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Hyperlipidemia
 
 
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Hyperlipidemia, hyperlipoproteinemia or dyslipidemia is the presence of raised or abnormal levels of lipid
Lipid

Lipids are broadly defined as any fat-soluble , naturally-occurring molecule, such as fats, oils, waxes, cholesterol, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others....
s and/or lipoprotein
Lipoprotein

A lipoprotein is a biochemistry assembly that contains both proteins and lipids. The lipids or their derivatives may be covalently or non-covalently bound to the proteins....
s in the blood
Blood

Blood is a specialized bodily fluid that delivers necessary substances to the body's Cell s ? such as nutrients and oxygen ? and transports waste products away from those same cells....
. Lipids (fatty molecules) are transported in a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence on metabolism
Metabolism

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments....
.

Lipid and lipoprotein abnormalities are extremely common in the general population, and are regarded as a highly modifiable risk factor for cardiovascular disease
Cardiovascular disease

Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the Circulatory system , it is usually used to refer to those related to atherosclerosis ....
 due to the influence of cholesterol
Cholesterol

Cholesterol is a lipidic, waxy alcohol found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes where it is required to establish proper membrane permeability and membrane fluidity....
, one of the most clinically relevant lipid substances, on atherosclerosis
Atherosclerosis

Atherosclerosis is a syndrome affecting artery blood vessels. It is a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low density lipoproteins without adequate removal of fats and cholesterol from the macrophages by functional high density lipoprot...
.






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Hyperlipidemia, hyperlipoproteinemia or dyslipidemia is the presence of raised or abnormal levels of lipid
Lipid

Lipids are broadly defined as any fat-soluble , naturally-occurring molecule, such as fats, oils, waxes, cholesterol, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others....
s and/or lipoprotein
Lipoprotein

A lipoprotein is a biochemistry assembly that contains both proteins and lipids. The lipids or their derivatives may be covalently or non-covalently bound to the proteins....
s in the blood
Blood

Blood is a specialized bodily fluid that delivers necessary substances to the body's Cell s ? such as nutrients and oxygen ? and transports waste products away from those same cells....
. Lipids (fatty molecules) are transported in a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence on metabolism
Metabolism

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments....
.

Lipid and lipoprotein abnormalities are extremely common in the general population, and are regarded as a highly modifiable risk factor for cardiovascular disease
Cardiovascular disease

Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the Circulatory system , it is usually used to refer to those related to atherosclerosis ....
 due to the influence of cholesterol
Cholesterol

Cholesterol is a lipidic, waxy alcohol found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes where it is required to establish proper membrane permeability and membrane fluidity....
, one of the most clinically relevant lipid substances, on atherosclerosis
Atherosclerosis

Atherosclerosis is a syndrome affecting artery blood vessels. It is a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low density lipoproteins without adequate removal of fats and cholesterol from the macrophages by functional high density lipoprot...
. In addition, some forms may predispose to acute pancreatitis
Acute pancreatitis

Acute pancreatitis is a sudden inflammation of the pancreas. Depending on its severity, it can have severe complications and high mortality despite treatment....
.

Classification

Hyperlipidemias are classified according to the Fredrickson
Donald S. Fredrickson

Donald Sharp "Don" Fredrickson was an United States medical research, principally of the lipid metabolism and cholesterol metabolism, and director of National Institutes of Health and subsequently the Howard Hughes Medical Institute....
 classification which is based on the pattern of lipoproteins on electrophoresis
Electrophoresis

Electrophoresis is the best-known electrokinetic phenomena. It was discovered by Reuss in 1807. He observed that clay particles dispersed in water migrate under influence of an applied electric field....
 or ultracentrifugation
Ultracentrifuge

The ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as 1,000,000 g ....
. It was later adopted by the World Health Organization
World Health Organization

The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health....
 (WHO). It does not directly account for HDL
High density lipoprotein

High-density lipoproteins is one of the 5 major groups of lipoproteins which enable lipids like cholesterol and triglycerides to be transported within the water based blood stream....
, and it does not distinguish among the different genes
Gênes

G?nes is the name of a d?partement in France of the First French Empire in present Italy. It was named after the city Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa....
 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

This very rare form (also known as Buerger-Gruetz syndrome, primary hyperlipoproteinaemia, or familial hyperchylomicronemia) is due to a deficiency of lipoprotein lipase
Lipoprotein lipase

Lipoprotein lipase is an enzyme that hydrolyzes lipids in lipoproteins, such as those found in chylomicrons and very low density lipoproteins , into three free fatty acids and one glycerol molecule....
 (LPL) or altered apolipoprotein C2
Apolipoprotein C2

Apolipoprotein C2 is an apolipoprotein responsible for the activation of lipoprotein lipase in capillaries and thus begins the catabolism of the chylomicrons and VLDL....
, resulting in elevated chylomicron
Chylomicron

Chylomicrons are large lipoprotein that transport dietary lipids from the intestines to other locations in the body. Chylomicrons are one of the 5 major groups of lipoproteins which enable fats and cholesterol to move within the water based solution of the blood stream....
s, the particles that transfer fatty acids from the digestive tract to the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
. 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.

