From biology to imaging: Rethinking vulnerable plaques in coronary artery disease

Background: Coronary artery disease continues to be a leading cause of morbidity and mortality worldwide with atherosclerosis as its underlying cause. Initial pathological studies emphasized plaque rupture as the main trigger of acute coronary syndromes (ACS). Subsequent observations identified alternative substrates, such as plaque erosion and calcific nodules, while research has increasingly recognized atherosclerosis as a chronic, inflammatory and panvascular disorder. Methods and Results: This review critically examines current evidence on plaque vulnerability and destabilization, with a focus on intravascular imaging (IVI) findings. Optical coherence tomography, intravascular ultrasound and near-infrared spectroscopy have enabled detailed in vivo characterization of high-risk phenotypes, including thin-cap fibroatheromas, lipid-rich cores, macrophage infiltration, microcalcifications and intraplaque haemorrhage. These advances have improved pathophysiological understanding. However, the translation of imaging surrogates into prognostic tools remains uncertain. Although multiple studies have shown associations between imaging-derived vulnerability features and major cardiovascular events, lesion-specific prediction is inconsistent and preventive percutaneous treatment has not demonstrated clear benefit in terms of survival or myocardial infarction reduction. By contrast, intensive lipid-lowering and anti-inflammatory strategies have consistently promoted plaque stabilization and regression. Conclusions: Despite the insights offered by high-resolution IVI, vulnerable plaques should be considered as markers of global patient risk rather than reliable predictors of culprit lesions. Current evidence does not support routine pre-emptive intervention on non-culprit vulnerable plaques. Instead, optimized medical therapy remains the cornerstone of management. Future progress will depend on longitudinal studies integrating imaging, biology and clinical outcomes to bridge the gap between mechanistic understanding and therapeutic application.