Atherosclerosis, a common condition among older adults, is characterised by arterial wall thickening due to plaque accumulation, most notably seen on imaging as calcification within the coronary arteries.
Description
Atherosclerosis is a systemic, progressive disease affecting the intimal layer of medium to large arteries. It is characterised by the formation of fibro-fatty plaques, or atheromas, that lead to vessel wall thickening and luminal narrowing. It is the principal cause of coronary and cerebrovascular disease, which are leading causes of morbidity and mortality globally.
Pathogenesis
Atherosclerosis originates from endothelial cell injury, leading to a series of inflammatory responses. The injury permits LDL cholesterol deposition into the intimal layer of the arterial wall. These LDL particles undergo oxidation, prompting an inflammatory response. Monocytes adhere to the endothelium, migrate into the intima, and transform into macrophages, engulfing the oxidised LDL and forming foam cells. The accumulation of foam cells, along with proliferation of smooth muscle cells and deposition of extracellular matrix, leads to atheroma formation. Over time, these atheromas can rupture, leading to thrombus formation and potential acute arterial occlusion.
The formation of atheromas or plaques, typically begins in large- and medium-sized arteries. The initial changes usually appear in areas of turbulent blood flow such as arterial branch points and bifurcations. These areas are prone to endothelial damage which is a key step in the initiation of atherosclerosis. In particular, the aorta, coronary arteries, carotid arteries, and the arteries of the lower extremities are frequently affected. Within these vessels, plaques often develop in the intima, the innermost layer of the artery.
Subtypes
Atherosclerosis is a singular entity, although the specific vascular bed affected (coronary, carotid, peripheral, etc.) can lead to different clinical manifestations.
Epidemiology, Risk Factors & Associations
- Age (> 65 years)
- Male sex
- Smoking
- Hypertension
- Hypercholesterolemia
- Diabetes
- Family history of early atherosclerotic disease
Clinical Features
Clinical manifestations vary depending on the specific artery involved and the severity of the disease:
- Coronary atherosclerosis: angina pectoris, myocardial infarction
- Cerebrovascular atherosclerosis: transient ischemic attacks, stroke
- Peripheral arterial disease: intermittent claudication, critical limb ischemia
Complications
- Acute myocardial infarction
- Stroke
- Peripheral artery disease
- Abdominal aortic aneurysm
Pathological Features
Histopathology
- Macroscopic: Atherosclerotic plaques (atheromas), the hallmark lesions of atherosclerosis, consist of a central lipid core and a fibrous cap. The lipid core contains cholesterol crystals, necrotic cellular debris and foam cells, whereas the fibrous cap is composed of collagen, elastin, and smooth muscle cells. Advanced lesions may demonstrate calcification and may become complicated by ulceration, rupture, or haemorrhage.
- Microscopic: The atherosclerotic plaque is largely characterised by the accumulation of lipid-laden macrophages (foam cells), smooth muscle cells, lymphocytes, and extracellular matrix components in the intimal layer of the artery. Initial fatty streaks, characterised by lipid-laden foam cells, are seen followed by proliferation of smooth muscle cells and formation of fibrous plaques. In the advanced stage, necrosis, calcification, and neovascularisation from the vasa vasorum may be present. There may also be thinning of the fibrous cap and infiltration of the cap by inflammatory cells, particularly macrophages and T lymphocytes, which increases the risk of plaque rupture.
Serology
- Elevated LDL cholesterol
- Reduced HDL cholesterol
Biochemistry
- Elevated homocysteine and lipoprotein(a) levels may be associated with increased risk.
Serology
- Elevated LDL cholesterol
- Reduced HDL cholesterol
Biochemistry
- Elevated homocysteine and lipoprotein(a) levels may be associated with increased risk.
Radiological Features
General Features
- Characteristically demonstrates calcified plaques within the arterial walls, most commonly seen in the coronary arteries.
CT
- Non-contrast: Calcified plaques are readily identifiable as areas of increased attenuation within the arterial wall.
- C+ Arterial/Venous: Atherosclerotic plaques may be identified as areas of wall thickening and luminal narrowing.
US
- B-mode: Plaques appear as echogenic structures within the vessel lumen causing narrowing.
Grading and Staging
Atherosclerosis severity can be graded based on degree of stenosis, as measured by non-invasive imaging or angiography.
Diagnosis
Diagnosis is typically based on imaging findings in conjunction with clinical presentation and risk factors.
Differential Diagnosis
- Vasculitis: Typically presents with a younger demographic and may have systemic signs of inflammation.
- Arterial dissection: Characterised by the presence of an intimal flap and false lumen.
Prognosis
Atherosclerosis is a chronic disease and the prognosis is variable, depending on the extent of disease and the success of management.
Management
Management strategies include lifestyle modifications, pharmacotherapy (statins, antihypertensives), and invasive procedures (angioplasty, bypass grafting). Patients are usually managed by a multidisciplinary team including cardiologists and vascular surgeons.