Long-term cardiac risk in individuals with low calcium score on coronary computed tomography angiography can be stratified by the pericoronary fat radiomic profile (FRP)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): UKRI, British Heart Foundation Background Inflammation in the coronaries induces macroscopic changes in perivascular adipose tissue composition, detectable by the pericoronary Fat Radiomic Profile (FRP) on coronary computed tomography angiography (CCTA). Purpose To assess the ability of FRP to stratify cardiac risk in patients with Coronary Artery Calcium (CAC) score below 100 following routine CCTA. Methods 1,575 participants from the CCTA arm of the SCOT-HEART trial (NCT01149590) eligible for image analysis were included. Pericoronary FRP mapping was performed in perivascular adipose tissue segmentations around the proximal sites of the right and left coronary arteries, as previously validated. We first tested the prognostic value of FRP in the sub-cohort of patients with CAC < 100. We further analysed a sub-group based on the absence of high risk plaque (HRP) features and obstructive coronary artery disease (CAD). The association with future incidence of major adverse cardiac events (MACE: cardiac mortality or non-fatal myocardial infarction) or a composite endpoint of MACE ± late revascularization (MACE-ReVasc) was assessed using adjusted Cox regression models [adjusted for age, sex, systolic blood pressure (SBP), diabetes mellitus (DM), body mass index (BMI), smoking, CAD (≥50% stenosis), total cholesterol, high-density lipoprotein (HDL), and HRP features]. Results In total, 1,032 patients (53.9% female sex) were found with low CAC score (CAC < 100), with a median age of 55 years. Over a mean follow-up of 4.87 ± 1.06 years, 12 MACE and 47 MACE-ReVasc were recorded. High FRP was associated with a 14.4-fold (95% CI: 3.80-54.78, p < 0.001) higher adjusted risk of MACE and a 2.8-fold (95% CI: 1.49-5.36, p = 0.001) higher adjusted risk of MACE-ReVasc (A). Addition of high FRP to a baseline model consisting of traditional risk factors (age, sex, systolic blood pressure, diabetes mellitus, BMI, smoking, CAD (≥50% stenosis), total cholesterol, HDL, HRP) significantly enhanced (deltaAUC at 5 years:0.15, p = 0.03) the model’s performance and reclassified individuals (NRI = 0.59, p = 0.02, B). Interestingly, after more rigorous filtering of the population by absence of HRP features and obstructive CAD, high FRP remained an independent predictor of MACE (n = 756, Adj.HR = 28.1, p = 0.003). Conclusion In individuals with low CAC scores the Fat Radiomic Profile biormarker significantly improves risk prediction for adverse clinical events beyond the current state-of-the-art. Non-invasive profiling of pericoronary adipose tissue using CCTA-derived FRP captures irreversible changes in perivascular adipose tissue composition associated with chronic vascular inflammation and atherosclerotic disease, and can supplement the traditional anatomical assessment of the coronary vasculature with a functional marker of disease activity.