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Hypercholesterolemia (literally: high blood cholesterol) is the
presence of high levels of cholesterol in the blood. It is not a
disease but a metabolic derangement that can be secondary to many
diseases and can contribute to many forms of disease, most notably
There is a number of secondary causes for high
- Diabetes mellitus and syndrome X
- Kidney disease (nephrotic syndrome)
Classically, hypercholesterolemia is categorised by its appearance on
lipoprotein electrophoresis by the Fredrickson classification.
Type I: high chylomicrons
Type IIa: high LDL
Type IIb: high LDL and VLDL
Type III: high chylomicrons and IDL (intermediate density lipoprotein)
Type IV: high triglycerides
Type V: very similar to Type I, but with high VLDL
Non-classified forms are:
Apart from Type II and Type IV, these disorders are very rare. Some
have hereditary as well as acquired forms.
Signs and symptoms
Elevated cholesterol does not lead to specific symptoms unless it has
been longstanding. Some types of hypercholesterolaemia lead to
specific physical findings: xanthoma (thickening of tendons due to
accumulation of cholesterol), xanthalasma palpabrum (yellowish patches
above the eyelids) and arcus senilis (white discoloration of the
Longstanding elevated hypercholesterolemia leads to accelerated
atherosclerosis; this can express itself in a number of cardiovascular
- Angina pectoris, leading to PTCA or CABG
- Myocardial infarction
- Transient ischemic attacks (TIA's)
- Cerebrovascular accidents/Strokes
- Peripheral artery disease (PAOD)
If the hypercholesterolemia is hereditary, there can be a family
history of premature atherosclerosis, as well as familial occurrence
of the signs mentioned above.
When measuring cholesterol, it is important to measure its
subfractions before drawing a conclusion on the cause of the problem.
The subfractions are LDL, HDL and VLDL. VLDL levels are rarely
measured directly, but are expressed in the levels of triglycerides
(45% of triglycerides is composed of VLDL). Usually, even LDL is not
measured directly but calculated from all the other fractions (total
cholesterol minus HDL and VLDL); this method is called the Friedewald
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The treatment depends on the type of hypercholesterolemia. Types IIa
and IIb can be treated with diet, statins, fibrates, nicotinic acid,
bile acid sequestrants, LDL apheresis and liver transplantation.
In patients without any other risk factors, moderate
hypercholesterolemia is often not treated.
According to Framingham Heart Study, people with an age greater than
50 years have no increased overall mortality with either high or low
serum cholesterol levels. There is, however, a correlation between
falling cholesterol levels over the first 14 years and mortality over
the following 18 years (11% overall and 14% CVD death rate increase
per 1 mg/dL per year drop in cholesterol levels).