Abstract

Abstract Background Qualitative high-risk plaque (HRP) features detected on coronary computed tomography angiography (CCTA) are associated with increased risk of adverse cardiac events. Coronary inflammation is a key determinant of plaque progression and instability and can now be captured on routine CCTA as inflammation-induced changes in perivascular adipose tissue composition, detectable by the perivascular Fat Attenuation Index (FAI). Purpose To explore the ability of perivascular FAI phenotyping to stratify the cardiac risk associated with the presence of adverse plaque morphology on routine CCTA. Methods This was a post-hoc analysis of the CRISP-CT (Cardiovascular RISk Prediction using Computed Tomography) study, which involved 3912 patients (mean age 55.7±13.7 years, 41.1% females) undergoing clinically-indicated CCTA in two centres (Erlangen, Germany & Cleveland, USA). Perivascular FAI mapping was performed around the proximal 10–50 mm of the right coronary artery and defined as the weighted mean attenuation of the perivascular adipose tissue, as previously validated. HRP features were defined as the presence of ≥1 of the following: positive remodelling, low-attenuation plaque, spotty calcification or napkin-ring sign (A). Cox regression models (adjusted for age, sex, epicardial fat volume and coronary artery disease [≥50% stenosis]) were used to explore the association between FAI, HRP, and future major adverse cardiac events (MACE: defined as the composite of cardiac mortality and non-fatal myocardial infarction). Results At baseline the prevalence of HRP and high FAI (≥-70.1 Hounsfield Units, as previously validated) was 23.6% (n=923) and 24.3% (n=952) respectively. Over a median follow-up period of 5.6 years (25th-75th percentile: 4.0–7.0 years) there were 91 confirmed MACE. Patients with both HRP features (HRP+) and high FAI (FAI+) had a 6.3-fold (P<0.001) higher adjusted risk of MACE compared to individuals with neither of these risk features (HRP-/FAI-) (B). Furthermore, patients without HRP features but with high FAI (HRP-/FAI+) had a 4.9-fold (P<0.001) higher adjusted risk of MACE compared to the reference (HRP-/FAI-) group. However, among patients with low FAI, there was no significant difference in the prospective risk of MACE between HRP+ and HRP- patients (P=0.87). Conclusion FAI is associated with an increased risk of adverse events in both patients with and without high-risk plaques, highlighting coronary inflammation as a major determinant of plaque vulnerability, independent of adverse plaque morphology. Non-invasive characterization of coronary inflammation using CCTA-derived FAI can improve risk stratification by supplementing the traditional anatomical assessment of the coronary vasculature with a functional marker of disease activity. Acknowledgement/Funding British Heart Foundation, National Institute of Health Research, Oxford Biomedical Research Centre

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