Atherosclerotic risk factors

A vascular occlusion is caused by an imbalance in the hemostatic system in favor of procoagulant reactions. Faulty occurrences in the plasmatic coagulation are made responsible for thromboses in the venous system. Whether risk parameters such as APC resistance or prothrombin mutations also can be made responsible for arterial occlusions is being discussed. In the arterial flow area different parameters seem to play an important role.

Formation of arterial thrombosis

In the later years the knowledge of at least the pathological mechanisms of arterial thrombosis has increased considerably. Arterial thrombus and vascular occlusions mainly occur on the walls of atheroscleroticly changed vessels. Other reasons such as inflammatory vessel changes or the Winiwarter-Buerger-Syndrome are rather rare.

The long period of development is characteristic for the genesis of myocardial infarctions or strokes. The actual incident happens after rupture or fissure of an atherosclerotic plaque. For the pathogenesis of the plaque it is today presumed that it happens in a 2-step-mechanism.

In the first step a “fatty streak” is formed in the sub-endothelial area. The reason for this is primarily a hypercholesterolemia, i.e. the serum levels of LDL (“low density lipoprotein”) and Lp(a) are high. These high concentrations cause an increase and deposition of LDL and Lp(a) in the sub-endothelial matrix. Free oxygen radicals start the oxidation processes. The oxidation products on the other hand are chemotactic for monocytes and T-cells. The penetrating monocytes mature to macrophages; via their scavenger-receptor these catch oxidized lipoproteins. The filled macrophages can be seen in a microscope and are called foam cells due to their appearance.

The second step is formation of the fibrous plaque. Different substances (cytokines, MCP-1, eicosanoids, growth factors and oxygen radicals) cause further monocytes to invade the sub-endothelial matrix. This creates proliferation of smooth muscle cells and formation of collagen fibers. The foam cells overload themselves with oxidized lipids, die and release their active content. In a positive feedback mechanism this leads to further growth of atherosclerotic plaques. In this narrow passage the hemodynamic pressure then becomes so high that the plaque may tear and thus release thrombotic stimuli. Platelets and von Willebrand-factor are activated, the plasmatic coagulation is running and a large stable and vessel-occluding thrombosis is formed.

Classic risk factors

  • Hyper-lipidemia
  • Smoking
  • Diabetes mellitus
  • Arterial hypertonia
  • Stress
  • Lack of physical activity
  • Overweight

Newer risk factors

  • Hyper-triglyceridemia
  • Hyper-cholesterolemia
  • High LDL-cholesterol
  • Low HDL-cholesterol
  • High Lp(a)
  • High fibrinogen
  • Hyper-homocysteinemia
  • Oxidized LDL
  • High consumption of trans fatty acids
  • Changes in the lipoprotein subclass, e. g. high IDL
  • High PAI-1-plasma level
  • Low antioxidant status
  • High leukocyte count
  • High CRP
  • Inflammations

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