Abstract Body (Do not enter title and authors here): Background
Artificial-intelligence-enabled analysis of atherosclerotic plaque characteristics on coronary computed tomography angiography (CCTA) may improve sex-specific risk prediction of cardiovascular (CV) events.

Aims
The aim of this study was to examine sex differences in CCTA-derived atherosclerotic plaque analysis in ISCHEMIA participants, and to identify any interaction between sex and the prognostic value of quantitative atherosclerosis parameters in predicting CV events.

Methods
In a post-hoc analysis, atherosclerosis imaging quantitative CT (QCT) was performed on all available CCTA scans. Interaction analysis was performed to understand the impact of female sex on the relationship between QCT variables and the outcomes of CV death or myocardial infarction (MI), all-cause death, and MI alone over a median follow-up of 3.3 years.

Results
Of the 3645 participants with CCTA available for analysis, mean age was 64 and 21% were female. Females had lower total, calcified, non-calcified, and low-density non-calcified plaque volume than males (p<0.001 for all, Table). Percent atheroma volume (PAV=total plaque volume /vessel volume x 100%) was associated with CV death or MI in all participants, and the association was stronger in females (univariate HR: 2.37, 95% confidence interval (CI) 1.79, 3.14, p<0.001) than men (HR: 1.70, 95% CI 1.45, 2.00, p<0.001). There was a significant interaction showing accentuated risk of CV death or MI associated with greater PAV among females vs. males (HR for female*PAV: 1.42, 95% CI 1.03, 1.95, p=0.032, Figure), mainly driven by risk for MI.

Conclusions
In ISCHEMIA, females presenting with moderate or severe ischemia and obstructive CAD had less atherosclerotic plaque burden of all subtypes and less adverse plaque characteristics identified by CCTA than men. The risk associated with greater atherosclerotic burden (PAV) was higher among female participants than males for the composite outcome of CV death or MI.