AI-Quantitative CT Coronary Plaque Features Associate with a Higher Relative Risk in Women: CONFIRM2-Registry

Background: Coronary plaque features are imaging biomarkers of cardiovascular risk, but less is known about sex-specific patterns in their prognostic value. This study aimed to define sex differences in the coronary atherosclerotic phenotypes assessed by artificial intelligence-based quantitative coronary computed tomography (AI-QCT) and the associated risk of major adverse cardiovascular events (MACE). Methods: Global multicenter registry (CONFIRM2) including symptomatic patients with suspicion of CAD referred for coronary CTA. AI-QCT analyzed 16 CAD features. Primary endpoint was MACE defined as death, myocardial infarction, late revascularization, cerebrovascular events, unstable angina and congestive heart failure. Results: Among 3551 patients (mean age 59±12 years, 49.5% women), MACE occurred in 3.2% of women and 6.1% of men during an average follow-up of 4.8±2.2 years. The AI-QCT features total plaque volume (TPV), noncalcified plaque (NCP), calcified plaque (CP) and percentage atheroma volume (PAV) were significantly higher in men (p<0.001), and high-risk plaque (HRP) was more prevalent (9.2% vs 2.5%, p<0.0001). Independent of age and cardiovascular risk factors, the AI-QCT derived features of TPV, NCP, CP, and PAV conferred a higher relative risk of MACE in women than men. For every 50mm3 increase in TPV, relative risk increased by 17.7% (95% CI 1.12-1.24) in women vs 5.3% (95% CI 1.03-1.07) in men (p-interaction<0.001), for NCP relative risk increased by 27.1% (95% CI 1.17-1.38) vs 11.6% (95% CI 1.08-1.15) (p-interaction = 0.0015), and for CP, by 22.9% (95% CI 1.14-1.33) vs 5.4% (95% CI 1.01-1.10) (p-interaction = 0.0012), respectively. Similarly, for PAV the risk was higher in women. The findings remained unchanged when restricted to a secondary composite endpoint (death and myocardial infarction). Conclusions: The AI-QCT plaque features TPV, NCP, CP and PAV conferred a higher relative MACE risk in women and may prompt more aggressive anti-atherosclerotic therapy and reinforced preventive interventions.