The study investigated whether changes in epicardial adipose tissue (EAT), measured from serial low-dose chest CTs in lung cancer screening, have different prognostic implications for men vs. women focusing on all-cause and cardiovascular (CV) effects. 24,008 heavy smokers who were enrolled in the National Lung Screening Trial were the samples used for this study. A deep-learning algorithm was used to quantify EAT volume and density at a baseline level and after two years, researchers followed participants for a median of 12.3 years to assess all-cause and CV mortality. Baseline EAT was associated with increased mortality risk in both sexes, although serial changes revealed important differences. In women, two -year increases in EAT density and changes in EAT volume strongly predicted cardiovascular mortality and showed stronger associations with all-cause mortality compared to men. In men, increases in EAT volume were linked to all-cause mortality but not CV outcomes.These findings suggest that women are more vulnerable to EAT density changes which likely reflect inflammation, hormonal shifts and adipose dysfunction. Men are more affected by visceral fat expansion. This study was limited by its retrospective design and reliance on a heavy-smoking predominantly white sample. The follow up imaging remained incomplete but this study does highlight the clinical utility of automated EAT quantification as a practical and preventative that can be used in lung cancer screening. Incorporating this EAT assessment into prevantive strategies could help determine more precise and sex specific CV risk classifications. This would greatly benefit women and potentially guide targeted interventions like anti-inflammatory or metabolic therapies.