Plaque Progression and Rupture in Obstructive Coronary Artery Disease: A Review of Current Imaging Modalities

Atherosclerotic plaque progression and rupture are the chief determinants of acute coronary syndromes and long-term outcomes in obstructive coronary artery disease (CAD). Residual risk persists despite intensive low-density lipoprotein-lowering and contemporary secondary prevention, because vascular inflammation and microstructural frailty often remain unresolved. At the bedside, the lesion that precipitates infarction is seldom the tightest but rather the most unstable. This review integrates the mechanistic chain, from endothelial dysfunction and retention/oxidation of apolipoprotein B lipoproteins to maladaptive innate and adaptive immunity, failed efferocytosis with necrotic core expansion, and biomechanical forces that thin and fatigue the fibrous cap, with their corresponding in vivo imaging phenotypes. Thus, this study aimed to examine how intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), alongside coronary computed tomography angiography (CCTA), cardiac magnetic resonance (CMR), and positron emission tomography (PET), characterize these processes and enable longitudinal tracking of disease activity. Moreover, we briefly discuss emerging therapeutic implications of plaque imaging, focusing on how improved identification of vulnerable plaque features may inform risk stratification. Finally, we evaluate therapies that extend beyond lipid-lowering to modulate inflammatory and immune pathways, reinforce cap stability, and support a risk-adapted, trajectory-based pathway in which serial imaging and biomarkers guide treatment intensity. Together, these advances support a shift in clinical practice from stenosis-centered revascularization to imaging-guided, vulnerability-centered prevention.