Atherosclerosis and its risk factors
1. Atherosclerosis is a disease of the arteries that causes it to ‘harden' and affects both medium and large arteries.
2. It is the principal cause of heart attacks and strokes and is responsible for over 50% of all deaths in the western world, with increasing numbers in the developing countries.
3. Atherosclerosis is triggered as a response to chronic injury to the vascular endothelium due to a variety of insults, including homodynamic pressure, stress and oxidative damage (e.g. from oxLDL, homocysteine or viruses).
4. The damage increases the adhesiveness of the endothelium to leukocytes and platelets and, additionally, enhances its permeability.
When there is a damage to the arteries; monocytes, macrophages, smooth muscle cells and endothelial cells migrate to the site of injury.
5. The injury also causes the endothelium to produce agents such as cytokines, chemokines, mediators and growth factors that then cause further progression of the inflammatory response.
6. This then causes the migration and the proliferation of smooth muscle cells to form an intermediate lesion, which progresses to produce further lesions called the plaque leading to the thickening of the artery wall.
7. collagen formation and vascularisation takes place making the plaque stable and hence blocking arteries leading to stokes and heart attacks.
Risk factors of Atherosclerosis can be divided into 2 parts; genetic and environment
Genetic Mutations in the ABCA1 gene are responsible for two genetic disorders, tangier disease and familial-hypo-alpha-lipoprotein-aemia (FHA)
Tangier disease causes cholesterol deposition in macrophages throughout the body due to impairment of cellular efflux and the absence of HDL
FHA results in decreased cellular cholesterol efflux and degradation of HDL
familial hyper-cholesterol-aemia is a condition that leads to high lipid levels in the plasma due to defective removal of lipids.
Increased blood pressure Dominant disorder resulting in early onset of hypertension and stroke
Diabetes Increased predisposition to atherosclerosis
Elevated levels of homocysteine Homocystinuria - increased risk of bleeding and thrombosis
Gender Male - Below the of age 60, men develop CHD at more than twice the rate compared to women
Obesity Association with CHD has been observed in epidemiological studies
Environment risk factors of atherosclerosis
High fat diet High fat and cholesterol diet causes development of atherosclerosis
Smoking Causes lipid oxidation, production of free radicals Causes lipids to be easily taken up by scavenger receptors
Lack of exercise Significant independent associations with CHD: increase deposition of fat in arteries.
Infectious agents E.g. Chlamydia pneumonia increases inflammation and has been seen in atherosclerotic plaques.
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