- Clinical science
Atherosclerosis is the most common type of arteriosclerosis, or thickening and stiffening of the arterial wall. Major risk factors include smoking, diabetes mellitus, arterial hypertension, dyslipidemia, family history of early heart disease, and advanced age. The pathogenesis is a complicated process precipitated by endothelial damage, which leads to an invasion of inflammatory cells into the tunica intima and adhesion of platelets to the disrupted endothelium. Invading smooth muscle cells (SMCs) and macrophages take up cholesterol from oxidized low-density lipoprotein (LDL) in the vessel wall. They then become foam cells, which accumulate in early atherosclerotic lesions (fatty streaks), triggering the production of extracellular matrix (e.g., collagen). This leads to the formation of fibrous plaques (foam cells, extracellular matrix, free cholesterol, and cellular debris), which may rupture and lead to thrombosis. Common sites of atherosclerosis include the abdominal aorta, coronary arteries, popliteal arteries, and carotid arteries. Depending on the location, atherosclerosis may lead to a variety of conditions, such as arterial , , (CHD), (PAD), , subcortical (Binswanger's disease), thrombosis (e.g., and ), and .
Arteriosclerosis: arterial wall thickening and elasticity loss with variable pathogenesis
- Atherosclerosis: (most common type of arteriosclerosis): multifactorial inflammatory disease of the intima, manifesting at points of hemodynamic shear stress
- : dystrophic calcification of the media
Arteriolosclerosis: hardening of arterioles
- Hyaline arteriolosclerosis
- Hyperplastic arteriolosclerosis
The terms “arteriosclerosis” and “atherosclerosis” are often used synonymously!
- Leading cause of vascular disease worldwide
- Sex: ♂ > ♀
Epidemiological data refers to the US, unless otherwise specified.
- : elevated LDL cholesterol (values > 160 mg/dL represent significant risk in a patient with no other risk factors) and reduced HDL cholesterol (♂ < 40 mg/dL or ♀ < 50 mg/dL)
- Family history: cardiovascular events in first-degree relatives below the age of 55 (♂)/65 (♀)
- Age (males ≥ 45 years, females ≥ 55 years)
- High homocystine level ()
- High fibrinogen levels
- Increased alcohol consumption
The term obesity, elevated triglycerides, low high-density lipoprotein (HDL), diabetes mellitus, and arterial hypertension. refers to the presence of at least 3 of the following risk factors:
- Chronic stress on the endothelium
Endothelial dysfunction, which leads to
- Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
- Adhesion of platelets to the damaged vessel wall → platelets release inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)
- PDGF stimulates migration and proliferation of smooth muscle cells (SCM) in the tunica intima and mediates differentiation of fibroblasts into myofibroblasts
- Inflammation of the vessel wall
- Macrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells.
- Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
- Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) → development of a fibrous plaque (atheroma)
- Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
- Plaque rupture → exposure of thrombogenic material (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material
Common sites (in order of frequency)
- Weakening of vessel wall: arterial or
- Demand-supply mismatch: ; (CHD), ; (PAD), , and subcortical (Binswanger disease)
- Thrombosis: ,
- : atherosclerosis of the renal artery → activation of the renin-angiotensin-aldosterone system
- Weight reduction
- Dietary modification
- Moderate aerobic exercise
- Smoking cessation
- Moderate consumption of alcohol (about 1–2 glasses of wine or beer per day) presumably has a protective effect.
- Medical treatment: Treat , and
The most significant therapeutic step patients with vascular disease can take is stopping smoking!