Age stratified differences in coronary artery plaque phenotype in women and men with non-obstructive coronary artery disease

Abstract Background Development of coronary artery disease (CAD) and risk of acute cardiac events differ between women and men during the life span. The aim of this study was therefore to characterize sex differences in coronary artery plaque phenotype among patients with symptomatic non-obstructive CAD in different age groups. Methods Advanced coronary artery plaque phenotyping by coronary computed tomography angiography was performed in 606 patients (31% women) with symptomatic non-obstructive CAD from the Norwegian Registry of Invasive Cardiology. A 1:1 sex-matched study design ensured equal distribution of the sexes in the different age groups. We assessed total plaque burden adjusted for vessel volume and plaque composition consisting of dense calcium, fibrous, fibro-fatty, and necrotic core. Patients were further stratified into age groups of ≤50, 51-64, and ≥65 years to explore the relationship between age and sex on coronary artery plaque phenotype. Results In the study population, patients ≥65 years had a higher prevalence of hypertension, higher calcium score, coronary artery segment involvement score and total plaque burden, whereas the prevalence of obesity was lower compared to patients aged 51-64 and ≤50 years (all p<0.05). The prevalence of smoking, diabetes and statin treatment was similar between groups. A two-way analysis of variance demonstrated an interaction between sex and age group on total plaque burden (F [2, 600] =3.431, p=0.33), where women aged 51-64 and ≥65 years had a higher total plaque burden compared to men (p=0.002 and p<0.001, respectively, Figure 1). Plaque composition in women ≥65 years was characterized by an increased proportion of stable dense calcified plaques compared to men and younger women (all p<0.05), whereas men ≥65 years had a higher proportion of vulnerable necrotic core plaque phenotype (p<0.001). Women showed consistently lower proportions of more vulnerable fibro-fatty plaques compared to men across all age groups (all p<0.05, Figure 2). Conclusions In non-obstructive CAD, higher total plaque burden was associated with older age and female sex. Women had a lower proportion of vulnerable fibro-fatty plaques across all age groups and a higher proportion of stable dense calcified plaques at an older age compared to men. Future longitudinal studies on coronary artery plaque phenotype during the life span will increase the understanding of sex differences in CAD development and may contribute to customise risk stratification in women and men.Figure 1.Total plaque burdenFigure 2.Compositional plaque burden