Longitudinal coronary plaque phenotyping and precision prevention in asymptomatic adults

Background Preventive treatment in people without symptoms is usually guided by clinical risk scores and coronary artery calcium (CAC). However, CAC does not show non-calcified plaque, plaque composition or coronary narrowing. Coronary CT angiography (CCTA) provides this information, but routine CCTA screening is unlikely to be efficient or feasible. The central clinical question is therefore not whether CCTA detects more disease, but in whom that additional information identifies adverse disease trajectories or improves preventive management. Overall Aim To determine when clinical risk assessment and CAC misclassify subclinical coronary atherosclerosis, how CCTA-defined disease evolves, and whether imaging-guided prevention alters adverse plaque progression. Primary Hypotheses 1. Among asymptomatic adults, a CCTA-defined discordant phenotype - characterised by greater total and non-calcified coronary plaque burden than expected from clinical risk assessment and CAC - will be associated with greater five-year plaque progression and development of adverse plaque features, independent of preventive treatment and achieved LDL cholesterol. 2. The effect of CAC-guided preventive management on non-calcified plaque progression will differ according to baseline CCTA-defined plaque discordance, with the greatest treatment benefit anticipated among participants with greater plaque burden than expected from their clinical risk and CAC. SIGNIFICANCE AND EXPECTED OUTCOMES This PhD will move beyond simply showing that CCTA detects additional plaque. It will define when clinical risk and CAC are sufficient, when a CAC=0 result provides false reassurance, and whether additional CCTA information identifies a different response to a preventive strategy/treatment. Expected outputs include a risk–anatomy phenotype, evidence on its longitudinal significance, and an RCT-informed estimate of treatment-selection value. The work will support more selective use of CCTA, reduce indiscriminate imaging, and identify at-risk population most appropriate for a future CCTA-guided clinical outcomes trial.