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-mm ³ 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.

Background: A brain–heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesized anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls.Methods: Anatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls.Results: Significantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p < 0.01) lower functional connectivity in TTS patients compared to healthy controls, particularly in the connections originating from the right insular cortex, temporal lobes, and precuneus.Conclusion: In the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes.Graphic