Coronary Artery Calcium as a Biological Staging Marker for Atherosclerosis: Aligning Preventive Therapies With Plaque...

Atherosclerosis progresses silently for years, and many first cardiovascular events occur in individuals previously categorized as low or intermediate risk. Coronary artery calcium (CAC) scoring provides a direct measure of subclinical atherosclerosis and can serve as a biologic staging marker identifying phases of plaque development in which preventive therapies exert their strongest stabilizing effects. Modern cardiometabolic therapies, including statins, proprotein convertase subtilisin/kexin type 9 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and anti-inflammatory agents, influence plaque biology through lipid reduction, metabolic improvement, endothelial support, and attenuation of inflammatory signaling. A CAC-guided approach aligns treatment intensity with plaque burden: CAC = 0 supports lifestyle-focused prevention, CAC 1-99 identifies early disease warranting pharmacologic prevention, CAC 100-299 indicates higher-risk plaque requiring intensive lipid-lowering and adjunctive therapy, and CAC ≥300 reflects a phenotype approaching secondary prevention risk. Integrating CAC into preventive strategies enables earlier detection of atherosclerosis and disease stage-guided therapy, with the potential to reduce first cardiovascular events.