The Pathophysiology of Atherosclerosis and the Role of Lipid-Lowering Therapies
Atherosclerosis is a chronic inflammatory condition characterized by the accumulation of lipids, calcium, and inflammatory cells within the arterial walls, forming plaques. This process gradually narrows the vessel lumen and restricts blood flow, eventually leading to cardiovascular diseases, which remain the leading cause of mortality and morbidity worldwide.
The clinical management of atherosclerosis focuses on aggressive risk factor modification and the stabilization of existing plaques. High-dose statin therapy and newer biological agents, such as PCSK9 inhibitors, are used to lower circulating low-density lipoprotein levels, which is critical for slowing the rate of plaque growth and preventing rupture.
The progression of atherosclerosis begins with endothelial dysfunction, often caused by hypertension, smoking, or hyperglycemia. This allows lipoproteins to enter the subendothelial space, where they become oxidized and trigger an immune response. Macrophages that ingest these lipids become "foam cells," forming the core of the atherosclerotic plaque. As the plaque matures, a fibrous cap forms over the lipid core. If this cap becomes thin and unstable, it can rupture, leading to the formation of a thrombus (blood clot) that can completely block the artery, causing an acute heart attack or stroke.
Anti-platelet agents, such as aspirin or clopidogrel, are essential for preventing these thrombotic events in patients with established vascular disease. Furthermore, the use of advanced imaging, such as intravascular ultrasound or optical coherence tomography, allows clinicians to visualize the composition of the plaque and assess its vulnerability to rupture. Research is currently investigating anti-inflammatory therapies that target specific cytokines to reduce the "residual inflammatory risk" that persists even when lipid levels are well-controlled. By combining these advanced pharmacological and diagnostic tools, the goal is to stop the progression of atherosclerosis at its earliest stages and significantly reduce the global burden of cardiovascular events.