Coronary artery calcium: from risk prediction to treatment allocation and clinical trials

Coronary artery calcium (CAC) is a direct measure of an individual's coronary atherosclerotic burden. Higher levels of CAC are strongly associated with an increased risk of cardiovascular disease (CVD) events and individuals with very high CAC levels have a CVD risk similar to stable persons with a prior CVD event. Conversely, the absence of CAC (CAC=0) is associated with a low long-term risk of CVD, even among groups classified as high risk based on traditional risk factors. Accordingly, the guideline-based role of CAC in allocation of CVD prevention therapies has expanded to include both statin and non-statin medications. Beyond prevention therapies, it is now widely recognised that the total burden of atherosclerosis is a stronger risk factor for CVD than a sole focus on coronary stenosis. Furthermore, evidence is accruing to support expanding the value of CAC=0 among low-risk symptomatic patients given its very high negative predictive value for ruling out obstructive coronary artery disease. There is now an appreciation of the value of routine assessment of CAC on all non-gated chest CTs and with the advent of artificial intelligence, automated interpretation is now possible. Additionally, CAC is now firmly established in randomised trials as a tool to identify high-risk patients most likely to benefit from pharmacotherapies. Future studies incorporating measures of atherosclerosis beyond the Agatston score will lead to continued refinement of CAC scoring, further improvements in personalisation of CVD risk prediction and more individualised allocation of prevention therapies to the patients at highest CVD risk.