Hyperlipidemia
Encyclopedia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia (British English) is the condition of abnormally elevated levels of any or all lipid
s and/or lipoprotein
s 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 apolipoprotein
s 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
.
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.
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.
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.
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%.
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
E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Its prevalence has been estimated to be approximately 1 in 10,000.
is an autosomal dominant condition occurring in approximately 1% of the population.
It is also associated with glucose intolerance and hyperuricemia
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.
Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food
s (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride level is markedly raised, fibrate
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
and rhabdomyolysis
and is therefore only done under close supervision. Other agents commonly added to statins are ezetimibe
, niacin
and bile acid sequestrant
s. 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
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s and/or lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
. It is the most common form of dyslipidemia
Dyslipidemia
Dyslipidemia or dyslipidaemia is an abnormal amount of lipids in the blood. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood, often due to diet and lifestyle. The prolonged elevation of insulin levels can lead to dyslipidemia...
(which also includes any decreased lipid levels).
Lipids (fat-soluble molecules) are transported in a protein
Apolipoprotein
Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....
capsule
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
, and the size of that capsule, or lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
, determines its density. The lipoprotein density and type of apolipoprotein
Apolipoprotein
Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....
s it contains determines the fate of the particle and its influence on metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
.
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
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
. Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a modifiable risk factor for cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
due to their influence on atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. In addition, some forms may predispose to acute pancreatitis
Acute pancreatitis
Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
.
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
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
, 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 . It can also lead to pancreatitis in excessive concentrations In medicine,...
or both in combined hyperlipidemia
Combined hyperlipidemia
In medicine, combined hyperlipidemia is a commonly occurring form of hypercholesterolemia characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL...
. Elevated levels of Lipoprotein(a)
Lipoprotein(a)
Lipoprotein is a lipoprotein subclass. Studies have identified Lp as a putative risk factor for atherosclerotic diseases such as coronary heart disease and stroke....
may also be classified as a form of hyperlipidemia.
Familial (primary)
Familial hyperlipidemias are classified according to the FredricksonDonald S. Fredrickson
Donald Sharp "Don" Fredrickson was an American medical researcher, principally of the lipid 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, also called cataphoresis, is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric field. This electrokinetic phenomenon was observed for the first time in 1807 by Reuss , who noticed that the application of a constant electric...
or ultracentrifugation
Ultracentrifuge
The ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as 2,000,000 g . There are two kinds of ultracentrifuges, the preparative and the analytical ultracentrifuge...
. 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. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO). It does not directly account for HDL
High density lipoprotein
High-density lipoprotein is one of the five major groups of lipoproteins, which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream...
, and it does not distinguish among the different genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
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)Lipoprotein lipase deficiencyLipoprotein lipase deficiency is caused by a mutation in the gene which codes lipoprotein lipase....
, due to a deficiency of lipoprotein lipaseLipoprotein lipaseLipoprotein lipase is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins , into two free...
(LPL) or altered apolipoprotein C2, resulting in elevated chylomicronChylomicronChylomicrons are lipoprotein particles that consist of triglycerides , phospholipids , cholesterol and proteins .They transport dietary lipids from the intestines to other locations in the body...
s, the particles that transfer fatty acids from the digestive tract to the liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. - Familial apoprotein CII deficiency (Type Ib), a condition caused by a lack of lipoprotein lipaseLipoprotein lipaseLipoprotein lipase is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins , into two free...
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 include 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
LDL receptor
The Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids 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 tissues. While it is unclear exactly what functional role APOB plays in LDL, it is the primary apolipoprotein component and is absolutely required for its formation...
gene (0.2%). The familial form is characterized by tendon xanthoma
Xanthoma
A xanthoma , from Greek xanthos, ξανθος, "yellow", is a deposition of yellowish cholesterol-rich material in tendons or other body parts in various disease states...
, xanthelasma
Xanthelasma
Xanthelasma is a sharply demarcated yellowish deposit 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)
- Lysosomal acid lipase deficiencyLysosomal Acid Lipase DeficiencyLysosomal Acid Lipase Deficiency happens when the body does not produce enough active LAL enzyme. Under normal conditions, the body produces an enzyme called lysosomal acid lipase . This enzyme plays an important role in breaking down fatty material in the body...
, often called (Cholesteryl ester storage diseaseCholesteryl ester storage diseaseCholesteryl Ester Storage Disease is the late onset phenotype for Lysosomal Acid Lipase Deficiency, a Lysosomal storage disease, which also has an early onset phenotype known as Wolman disease that primarily affects infants. CESD can present in childhood but often goes unrecognized until...
) - Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndromeMetabolic syndromeMetabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
, for which it is a diagnostic criterion)
Hyperlipoproteinemia type III
This form is due to high chylomicronChylomicron
Chylomicrons are lipoprotein particles that consist of triglycerides , phospholipids , cholesterol and proteins .They transport dietary lipids from the intestines to other locations in the body...
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 a class of apolipoprotein found in the chylomicron and IDLs that binds to a specific receptor on liver cells and peripheral cells. It is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.-Function:...
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 hypertriglyceridemiaFamilial hypertriglyceridemia
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population. Triglyceride levels, but not cholesterol, are elevated as a result of excess hepatic production of VLDL or heterozygous LPL deficiency. Unlike familial hypercholesterolemia, there is no...
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 atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
or, when associated with marked 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 . It can also lead to pancreatitis in excessive concentrations In medicine,...
, may lead to pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
and other complications of the chylomicronemia syndrome. The most common causes of acquired hyperlipidemia are:
- diabetes mellitusDiabetes mellitusDiabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
- Use of drugs such as diuretics, beta blockers, and estrogens
Other conditions leading to acquired hyperlipidemia include:
- Hypothyroidism
- renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
- nephrotic syndromeNephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
- alcoholAlcoholic beverageAn alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
- Some rare endocrine disorders and metabolic disorders
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
Management
For treatment of type II, dietary modification is the initial approach but many patients require treatment with statinStatin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
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 amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia , and are therefore hypolipidemic agents.- Members :...
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. "Myopathy" simply means muscle disease...
and rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
and is therefore only done under close supervision. Other agents commonly added to statins are ezetimibe
Ezetimibe
Ezetimibe is a drug that lowers cholesterol. It acts by decreasing cholesterol absorption in the intestine. It may be used alone , when other cholesterol-lowering medications are not tolerated, or together with statins when statins alone do not control cholesterol.Even though ezetimibe decreases...
, niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
and bile acid sequestrant
Bile acid sequestrant
The bile acid sequestrants are a group of medications used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic...
s. 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
Omega-3 fatty acid
N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....