Hyperlipidemia

Hyperlipidemia
Classification and external resources
File:Hyperlipidaemia - lipid in EDTA tube.jpg A 4mL sample of hyperlipidemic blood with lipids separated into the top fraction. (Sample is in an EDTA collection tube.)
ICD-10	E78.
ICD-9	272.0-272.4
DiseasesDB	6255
MeSH	D006949

Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia (British English) is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood. It is the most common form of dyslipidemia (which also includes any decreased lipid levels).

Lipids (fat-soluble molecules) are transported in a protein capsule, and the size of that capsule, or lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.

Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a modifiable risk factor for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.

Classification

Hyperlipidemias may basically be classified as either familial (also called primary) caused by specific genetic abnormalities, or acquired (also called secondary) when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism. Also, hyperlipidemia may be idiopathic, that is, without known cause.

Hyperlipidemias may also be classified directly into which types of lipids are elevated, that is hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of Lipoprotein(a) may also be classified as a form of hyperlipidemia.

Familial (primary)

Familial hyperlipidemias are classified according to the Fredrickson classification which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation. It was later adopted by the World Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions. It remains a popular system of classification, but is considered dated by many.

Fredrickson classification of Hyperlipidemias

Hyperlipoproteinemia	OMIM	Synonyms	Defect	Increased lipoprotein	Main symptoms	Treatment	Serum appearance
Type I (rare)	238600	Buerger-Gruetz syndrome, or Familial hyperchylomicronemia	Decreased lipoprotein lipase (LPL) or altered ApoC2	Chylomicrons	Abdominal pain (from pancreatitis), lipemia retinalis, eruptive skin xanthomas, hepatosplenomegaly	Diet control	Creamy top layer
Type IIa	144400	Familial hypercholesterolemia	LDL receptor deficiency	LDL	Xanthelasma, arcus senilis, tendon xanthomas	Bile acid sequestrants, statins, niacin	Clear
Type IIb	144400	Familial combined hyperlipidemia	Decreased LDL receptor and increased ApoB	LDL and VLDL		Statins, niacin, fibrate	Clear
Type III (rare)	107741	Familial dysbetalipoproteinemia	Defect in Apo E 2 synthesis	IDL		Fibrates, statins	Turbid
Type IV	144600	Familial hyperlipemia	Increased VLDL production and Decreased elimination	VLDL		Fibrate, niacin], statins	Turbid
Type V (rare)	144650	Endogenous hypertriglyceridemia	Increased VLDL production and Decreased LPL	VLDL and Chylomicrons		Niacin, fibrate	Creamy top layer & turbid bottom

Hyperlipoproteinemia type I

Main article: Type I hyperlipoproteinemia

Type I hyperlipoproteinemia is a form of hyperlipoproteinemia associated with deficiencies of lipoprotein lipase.

Hyperlipoproteinemia type II

Hyperlipoproteinemia type II, by far the most common form, is further classified into type IIa and type IIb, depending mainly on whether there is elevation in the triglyceride level in addition to LDL cholesterol.

Type IIa

Main article: Familial hypercholesterolemia

This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma and premature cardiovascular disease. The incidence of this disease is about 1 in 500 for heterozygotes, and 1 in 1,000,000 for homozygotes.

Type IIb

The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.

• Familial combined hyperlipoproteinemia (FCH)
• Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)

Hyperlipoproteinemia type III

This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Prevalence is 0.02% of the population.

Hyperlipoproteinemia type IV

This form is due to high triglycerides. It is also known as hypertriglyceridemia (or pure hypertriglyceridemia). According to the NCEP-ATPIII definition of high triglycerides (>200 mg/dl), prevalence is about 16% of adult population.

Hyperlipoproteinemia type V

This type is very similar to type I, but with high VLDL in addition to chylomicrons.

It is also associated with glucose intolerance and hyperuricemia

Unclassified familial forms

Non-classified forms are extremely rare:

• Hypo-alpha lipoproteinemia
• Hypo-beta lipoproteinemia (prevalence 0.01-0.1%)

Acquired (secondary)

Acquired hyperlipidemias (also called secondary dyslipoproteinemias) may mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome. The most common causes of acquired hyperlipidemia are:

• diabetes mellitus
• Use of drugs such as diuretics, beta blockers, and estrogens

Other conditions leading to acquired hyperlipidemia include:

• Hypothyroidism
• renal failure
• nephrotic syndrome
• alcohol usage
• Some rare endocrine disorders and metabolic disorders

Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia. Specific lipid-lowering therapy may be required in certain circumstances.

Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food

Management

For treatment of type II, dietary modification is the initial approach but many patients require treatment with statins (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride level is markedly raised, fibrates may be preferable due to their beneficial effects. Combination treatment of statins and fibrates, while highly effective, causes a markedly increased risk of myopathy and rhabdomyolysis and is therefore only done under close supervision. Other agents commonly added to statins are ezetimibe, niacin and bile acid sequestrants. Dietary supplementation with fish oil is also used to reduce elevated triglycerides, with the greatest effect occurring in patients with the greatest severity. There is some evidence for benefit of plant sterol-containing products and ω₃-fatty acids

External links

• The Fredrickson papers (with photos from early lipoprotein research)
• 745209914 at GPnotebook

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