Prognostic impact of epicardial fat volume, anatomical and functional imaging across the cardiovascular risk spectrum in patients with suspected coronary artery disease: a single-center retrospective cohort study

Background: Epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) and adverse cardiovascular outcomes; however, its prognostic relevance across different cardiovascular risk scores remains uncertain. This study evaluated the long-term prognostic significance of EAT, coronary anatomical findings, and functional ischemia in patients with suspected CAD stratified by Framingham risk score (FRS) categories. Methods: A consecutive retrospective cohort of 361 symptomatic patients who underwent both single-photon emission computed tomography/computed tomography myocardial perfusion imaging (SPECT/CT MPI) and coronary angiography (CAG) or coronary computed tomography angiography (CCTA) at baseline was analyzed. Epicardial fat volume (EFV) and coronary artery calcium score (CACS) were quantified from integrated computed tomography (CT) with SPECT/CT. Ischemia burden was defined as ≥5% ischemic myocardium on MPI, and obstructive CAD as ≥50% stenosis. Major adverse cardiovascular events (MACE) were recorded during follow-up. Results: Over a median follow-up of 4.6 years, 54 patients (15%) experienced MACE. In the multivariable analysis, EFV [adjusted hazard ratio (aHR) =2.09; 95% confidence interval (CI): 1.08-4.05; P=0.029], CACS (aHR =2.58; 95% CI: 1.39-4.80; P=0.003), and obstructive CAD (aHR =3.07; 95% CI: 1.59-5.90; P<0.001) were independently associated with MACE, while ischemia burden showed borderline significance (aHR =2.27; 95% CI: 0.94-5.49; P=0.069). EFV improved risk discrimination over FRS, CACS, obstructive CAD, and ischemia burden (all P<0.05). In the stratified analyses, CACS (aHR =2.88; P=0.017) and obstructive CAD (aHR =3.69; P=0.005) predicted MACE in low-to-intermediate FRS patients, whereas EFV (aHR =3.13; P=0.020) and ischemia burden (aHR =4.67; P=0.005) were only associated with MACE in high-risk FRS patients. EFV was significantly associated with MACE in patients with diabetes (aHR =6.61; P=0.010), but not in those without diabetes (aHR =1.45; P=0.359), with ischemia showing a similar pattern. Conclusions: EFV independently predicted long-term MACE and improved prognostic discrimination beyond clinical risk, anatomical imaging, and functional ischemia. Prognostic determinants varied by cardiovascular risk level, with anatomical markers being more informative in lower-risk patients, while EFV and functional ischemia were more informative in high-risk and diabetic patients. These findings support a risk-adapted strategy for the use of quantitative imaging biomarkers in patients with suspected CAD.