| 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) is the condition of 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, 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.
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.
Contents |
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 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 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.
| 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 | 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 | ||||
Type I hyperlipoproteinemia exists in several forms:
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, 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.
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.
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%.
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]
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.[6]
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
Non-classified forms are extremely rare:
Acquired hyperlipidemias (also called secondary dyslipoproteinemias) may 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:
Other conditions leading to acquired hyperlipidemia include:
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[12]
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]