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Hypercholesterolemia

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 cardiovascular disease.

Causes

There is a number of secondary causes for high cholesterol:

  • Diabetes mellitus and syndrome X
  • Kidney disease (nephrotic syndrome)
  • Hypothyroidism

Classification

Classically, hypercholesterolemia is categorised by its appearance on lipoprotein electrophoresis by the Fredrickson classification.

Type I: high chylomicrons

Type II:

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:

Hypo-alpha lipoproteinemia

Hypo-beta lipoproteinemia

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 iris).

Longstanding elevated hypercholesterolemia leads to accelerated atherosclerosis; this can express itself in a number of cardiovascular diseases:

  • 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.

Diagnosis

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 calculation.

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Treatment

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).

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