| Hyperlipidemia |
| Synonyms |
hyperlipoproteinemia, hyperlipidaemia |
|
| A 4-ml sample of hyperlipidemic blood in a vacutainer with EDTA. Left to settle for four hours without centrifugation, the lipids separated into the top fraction. |
| Classification and external resources |
| Specialty |
Cardiology |
| ICD-10 |
E78 |
| ICD-9-CM |
272.0-272.4 |
| DiseasesDB |
6255 |
| Patient UK |
Hyperlipidemia |
| MeSH |
D006949 |
|
[edit on Wikidata]
|
Hyperlipidemia is abnormally elevated levels of any or all lipids and/or lipoproteins in the blood.[1] It is the most common form of dyslipidemia (which includes any abnormal lipid levels).
Lipids (water-insoluble 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 into 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 modifiable risk factors for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.
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 Screening
- 3 Management
- 4 See also
- 5 References
- 6 External links
Classification
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 a 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)
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.
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 |
Acute pancreatitis, lipemia retinalis, eruptive skin xanthomas, hepatosplenomegaly |
Diet control |
Creamy top layer |
One 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 |
One in 500 for heterozygotes |
| b |
144250 |
Familial combined hyperlipidemia |
Decreased LDL receptor and increased ApoB |
LDL and VLDL |
|
Statins, niacin, fibrate |
Turbid |
1 in 100 |
| Type III |
107741 |
Familial dysbetalipoproteinemia |
Defect in Apo E 2 synthesis |
IDL |
Tuboeruptive xanthomas and palmar xanthomas |
Fibrate, statins |
Turbid |
One 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 |
One in 100 |
| Type V |
144650 |
|
Increased VLDL production and decreased LPL |
VLDL and chylomicrons |
|
Niacin, fibrate |
Creamy top layer and turbid bottom |
|
Relative prevalence of familial forms of hyperlipoproteinemia
[6]
Hyperlipoproteinemia type I
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),[7][8] a condition caused by a lack of lipoprotein lipase activator.[9]:533
- Chylomicronemia due to circulating inhibitor of lipoprotein lipase (type Ic)[10]
Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis, and organomegaly, and lipemia retinalis.
Hyperlipoproteinemia type II
Hyperlipoproteinemia type II, by far the most common form, is further classified into types IIa and IIb, depending mainly on whether elevation in the triglyceride level occurs 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 one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.
HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in the blood due to the lack of uptake (no Apo B receptors) of LDL particles. This pathology, however, is the second-most common disorder of the various hyperlipoproteinemias, with individuals with a heterozygotic predisposition of one in every 500 and individuals with homozygotic predisposition of one in every million. These individuals may present with a unique set of physical characteristics such as xanthelasmas (yellow deposits of fat underneath the skin often presenting in the nasal portion of the eye), tendon and tuberous xanthomas, arcus juvenilis (the graying of the eye often characterized in older individuals), arterial bruits, claudication, and of course atherosclerosis. Laboratory findings for these individuals are obvious and yet interesting because their serum cholesterol levels are two to three times greater than normal, as well as increased LDL cholesterol, but their triglycerides and VLDL values fall in the normal ranges. To manage persons with HLPIIa, drastic measures may need to be taken, especially if their HDL cholesterol levels are less than 30 mg/dL and their LDL levels are greater than 160 mg/dL. A proper diet for these individuals requires a decrease in total fat to less than 30% of total calories with a ratio of monounsaturated:polyunsaturated:saturated fat of 1:1:1. Cholesterol should be reduced to less than 300 mg/day, thus the avoidance of animal products and to increase fiber intake to more than 20 g/day with 6g of soluble fiber/day.[citation needed] Exercise should be promoted, as it can increase HDL. The overall prognosis for these individuals is in the worst-case scenario if uncontrolled and untreated individuals may die before the age of 20, but if one seeks a prudent diet with correct medical intervention, the individual may see an increased incidence of xanthomas with each decade, and Achilles tendinitis and accelerated atherosclerosis will occur.
