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Why does familial hypercholesterolemia raise the risk of early coronary heart disease?
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cardiovascular disease
This micrograph shows a cross section of a coronary artery narrowed by an atherosclerotic plaque (purplish matter inside the artery). Most heart attacks are caused by the rupture of an atherosclerotic plaque, which triggers the formation of a clot that abruptly blocks blood flow to part of the heart muscle.
Familial hypercholesterolemia increases the risk of early coronary heart disease primarily due to a genetic deficiency of LDL receptors on cell surfaces, particularly in the liver.12
This deficiency prevents the efficient uptake of LDL cholesterol from the blood into cells. Consequently, two pathological processes occur:
- Accumulation: High levels of circulating LDL cholesterol deposit on the walls of arteries, leading to atherosclerosis, which is the abnormal thickening and hardening of arterial walls.12
- Overproduction: Because cells lack sufficient internal cholesterol, normal feedback inhibition mechanisms fail. This relieves enzymes from regulation, causing the body to synthesize excessive amounts of additional cholesterol.12
These factors result in severely elevated blood cholesterol from birth. In individuals who are homozygous for the condition, this leads to severe vascular disease in early childhood and a high likelihood of heart attack by age 20.12