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
LDL receptor

The Low-Density Lipoprotein Receptor is a mosaic protein that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles....
 gene on chromosome 19 (0.2% of the population) or the ApoB
Apolipoprotein B

Apolipoprotein B is the primary apolipoprotein of low-density lipoproteins , which is responsible for carrying cholesterol to Biological tissues....
 gene (0.2%). The familial form is characterized by tendon xanthoma
Xanthoma

A xanthoma is a deposition of yellowish cholesterol-rich material in tendons and other body parts in various disease states:* Tendon xanthomas ...
, xanthelasma
Xanthelasma

Xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. Although not harmful or painful, these minor growths may be disfiguring and can be removed....
 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)
  • Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome
    Metabolic syndrome

    Metabolic syndrome is a combination of medicine disorders that increase the risk of developing cardiovascular disease and Diabetes mellitus. It affects one in five people, and prevalence increases with age....
    , for which it is a diagnostic criterion)


Treatment
While dietary modification is the initial approach, many patients require treatment with statin
Statin

The statins are a class of drugs that lower cholesterol levels in people with or at risk of cardiovascular disease.They lower cholesterol by inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting step enzyme of the mevalonate pathway of cholesterol synthesis....
s (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride level is markedly raised, fibrate
Fibrate

In pharmacology, the fibrates are a class of Amphiphile carboxylic acids. They are used for a range of metabolism disorders, mainly hypercholesterolemia , and are therefore hypolipidemic agents....
s may be preferable due to their beneficial effects. Combination treatment of statins and fibrates, while highly effective, causes a markedly increased risk of myopathy
Myopathy

In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness....
 and rhabdomyolysis
Rhabdomyolysis

Rhabdomyolysis is the rapid breakdown of skeletal muscle tissue due to injury to muscle tissue. The muscle damage may be caused by physical , chemical, or biological factors....
 and is therefore only done under close supervision. Other agents commonly added to statins are ezetimibe
Ezetimibe

Ezetimibe is an anti-hyperlipidemic medication which is used to lower cholesterol levels. It acts by decreasing cholesterol absorption in the intestine....
, niacin
Niacin

Niacin, also known as vitamin B3, is a water-soluble vitamin which prevents the Nutrition disorder pellagra. It is an organic compound with the chemical formula C6H5NO2....
 and bile acid sequestrant
Bile acid sequestrant

The bile acid sequestrants are a group of medications used for binding certain components of bile in the gut. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut....
s. There is some evidence for benefit of plant sterol-containing products and ?3-fatty acids
Omega-3 fatty acid

n-3 fatty acids are a family of unsaturated fat fatty acids that have in common a final carbon?carbon double bond#Bond order in the essential fatty acid#Nomenclature and terminology position; that is, the third bond from the methyl end of the fatty acid....


Hyperlipoproteinemia type III

This form is due to high chylomicron
Chylomicron

Chylomicrons are large lipoprotein that transport dietary lipids from the intestines to other locations in the body. Chylomicrons are one of the 5 major groups of lipoproteins which enable fats and cholesterol to move within the water based solution of the blood stream....
s 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
Apolipoprotein E

Apolipoprotein E is an apolipoprotein found in the chylomicron and intermediate density lipoproteins that binds to a specific Receptor on hepatocytes and peripheral cells....
 E2/E2 genotype. It is due to cholesterol-rich VLDL (ß-VLDL). Prevalence is 0.02% of the population.

Hyperlipoproteinemia type IV (type 4 = familial)

This form is due to high triglyceride
Triglyceride

is a glyceride in which the glycerol is esterified with three fatty acids. It is the main constituent of vegetable oil and animal fats....
s. It is also known as hypertriglyceridemia
Hypertriglyceridemia

In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia ....
 (or pure hypertriglyceridemia). According to the NCEP-ATPIII definition of high triglycerides (>200 mg/dl), prevalence is about 16% of adult population.

Hyperlipoproteinemia type V (type 5 = endogenous)

This type is very similar to type I, but with high VLDL in addition to chylomicrons.

It is also associated with glucose intolerance and hyperuricemia

Unclassified forms

Non-classified forms are extremely rare:
  • Hypo-alpha lipoproteinemia
  • Hypo-beta lipoproteinemia (prevalence 0.01-0.1%)


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