Coronary Artery Atherosclerosis (CAA) represents the principal pathological substrate underlying ischemic heart disease (IHD), which remains the foremost cause of global morbidity and mortality. Characterized as a chronic, lipid-driven, fibro-inflammatory disease of arterial intima, atherosclerosis progresses from early subendothelial lipid accumulation to complex calcified fibroatheromas. Clinical presentations range from chronic coronary syndrome (stable angina) to acute coronary syndromes (unstable angina, NSTEMI, STEMI) triggered primarily by plaque rupture or superficial erosion with subsequent luminal thrombosis. Modern management encompasses aggressive risk-factor modification, high-intensity statin and PCSK9 inhibitor therapy, antiplatelet regimens, and catheter-based or surgical revascularization. 1. Pathophysiology and Plaque Dynamics Atherogenesis begins at arterial branch points and curvatures characterized by disturbed, non-laminar endothelial shear stress. Endothelial dysfunction facilitates the extravasation and retention of apolipoprotein B-containing lipoproteins (predominantly Low-Density Lipoprotein, LDL-C) within the subendothelial space. These entrapped lipids undergo enzymatic and oxidative modifications (oxLDL), provoking an innate immune cascade mediated by circulating monocytes and T lymphocytes. Monocytes differentiate into resident macrophages that ingest oxLDL via scavenger receptors (CD36, SRA-1), transforming into lipid-laden foam cells. Persistent lipid accumulation and impaired efferocytosis (defective clearance of apoptotic cells) trigger the formation of a necrotic core enriched with cellular debris, cholesterol crystals, and pro-thrombotic tissue factor. Simultaneously, vascular smooth muscle cells (VSMCs) migrate from the tunica media into the intima, synthesizing extracellular collagen to form a protective fibrous cap. Plaque stability is dictated by the balance between extracellular matrix synthesis by VSMCs and degradation by matrix metalloproteinases (MMPs) secreted by inflammatory macrophages. Thin-cap fibroatheromas (TCFA, cap thickness <65 µm) exhibit high vulnerability to rupture, precipitating occlusive intra-luminal thrombosis. 2. Diagnostic Modalities and Risk Stratification The diagnostic landscape for coronary atherosclerosis has advanced from purely luminal assessment to structural and molecular plaque imaging. While invasive coronary angiography (ICA) remains the gold standard for defining anatomy and guiding percutaneous intervention, non-invasive imaging now plays a pivotal role in early detection: • Coronary Computed Tomography Angiography (CCTA): Delivers high-resolution anatomical visualization of luminal narrowing, coronary artery calcium scoring (Agatston score), and adverse high-risk plaque features (positive remodeling, low attenuation, napkin-ring sign). • Intravascular Imaging (IVUS & OCT): Optical Coherence Tomography (OCT) offers micron-level resolution enabling identification of fibrous cap thickness, macrophage clustering, and microchannel formation. • Functional Ischemia Testing: Fractional Flow Reserve (FFR) and instantaneous wave-free ratio (iFR) guide hemodynamic significance before mechanical revascularization. Table 1: Atherosclerotic Risk Profile and Pathobiological Targets Treatment is tripartite: aggressive pharmacotherapy, mechanical intervention, and lifestyle restructuring. • Lipid-Lowering Therapy: Current ESC and ACC/AHA guidelines mandate >50% reduction in LDL-C and targets <55 mg/dL (1.4 mmol/L) in very-high-risk patients. Combination regimens employing high-intensity statins (atorvastatin 80 mg, rosuvastatin 40 mg), ezetimibe, and PCSK9 inhibitors (evolocumab, alirocumab) or siRNA (inclisiran) achieve profound plaque stabilization and regression. • Anti-Thrombotic Regimens: Low-dose aspirin combined with P2Y12 receptor inhibitors (ticagrelor, prasugrel, or clopidogrel) prevents post-rupture thrombosis. In selected high-risk stable CAD, dual-pathway inhibition (aspirin + low-dose rivaroxaban) significantly reduces ischemic events. • Anti-Inflammatory Approaches: Targeting the residual inflammatory risk via low-dose colchicine (0.5 mg daily) reduces cardiovascular death and recurrent MI. • Revascularization: Percutaneous Coronary Intervention (PCI) with second/third-generation drug-eluting stents (DES) and Coronary Artery Bypass Grafting (CABG) remain indicated for severe multi-vessel disease or left main stenosis.