DiseasesDB = 6255
MeshID = D006949
Hyperlipidemia, hyperlipoproteinemia or dyslipidemia is the presence of raised or abnormal levels of
lipids and/or lipoproteins in the blood. Lipids (fatty molecules) are transported in a proteincapsule, and the density of the lipids and type of protein determines the fate of the particle and its influence on metabolism.
Lipid and lipoprotein abnormalities are extremely common in the general population, and are regarded as a highly modifiable risk factor for
cardiovascular diseasedue to the influence of cholesterol, one of the most clinically relevant lipid substances, on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.
Hyperlipidemias are classified according to the Fredrickson classification which is based on the pattern of lipoproteins on
electrophoresisor ultracentrifugation. [Frederickson DS, Lee RS. A system for phenotyping hyperlipidemia. "Circulation" 1965;31:321-7. PMID 14262568.] 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 genesthat may be partially responsible for some of these conditions. It remains a popular system of classification, but is considered dated by many.
Hyperlipoproteinemia type I
This very rare form (also known as "Buerger-Gruetz syndrome", "primary hyperlipoproteinaemia", or "familial hyperchylomicronemia") is 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 tractto the liver. Lipoprotein lipase is also responsible for the initial breakdown of endogenously made triacylglycerides in the form of very low density lipoprotein (VLDL). As such, one would expect a defect in LPL to also result in elevated VLDL. Its prevalence is 0.1% of the population.
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.
This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the
LDL receptorgene on chromosome 19(0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasmaand 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%.
* Familial combined hyperlipoproteinemia (FCH)
* Secondary combined hyperlipoproteinemia (usually in the context of
metabolic syndrome, for which it is a diagnostic criterion)
While dietary modification is the initial approach, 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 myopathyand rhabdomyolysisand is therefore only done under close supervision. Other agents commonly added to statins are ezetimibe, niacinand bile acid sequestrants. There is some evidence for benefit of plant sterol-containing products and ω3-fatty acids [Thompson GR. Management of dyslipidaemia. "Heart" 2004;90:949-55. PMID 15253984.]
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 (type 4 = familial)=
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. [Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. "Circulation" 2002; 106; page 3240]
=Hyperlipoproteinemia type V (type 5 = endogenous)=
This type is very similar to type I, but with high
VLDLin addition to chylomicrons.
It is also associated with glucose intolerance and hyperuricemia
Non-classified forms are extremely rare:
* Hypo-alpha lipoproteinemia
* Hypo-beta lipoproteinemia (prevalence 0.01-0.1%)
* [http://profiles.nlm.nih.gov/FF/Views/Exhibit/visuals/scientist.html The Fredrickson papers (with photos from early lipoprotein research)]
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