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 computed tomography (AI-QCT) and the associated risk of major adverse cardiovascular events (MACEs). Methods: Global multicenter registry including symptomatic patients with suspicion of coronary artery disease referred for coronary computed tomography angiography. AI-QCT analyzed 16 coronary artery disease features. The primary end point 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, noncalcified plaque, calcified plaque, and percentage atheroma volume were significantly higher in men (P<0.001), and high-risk plaques were more prevalent (9.2% versus 2.5%; P<0.0001). Independent of age and cardiovascular risk factors, the AI-QCT-derived features of total plaque volume, noncalcified plaque, calcified plaque, and percentage atheroma volume conferred a higher relative risk of MACE in women than men. For every 50-mm3 increase in total plaque volume, relative risk increased by 17.7% (95% CI, 1.12-1.24) in women versus 5.3% (95% CI, 1.03-1.07) in men (P$_{interaction}$<0.001); for noncalcified plaque, relative risk increased by 27.1% (95% CI, 1.17-1.38) versus 11.6% (95% CI, 1.08-1.15; P$_{interaction}$=0.0015); and for calcified plaque, relative risk increased by 22.9% (95% CI, 1.14-1.33) versus 5.4% (95% CI, 1.01-1.10; P$_{interaction}$=0.0012), respectively. Similarly, for percentage atheroma volume, the risk was higher in women. The findings remained unchanged when restricted to a secondary composite end point (death and myocardial infarction). Conclusions: The AI-QCT plaque features, total plaque volume, noncalcified plaque, calcified plaque, and percentage atheroma volume, conferred a higher relative MACE risk in women and may prompt more aggressive antiatherosclerotic therapy and reinforced preventive interventions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04279496.