Atherosclerosis is a chronic pathological process in which lipid, inflammatory cells, fibrous tissue and other components accumulate within the walls of medium and large arteries, producing atherosclerotic plaques. It is a major underlying mechanism of coronary artery disease, ischaemic stroke and peripheral arterial disease. The process begins with dysfunction of the arterial endothelium and retention of atherogenic lipoproteins within the arterial wall, followed by inflammatory and cellular responses that produce plaque formation and remodelling. Atherosclerosis is therefore not simply “fat blocking arteries”; it is a complex inflammatory and structural disease of the arterial wall.
Low-density lipoprotein cholesterol is a major causal factor in Atherosclerosis. When atherogenic lipoproteins enter and become retained within the arterial intima, they can undergo chemical modification and stimulate inflammatory responses. Monocytes enter the vessel wall and differentiate into macrophages, which can ingest modified lipids and become foam cells. Smooth-muscle cells migrate and proliferate, while extracellular matrix production contributes to formation of a fibrous cap. Over time, plaques can enlarge, calcify, develop necrotic lipid-rich cores and alter the mechanical properties of the artery.
Atherosclerotic plaques can be stable or vulnerable to disruption, although plaque biology exists on a continuum rather than as a simple binary classification. A fibrous cap can cover a lipid-rich necrotic core, while inflammatory activity can weaken the cap. Plaque rupture or erosion can expose thrombogenic material to circulating blood and trigger platelet activation and thrombus formation. A rapidly developing thrombus can abruptly reduce arterial blood flow and cause myocardial infarction, ischaemic stroke or acute limb ischaemia depending on the affected vascular territory. Thus, severe obstruction and acute thrombosis are related but distinct mechanisms.
Risk factors include elevated LDL cholesterol, hypertension, tobacco exposure, diabetes, obesity, physical inactivity, chronic inflammatory states, age and genetic predisposition. Familial hypercholesterolaemia is an inherited condition that can produce very high LDL cholesterol and markedly accelerate atherosclerotic disease. Smoking damages vascular function and promotes inflammation and thrombosis, while hypertension contributes mechanical stress to the arterial wall. Diabetes promotes vascular injury through multiple metabolic pathways. Risk factors often cluster, making overall cardiovascular-risk assessment more informative than considering any one factor in isolation.
Atherosclerosis differs from Arteriosclerosis, although the terms are sometimes incorrectly treated as synonyms. Arteriosclerosis is a broader term describing hardening or loss of elasticity of arteries and encompasses several pathological processes, including atherosclerosis and certain forms of arteriolosclerosis. Atherosclerosis specifically concerns plaque formation within the arterial wall. Calcification can occur within atherosclerotic plaques but is not itself synonymous with atherosclerosis. The disease also differs from an acute arterial thrombosis because thrombosis can be a complication of plaque disruption rather than the definition of the underlying arterial disease.
Prevention and treatment focus heavily on reducing modifiable cardiovascular risk. LDL cholesterol reduction through dietary measures and lipid-lowering medicines such as statins can reduce cardiovascular events in appropriately selected people. Blood-pressure control, smoking cessation, diabetes management, physical activity and weight management can further reduce risk. Treatment intensity depends on baseline risk and whether established atherosclerotic cardiovascular disease is present. Established disease may require antiplatelet therapy, revascularisation or other interventions, but these treatments are not automatically appropriate for every person with risk factors.
Atherosclerosis can remain clinically silent for decades before producing symptoms. A narrowing becomes particularly important when it limits blood flow sufficiently during increased demand, while sudden plaque disruption can cause acute events without an extremely severe pre-existing narrowing. Common clinical consequences include angina, myocardial infarction, transient ischaemic attack, ischaemic stroke and peripheral arterial disease. Because plaque develops systemically, disease in one arterial territory can indicate increased risk elsewhere.
A common misconception is that Atherosclerosis is an inevitable consequence of ageing and therefore cannot be meaningfully modified. Age increases risk, but LDL exposure, smoking, blood pressure, diabetes and other factors influence disease development and progression. Another misconception is that a person must have symptoms before plaque is present; early disease is frequently asymptomatic. Atherosclerosis is best understood as a chronic arterial-wall disease driven by lipid retention, inflammation and structural remodelling, with clinical events occurring when plaques obstruct flow or become complicated by thrombosis.
