Extracranial Carotid Stenosis: Causes

Pathogenesis (development of disease)

Atherosclerosis (arteriosclerosis, hardening of the arteries) underlies carotid stenosis in more than 90% of cases. Small lesions (injury), which may be present in the arterial wall even at a young age, form the asymptomatic beginning of atherosclerosis. In the first place there is an endothelial cell damage (so-called endothelial dysfunction; endothelium = cells of the innermost wall layer facing the vessel lumen) due to an increased supply of oxidized LDL, (Low Density Lipoprotein) especially by small dense LDL particles (“small dense LDL”). The further steps of atherogenesis (development of arterial calcification) are:

  • Attachment of monocytes (belong to the white blood cells; precursors of macrophages, which play an important role in immune defense as “scavenger cells”) and platelets (blood platelets; blood cells that are important for blood clotting) to the dysfunctional endothelium.
  • Immigration of monocytes and platelets into the intima (innermost layer of the vessel wall)
  • Monocytes become macrophages and ingest LDL particles
  • Macrophages give rise to foam cells (foam-cells), which become lodged in intima and media (middle layer of arteries, depending on the type of vessel, consisting of a more or less distinct muscle layer) and lead to inflammatory reactions (→ fatty streaks; fatty streaks)
  • Endothelial cells and monocytes produce increased cytokines and growth factors (→ proliferation of smooth muscle cells of the media)
  • Migration of smooth muscle cells into the intima and synthesis of collagen and proteoglycans (extracellular matrix; extracellular matrix, intercellular substance, ECM, ECM) leads to the formation of fibrous plaques.
  • Demise of foam cells in the fibrous plaques (→ release of lipids and cholesterol); Ca2+ incorporation results in cholesterol crystals.
  • The media is completely affected by the above process in the final stage and thus loses its elasticity

Particularly dangerous are unstable plaques, the rupture of which can lead to acute vascular occlusion (e.g., apoplexy/stroke). Preferred localization of carotid stenosis are the carotid bulb (branching area) and the exit area of the internal carotid artery (ACI; internal carotid artery). In pathogenesis, the adventitia (tissue surrounding the vessel to the outside) is currently the focus of research. This is useful because it is the only way to understand the differential involvement of individual stromal areas. Another research focus in atherosclerosis research is the investigation of microbiological causes of atherosclerosis. Questions seeking answers are: What causes infection with the vasa vasorum (smallest arteries and veins found in the wall of larger blood vessels) and why are they damaged? Why do localized infections affect vessels far from the focus, such as the aorta (main artery)? How can environmental toxins, infections, and other factors trigger the same mechanism of damage? For more on the pathogenesis of atherosclerosis, see Atherosclerosis/Causes below.

Etiology (Causes)

Biographic Causes

  • Family history – coronary artery disease (CAD; coronary artery disease) or myocardial infarction (myocardial infarction) in close relatives (1st degree) – especially if men develop the disease before age 55 or women before age 65, respectively; presence of atherosclerosis-related vascular disease
  • Age – increasing age

Behavioral causes

  • Nutrition
    • Malnutrition and overeating, e.g., excessive caloric intake and high-fat diet (high intake of saturated fat).
    • Micronutrient deficiency (vital substances) – see atherosclerosis / prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol (woman: > 40 g/day; man: > 60 g/day) – (hypertriglyceridemia).
    • Tobacco (smoking) – smoking is one of the key risk factors for atherosclerosis and, therefore, for all cardiovascular disease
  • Physical activity
    • Physical inactivity
  • Psycho-social situation
    • Psychological stress
    • Sleep disturbances in the climacteric
    • Stress
  • Overweight (BMI ≥ 25; obesity).
  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type)-there is a high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)); increased abdominal fat has a strong atherogenic effect and promotes inflammatory processes (“inflammatory processes”)When measuring waist circumference according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
    • Men < 94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

Disease-related causes

  • Diabetes mellitus (insulin resistance)
  • Hypothyroidism (hypothyroidism) – this is usually associated with elevated serum cholesterol levels; latent (subclinical) hypothyroidism is also a risk factor for atherosclerosis
  • Osteoporosis – significant risk factor for coronary heart disease (CHD): this is explained by the fact that the so-called osteoclasts (bone-degrading cells) – equally stimulate sclerosis (calcification) of the arteries.
  • Depression
  • Periodontitis (inflammation of the periodontium)
  • Metabolic syndrome
  • Arterial hypertension (high blood pressure)

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

X-rays

Other causes

  • Infections with chlamydia
  • Chronic infections – for example, urogenital tract, respiratory tract.