• From the Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, 165 Cambridge St, Ste 400, Boston, MA 02114 (I.L.L., M.C.L., T.M., M.T.L., B.F.); Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany (I.L.L., M.C.L., D.M.); Artificial Intelligence in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, Mass (I.H., R.Z., H.J.W.L.A.); Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass (I.H., R.Z., H.J.W.L.A.); Department of Radiology and Nuclear Medicine, CARIM & GROW, Maastricht University, Maastricht, the Netherlands (I.H., H.J.W.L.A.); and School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany (T.M.).

Background Individuals eligible for lung cancer screening with low-dose CT face a higher cardiovascular mortality risk. Purpose To investigate the association between changes in epicardial adipose tissue (EAT) at the 2-year interval and mortality in individuals undergoing serial low-dose CT lung cancer screening. Materials and Methods This secondary analysis of the National Lung Screening Trial obtained EAT volume and density from serial low-dose CT scans using a validated automated deep learning algorithm. EAT volume and density changes over 2 years were categorized into typical (decrease of 7% to increase of 11% and decrease of 3% to increase of 2%, respectively) and atypical (increase or decrease beyond typical) changes, which were associated with all-cause, cardiovascular, and lung cancer mortality. Uni- and multivariable Cox proportional hazard regression models-adjusted for baseline EAT values, age, sex, race, ethnicity, smoking, pack-years, heart disease or myocardial infarction, stroke, hypertension, diabetes, education status, body mass index, and coronary artery calcium-were performed. Results Among 20 661 participants (mean age, 61.4 years ± 5.0 [SD]; 12 237 male [59.2%]), 3483 (16.9%) died over a median follow-up of 10.4 years (IQR, 9.9-10.8 years) (cardiovascular related: 816 [23.4%]; lung cancer related: 705 [20.2%]). Mean EAT volume increased (2.5 cm³/m² ± 11.0) and density decreased (decrease of 0.5 HU ± 3.0) over 2 years. Atypical changes in EAT volume were independent predictors of all-cause mortality (atypical increase: hazard ratio [HR], 1.15 [95% CI: 1.06, 1.25] [P < .001]; atypical decrease: HR, 1.34 [95% CI: 1.23, 1.46] [P < .001]). An atypical decrease in EAT volume was associated with cardiovascular mortality (HR, 1.27 [95% CI: 1.06, 1.51]; P = .009). EAT density increase was associated with all-cause, cardiovascular, and lung cancer mortality (HR, 1.29 [95% CI: 1.18, 1.40] [P < .001]; HR, 1.29 [95% CI: 1.08, 1.54] [P = .005]; HR, 1.30 [95% CI: 1.07, 1.57] [P = .007], respectively). Conclusion EAT volume increase and decrease and EAT density increase beyond typical on subsequent chest CT scans were associated with all-cause mortality in participants screened for lung cancer. EAT volume decrease and EAT density increase were associated with elevated risk of cardiovascular mortality after adjustment for baseline EAT values. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Fuss in this issue.