The long-held view of arterial calcification as passive mineral deposition — an inevitable consequence of aging — is being replaced by a far more nuanced picture with real implications for how cardiovascular risk is assessed and managed. Understanding calcification as a biologically driven process opens new therapeutic windows that were previously overlooked.
This comprehensive review synthesizes current mechanistic and clinical knowledge around coronary artery calcification (CAC), reframing it as an actively regulated biological phenomenon. Central to this process is the osteogenic transdifferentiation of vascular smooth muscle cells — essentially, vessel wall cells acquiring bone-forming characteristics under inflammatory signaling. Extracellular vesicle release and disruptions in mineral metabolism further drive calcific deposition. Critically, the review distinguishes between calcification phenotypes: micro- and spotty calcifications correlate with vulnerable, rupture-prone plaques, while dense sheet-like calcification tends to mark stable fibrocalcific lesions. This phenotypic distinction carries direct clinical weight, influencing not only risk stratification but also the technical difficulty of percutaneous coronary interventions. CAC burden increases with age, varies between sexes, and is amplified by cardiometabolic risk factors, chronic kidney disease, systemic inflammation, and genetic predisposition.
The significance here lies partly in mechanistic clarity and partly in clinical translation. The osteogenic reprogramming pathway, involving regulators like RUNX2 and BMP signaling, has been recognized for over a decade, but the integration of phenotype-specific plaque biology with interventional strategy is a maturing frontier. For health-conscious adults, the takeaway is that CAC scoring via computed tomography is now well-validated for risk stratification — but not all calcium signals the same risk. This review is a synthesis rather than a primary trial, so it reflects the weight of existing evidence rather than introducing new data. Its value lies in providing clinicians and researchers with an integrated framework that connects molecular drivers to imaging findings to intervention planning — an incremental but genuinely clarifying contribution to cardiovascular medicine.