| Hyperlipidemia |
| Classification and external resources |
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) involves abnormally elevated levels of any or all lipids and/or lipoproteins in the blood.[1] 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. 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.
Hyperlipidemias are divided in primary and secondary subtypes. Primary hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor protein), while secondary hyperlipidemia arises due to other underlying causes such as diabetes. 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.
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Contents
- 1 Classification
- 1.1 Familial (primary)
- 1.1.1 Hyperlipoproteinemia type I
- 1.1.2 Hyperlipoproteinemia type II
- 1.1.2.1 Type IIa
- 1.1.2.2 Type IIb
- 1.1.3 Hyperlipoproteinemia type III
- 1.1.4 Hyperlipoproteinemia type IV
- 1.1.5 Hyperlipoproteinemia type V
- 1.1.6 Unclassified familial forms
- 1.2 Acquired (secondary)
- 2 Management
- 3 See also
- 4 References
- 5 External links
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Classification [edit]
Hyperlipidemias may basically be classified as either familial (also called primary[2]) caused by specific genetic abnormalities, or acquired (also called secondary)[2] when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism.[2] Also, hyperlipidemia may be idiopathic, that is, without known cause.
Hyperlipidemias are also classified according to 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) [edit]
Familial hyperlipidemias are classified according to the Fredrickson classification which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation.[3] 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[who?].
Fredrickson classification of Hyperlipidemias
Hyperlipo-
proteinemia |
OMIM |
Synonyms |
Defect |
Increased lipoprotein |
Main symptoms |
Treatment |
Serum appearance |
Estimated prevalence |
| Type I |
a |
238600 |
Buerger-Gruetz syndrome, or Familial hyperchylomicronemia |
Decreased lipoprotein lipase (LPL) |
Chylomicrons |
Abdominal pain (from pancreatitis), lipemia retinalis, eruptive skin xanthomas, hepatosplenomegaly |
Diet control |
Creamy top layer |
1 in 1,000,000[4] |
| b |
207750 |
Familial apoprotein CII deficiency |
Altered ApoC2 |
| c |
118830 |
|
LPL inhibitor in blood |
| Type II |
a |
143890 |
Familial hypercholesterolemia |
LDL receptor deficiency |
LDL |
Xanthelasma, arcus senilis, tendon xanthomas |
Bile acid sequestrants, statins, niacin |
Clear |
1 in 500 for heterozygotes |
| b |
144250 |
Familial combined hyperlipidemia |
Decreased LDL receptor and increased ApoB |
LDL and VLDL |
|
Statins, niacin, fibrate |
Clear |
1 in 100 |
| Type III |
107741 |
Familial dysbetalipoproteinemia |
Defect in Apo E 2 synthesis |
IDL |
Tubo-Eruptive Xanthomas & Palmar Xanthomas |
Fibrate, statins |
Turbid |
1 in 10,000[5] |
| Type IV |
144600 |
Familial hypertriglyceridemia |
Increased VLDL production and Decreased elimination |
VLDL |
Can cause pancreatitis at high triglyceride levels |
Fibrate, niacin, statins |
Turbid |
1 in 100[6] |
| Type V |
144650 |
|
Increased VLDL production and Decreased LPL |
VLDL and Chylomicrons |
|
Niacin, fibrate |
Creamy top layer & turbid bottom |
|
Relative prevalence of familial forms of hyperlipoproteinemia
[7]
Hyperlipoproteinemia type I [edit]
Type I hyperlipoproteinemia exists in several forms:
- Lipoprotein lipase deficiency (Type Ia), due to a deficiency of lipoprotein lipase (LPL) or altered apolipoprotein C2, resulting in elevated chylomicrons, the particles that transfer fatty acids from the digestive tract to the liver.
- Familial apoprotein CII deficiency (Type Ib),[8][9] a condition caused by a lack of lipoprotein lipase activator.[10]:533
- Chylomicronemia due to circulating inhibitor of lipoprotein lipase (Type Ic)[11]
Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis and organomegaly, and lipaemia retinalis.
Hyperlipoproteinemia type II [edit]
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 [edit]
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 [edit]
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)
- Lysosomal acid lipase deficiency, often called (Cholesteryl ester storage disease)
- Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)
Hyperlipoproteinemia type III [edit]
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). Its prevalence has been estimated to be approximately 1 in 10,000.[5]
Hyperlipoproteinemia type IV [edit]
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.[6]
Hyperlipoproteinemia type V [edit]
Hyperlipoproteinemia type V 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 [edit]
Non-classified forms are extremely rare:
- Hyperalphalipoproteinemia
- Polygenic hypercholesterolemia
Acquired (secondary) [edit]
Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic primary forms of hyperlipidemia and can have similar consequences.[2] 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.[2] The most common causes of acquired hyperlipidemia are:
- diabetes mellitus[2]
- Use of drugs such as diuretics,[2] beta blockers,[2] and estrogens[2]
Other conditions leading to acquired hyperlipidemia include:
- Hypothyroidism[2]
- renal failure[2]
- nephrotic syndrome[2]
- alcohol usage[2]
- Some rare endocrine disorders[2] and metabolic disorders[2]
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[citation needed].
Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food[12]
Management [edit]
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This section requires expansion. (March 2009) |
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.[13] There is some evidence for benefit of plant sterol-containing products and ω3-fatty acids[14]
For the other types see the treatment column in the Fredrickson classification table above.
See also [edit]
- List of xanthoma variants associated with hyperlipoproteinemia subtypes
References [edit]
- ^ thefreedictionary.com > hyperlipidemia Citing:
- Dorland's Medical Dictionary for Health Consumers. 2007 by Saunders, an imprint of Elsevier
- The American Heritage Medical Dictionary. 2007, 2004 by Houghton Mifflin Company.
- ^ a b c d e f g h i j k l m n o Chait A, Brunzell JD (June 1990). "Acquired hyperlipidemia (secondary dyslipoproteinemias)". Endocrinol. Metab. Clin. North Am. 19 (2): 259–78. PMID 2192873.
- ^ Fredrickson, DS; Lees, RS (1965). "A system for phenotyping hyperlipoproteinemia" (PDF). Circulation 31 (3): 321–7. doi:10.1161/01.CIR.31.3.321. PMID 14262568.
- ^ Hyperlipoproteinemia, Type I from Centre for Arab Genomic Studies. Retrieved July 2011. Citing: "About 1:1,000,000 people are affected with Hyperlipoproteinemia type I worldwide with a higher prevalence in some regions of Canada."
- ^ a b Fung, M.; Hill, J.; Cook, D.; Frohlich, J. (2011). "Case series of type III hyperlipoproteinemia in children". Case Reports 2011: bcr0220113895. doi:10.1136/bcr.02.2011.3895.
- ^ a b Boman H,Hazzard WR, AlbersJJ, et ah Frequency of monogenic forms of hyperlipidemia in a normal population. AmJ ttum Genet 27:19A,1975. [1]
- ^ New Product Bulletin on Crestor® (rosuvastatin) [2]
- ^ OMIM entry 207750 last updated 02/10/2009
- ^ Yamamura, T.; Sudo, H.; Ishikawa, K.; Yamamoto, A. (1979). "Familial type I hyperlipoproteinemia caused by apolipoprotein C-II deficiency". Atherosclerosis 34 (1): 53–65. doi:10.1016/0021-9150(79)90106-0. PMID 227429. edit
- ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
- ^ OMIM entry 118830 updated 03/18/2004
- ^ thefreedictionary.com > hyperlipidemia Citing:
- Saunders Comprehensive Veterinary Dictionary, 3 ed. 2007 by Elsevier
- ^ Mattar M, Obeid O. Fish oil and the management of hypertriglyceridemia. Nutr Health. 2009;20(1):41-9.
- ^ Thompson, GR (2004). "Management of dyslipidaemia". Heart (British Cardiac Society) 90 (8): 949–55. doi:10.1136/hrt.2003.021287. PMC 1768388. PMID 15253984.
External links [edit]
- The Fredrickson papers (with photos from early lipoprotein research)
- 745209914 at GPnotebook
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Inborn error of lipid metabolism: dyslipidemia (E78, 272.0–272.6)
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| Hyperlipidemia |
- Hypercholesterolemia/Hypertriglyceridemia
- Lipoprotein lipase deficiency/Type Ia
- Familial apoprotein CII deficiency/Type Ib
- Familial hypercholesterolemia/Type IIa
- Combined hyperlipidemia/Type IIb
- Familial dysbetalipoproteinemia/Type III
- Familial hypertriglyceridemia/Type IV
- Xanthoma/Xanthomatosis
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| Hypolipoproteinemia |
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Hypoalphalipoproteinemia/HDL
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- Lecithin cholesterol acyltransferase deficiency
- Tangier disease
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Hypobetalipoproteinemia/LDL
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- Abetalipoproteinemia
- Apolipoprotein B deficiency
- Chylomicron retention disease
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| Lipodystrophy |
- Barraquer–Simons syndrome
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| Other |
- Lipomatosis
- Adiposis dolorosa
- Lipoid proteinosis
- APOA1 familial renal amyloidosis
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