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

Background: Coronary artery disease (CAD) progression and risk of cardiac events differ between women and men during the lifespan. Accordingly, we aimed to explore the impact of sex and age on plaque phenotype in non-obstructive CAD.

Method: We included 1189 patients with non-obstructive CAD (48% women) from the Norwegian Registry of Invasive Cardiology and quantitatively assessed each patient's plaque phenotype by coronary CT angiography. Plaque subtypes included calcified (>350 Hounsfield units [HU]), fibrous (131 to 350 HU), fibrofatty (76 to 130 HU) and necrotic core plaques (-30 to 75 HU). The impact of sex on plaque phenotype was assessed after age stratification (≤50, 51-64 and ≥65 years).

Results: Total plaque burden adjusted for vessel volume was higher in middle-aged and older women compared with men (all p<0.05). Women had lower proportions of fibrofatty plaques compared with men across all age groups, while middle-aged and older women had higher proportions of calcified and fibrous plaques compared with men. Middle-aged and older men had higher proportions of necrotic core plaques compared with women (all p<0.05). After adjusting for cardiovascular risk factors, female sex remained independently associated with total plaque burden (β=1.0 [0.5 to 1.5], p<0.001), and younger age and male sex with fibrofatty plaque burden (β=-2.8 [-4.4 to -1.2], p<0.001, and β=-3.8 [-4.9 to -2.8], p<0.001, respectively).

Conclusion: In non-obstructive CAD, female sex was associated with a higher total plaque burden, whereas male sex and younger age were associated with a higher proportion of vulnerable fibrofatty plaques. Our results highlight important sex differences in plaque phenotypes among patients with non-obstructive CAD during the lifespan, which may impact risk-stratification.

Trial registration number: NCT04009421.