Background and aims: The sex- and age-related differences in the composition of iliofemoral atherosclerotic plaques are largely unknown. Therefore, the aim of the current study is to gain insight into plaque composition across strata of age and sex in a large cohort of vascular surgery patients. Methods: Peripheral atherosclerotic plaques of patients who underwent iliofemoral endarterectomy (n = 790) were harvested between 2002 and 2014. The plaques were semi-quantitatively analyzed for the presence of lipid cores, calcifications, plaque hemorrhages (PH), collagen, macrophage and smooth muscle cell (SMC) content, and quantitatively for microvessel density. Patients were stratified by age tertiles and sex. Results: Ageing was independently associated with rupture-prone iliofemoral plaque characteristics, such as higher prevalence of plaque calcifications (OR 1.52 (95%CI:1.03–2.24) p = 0.035) and PH (OR 1.46 (95%CI:1.01–2.09) p = 0.042), and lower prevalence of collagen (OR 0.52 (95%CI:0.31–0.86) p = 0.012) and SMCs (OR 0.59 (95%CI:0.39–0.90) p = 0.015). Sex-stratified data showed that men had a higher prevalence of lipid cores (OR 1.62 (95%CI:1.06–2.45) p = 0.025) and PH (OR 1.62 (95%CI:1.16–2.54) p = 0.004) compared to women. These sex-differences attenuated with increasing age, with women showing an age-related increase in calcifications (p = 0.002), PH (p = 0.015) and decrease in macrophages (p = 0.005). In contrast, men only showed a decrease in collagen (p = 0.043). Conclusions: Atherosclerotic iliofemoral plaques derived from men display more rupture-prone characteristics compared to women. Yet, this difference is attenuated with an increase in age, with older women having more rupture-prone characteristics compared to younger women.

Age, Atherosclerosis, Cardiovascular disease, Gender, Peripheral artery disease, Plaque, Sex,
Department of Cardiology

de Bakker, M. (Marie), Timmerman, N. (Nathalie), van Koeverden, I.D. (Ian D.), de Kleijn, D.P.V, de Borst, G.J, Pasterkamp, G, … den Ruijter, H.M. (2020). The age- and sex-specific composition of atherosclerotic plaques in vascular surgery patients. Atherosclerosis, 310, 1–10. doi:10.1016/j.atherosclerosis.2020.07.016