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)
- 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
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]
It is associated with hypercholesterolemia (typically 8-12 mmol/L), hypertriglyceridemia (typically 5-20 mmol/L), a normal ApoB concentration, and two types of skin signs (palmar xanthomata or orange discoloration of skin creases, and tuberoeruptive xanthomata on the elbows and knees). It is characterized by the early onset of cardiovascular disease and peripheral vascular disease. Remnant hyperlipidemia occurs as a result of abnormal function of the ApoE receptor, which is normally required for clearance of chylomicron remnants and IDL from the circulation. The receptor defect causes levels of chylomicron remnants and IDL to be higher than normal in the blood stream. The receptor defect is an autosomal recessive mutation or polymorphism.
Hyperlipoproteinemia type IV
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.[11]
This form is due to high triglyceride level. Other lipoprotein levels are normal or increased a little.
Treatment include diet control, fibrates and niacins. Statins are not better than fibrates when lowering triglyceride levels.
Hyperlipoproteinemia type V
Hyperlipoproteinemia type V, also known as mixed hyperlipoproteinemia familial or mixed hyperlipidemia,[12] is very similar to type I, but with high VLDL in addition to chylomicrons.
It is also associated with glucose intolerance and hyperuricemia.
In medicine, combined hyperlipidemia (or -aemia) (also known as "multiple-type hyperlipoproteinemia") is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterized by increased LDL and triglyceride concentrations, often accompanied by decreased HDL.[13] On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most common inherited lipid disorder, occurring in about one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 has this disorder. The elevated triglyceride levels (>5 mmol/l) are generally due to an increase in very low density lipoprotein (VLDL), a class of lipoprotein prone to cause atherosclerosis.
Types
- Familial combined hyperlipidemia (FCH) is the familial occurrence of this disorder, probably caused by decreased LDL receptor and increased ApoB.
- FCH is extremely common in patients who suffer from other diseases from the metabolic syndrome ("syndrome X", incorporating diabetes mellitus type II, hypertension, central obesity and CH). Excessive free fatty acid production by various tissues leads to increased VLDL synthesis by the liver. Initially, most VLDL is converted into LDL until this mechanism is saturated, after which VLDL levels elevate.
Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.
Unclassified familial forms
These unclassified forms are extremely rare:
- Hyperalphalipoproteinemia
- Polygenic hypercholesterolemia
Acquired (secondary)
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 thiazide diuretics,[2] beta blockers,[2] and estrogens[2]
Other conditions leading to acquired hyperlipidemia include:
- Hypothyroidism[2]
- Kidney failure[2]
- Nephrotic syndrome[2]
- Alcohol consumption[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.[13][14]
Screening
Testing the general population under the age of 40 without symptoms is of unclear benefit.[15][16]
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 (peroxisome proliferator-activated receptor-alpha agonists) 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, so is 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.[17] Some evidence exists for benefit of plant sterol-containing products and omega-3 fatty acids.[18]
See also
- List of xanthoma variants associated with hyperlipoproteinemia subtypes
- Combined hyperlipidemia
References
- ^ 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.
- ^ New Product Bulletin on Crestor® (rosuvastatin)
- ^ 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.
- ^ 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
- ^ Boman H, Hazzard WR, AlbersJJ, et ah Frequency of monogenic forms of hyperlipidemia in a normal population. AmJ ttum Genet 27:19A,1975. [1]
- ^ "Medical Definition Search For 'Type 5 Hyperlipidemia". medilexicon. Retrieved 1 November 2013.
- ^ a b thefreedictionary.com > hyperlipidemia Citing:
- Saunders Comprehensive Veterinary Dictionary, 3 ed. 2007 by Elsevier
- ^ Sameer Ansar; Juraj Koska; Peter D Reaven. "Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: Role of Incretins". Cardiovascular Diabetology
- ^ "Screening for Dyslipidemia in Younger Adults: A Systematic Review for the U.S. Preventive Services Task Force". Annals of Internal Medicine. 9 August 2016. doi:10.7326/M16-0946.
- ^ "Screening for Lipid Disorders in Children and Adolescents". JAMA. August 9, 2016. doi:10.1001/jama.2016.9852.
- ^ 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
- 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)
|
|
| 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 |
| Hypoalphalipoproteinemia/HDL |
- Lecithin cholesterol acyltransferase deficiency
- Tangier disease
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| Hypobetalipoproteinemia/LDL |
- Abetalipoproteinemia
- Apolipoprotein B deficiency
- Chylomicron retention disease
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|
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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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