Assessment of Coronary Inflammatory Risk From Noncontrast Cardiac Computed Tomography

Importance Individuals with low or minimal coronary artery calcification (CAC) are considered at low cardiovascular risk, but a substantial absolute number of cardiovascular events occur in this population; assessment of coronary inflammation using the fat attenuation index (FAI) score may identify residual inflammatory risk beyond CAC score. Objective To assess whether coronary inflammation measured on coronary computed tomography angiography (CCTA) or noncontrast cardiac CT (NCCT) identifies individuals at high cardiovascular risk independent of CAC burden. Design, Setting, and Participants In this cohort study, a novel artificial intelligence algorithm for measuring FAI score on NCCT was trained and tested in an independent, multicenter, longitudinal cohort of consecutive individuals undergoing clinically indicated CCTA and NCCT for CAC score between 2010 and 2021, with median (IQR) follow-up of 6.7 (4.6-10.0) years. Data were analyzed from January 2010 to March 2024. Exposure Agatston CAC score and coronary inflammation from both CCTA (CCTA FAI score, established biomarker) and NCCT (NC FAI score, novel biomarker). Main Outcomes and Measures The primary outcome was cardiovascular (CV) mortality; the secondary outcome was major adverse cardiovascular events (MACE), comprising myocardial infarction, new-onset heart failure, or CV death. Results The derivation cohort included 6818 individuals (median [IQR] age, 61 [51-71] years; 3543 female participants [52.0%]), and the external validation clinical outcomes cohort included 19 110 individuals (median [IQR] age, 56.0 [48.0-64.0] years; 9289 female participants [48.6%]). During follow-up, 536 CV deaths and 1727 MACE occurred. FAI scores independently stratified CV mortality risk across CAC score categories, with the strongest associations among individuals with CAC score of 0. Adding CCTA FAI score or NC FAI score to CAC score significantly improved risk discrimination (area under the curve increased from 0.76 to 0.81 and 0.80, respectively; P < .001), reclassification (net reclassification index), and net benefit across all risk thresholds. Among 89 CV deaths in individuals with CAC score of 0 and 138 CV deaths with CAC score of 1 through 99, 44.9% and 44.2% had NC FAI score above the 75th percentile, respectively. Among individuals with CAC score of 0, CV mortality rates increased from 1.4 to 4.0 per 1000 person-years for those with NC FAI score above the 75th percentile, and MACE rates increased from 5.9 to 13.3 per 1000 person-years. Conclusions and Relevance Per the results of this cohort study, NC FAI score provides prognostic performance comparable to CCTA FAI score and improves cardiovascular risk prediction and reclassification beyond CAC score. Elevated FAI score, derived from either CCTA or NCCT, should be interpreted as a risk-enhancing factor that may prompt intensification of established, evidence-based preventive measures and may serve as a potential future gatekeeper for the use of targeted anti-inflammatory treatments.