Sex-Specific Prognostic Value of Automated Epicardial Adipose Tissue Quantification on Serial Lung Cancer Screening Chest CT

Aims Epicardial adipose tissue (EAT) is a metabolically active fat depot associated with coronary atherosclerosis and cardiovascular (CV) risk. While EAT is a known prognostic marker in lung cancer screening, its sex-specific prognostic value remains unclear. This study investigated sex differences in the prognostic utility of serial EAT measurements on low-dose chest CTs. Methods and results We analyzed baseline and two-year changes in EAT volume and density using a validated automated deep-learning algorithm in 24,008 heavy-smoking participants from the National Lung Screening Trial (NLST). Sex-stratified multivariable Cox models, adjusted for CV risk factors, BMI, and coronary artery calcium (CAC), assessed associations between EAT and all-cause and CV mortality (median follow-up 12.3 years [IQR: 11.9–12.8], 4,668 [19.4%] all-cause deaths, 1,083 [4.5%] CV deaths). Women (n = 9,841; 41%) were younger, with fewer CV risk factors, lower BMI, fewer pack-years, and lower CAC than men (all P < 0.001). Baseline EAT was associated with similar all-cause and CV mortality risk in both sexes (max. aHR women: 1.70; 95%-CI: 1.13–2.55; men: 1.83; 95%-CI: 1.40–2.40, P-interaction=0.986). However, two-year EAT changes predicted CV death only in women (aHR: 1.82; 95%-CI: 1.37–2.49, P < 0.001), and showed a stronger association with all-cause mortality in women (aHR: 1.52; 95%-CI: 1.31–1.77) than in men (aHR: 1.26; 95%-CI: 1.13–1.40, P-interaction=0.041). Conclusion In this large lung cancer screening cohort, serial EAT changes independently predicted CV mortality in women and were more strongly associated with all-cause mortality in women than in men. These findings support routine EAT quantification on chest CT for improved, sex-specific cardiovascular risk stratification.