39% in asymptomatic men. (p=0.02). In addition, a large proportion of plaques obtained from asymptomatic females showed high smooth muscle cell content (53% vs. 30%; p=0.03) and high collagen content (55% vs. 24%; p=0.003). All relations between gender and plaque characteristics, except for MMP-8, remained intact in a multivariate analysis including clinical presentation and other cardiovascular risk factors.
Conclusions Women operated on for carotid artery stenosis have more stable, less inflammatory plaques compared to men, independent of clinical presentation and cardiovascular risk profile. This observation could explain why women with hemodynamically significant carotid artery stenosis have a lower risk of stroke than men and thus benefit less from carotid endarterectomy.