Hyperlipidemia

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.

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.

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.



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), a condition caused by a lack of lipoprotein lipase activator.
 * Chylomicronemia due to circulating inhibitor of lipoprotein lipase (Type Ic)

Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications in clude retinal vein occlusion, acute pancreatitis, steatosis and organomegaly, and lipaemia retinalis.

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
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)
 * 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.

Hyperlipoproteinemia type IV
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.

Hyperlipoproteinemia type V
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
Non-classified forms are extremely rare:
 * Hyperalphalipoproteinemia
 * Polygenic hypercholesterolemia

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: 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.
 * diabetes mellitus
 * Use of drugs such as diuretics, beta blockers, and estrogens
 * Hypothyroidism
 * renal failure
 * nephrotic syndrome
 * alcohol
 * Some rare endocrine disorders and metabolic disorders

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