Hyperlipidemia Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia
involves abnormally elevated levels of any or all lipids and/or lipoproteins in the blood.
It is the most common form of dyslipidemia .
Lipids (fat-soluble molecules) are transported in a protein capsule. 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 into 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 are also classified according to 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.
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.:533
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 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.
HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in
the blood due to the lack of uptake (no Apo B receptors) of LDL particles. This pathology
however is the second most common disorder of the various hyperlipoproteinemias, with
individuals with a heterozygotic predisposition of 1 in every 500 and individuals with homozygotic
predisposition of 1 in every million. These individuals may present with a very unique
set of physical characteristics such as: Xanthelasma’s (yellow deposits of fat underneath the skin
often presenting in the nasal portion of the eye), tendon and tuberous xanthomas, Arcus
juvenilis (the graying of the eye often characterized in older individuals), Arterial bruits, claudication,
and of course atherosclerosis. Lab findings for these individuals are obvious and yet
interesting in the fact that their Serum cholesterol is 2-3 times greater than normal as well as
increased LDL cholesterol but their triglycerides and VLDL values fall in the normal ranges.
To manage person’s with HLPIIa drastic measures may need to be taken especially if their HDL
cholesterol is less than 30 mg/dl and their LDL cholesterol is greater than 160 mg/dl.
A proper diet for these individuals requires a decrease in total fat to less than 30% of
total calories with a ratio of mon:poly:saturated fat of 1:1:1. Cholesterol should be reduced
to less than 300 mg/day thus the avoidance of animal products and to increase fiber intake
to more than 20g/day with 6g of soluble fiber/day. Of course exercise should be promoted as exercise
can increase HDL. The overall prognosis for these individuals is in the worst case scenario
if uncontrolled and untreated individuals may die before the age of 20, however if one
seeks a prudent diet with correct medical intervention the individual my see an increased
incidence of xanthomas with each decade, Achilles tendinitis will occur, and accelerated atherosclerosis.
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. It is associated with hypercholesterolaemia
(typically 8-12 mmol/L), hypertriglyceridaemia (typically 5-20 mmol/L), a normal ApoB concentration,
and two types of skin signs (palmar xanthomata or orange discoloration of skin creases, and
tuberoeruptive xanthomata on the elbows and knees). It is characterized by the early onset
of cardiovascular disease and peripheral vascular disease. Remnant hyperlipidaemia occurs as
a result of abnormal function of the ApoE receptor, which is normally required for clearance
of chylomicron remnants and IDL from the circulation. The receptor defect causes levels of chylomicron
remnants and IDL to be higher than normal in the blood stream. The receptor defect is
an autosomal recessive mutation or polymorphism. Hyperlipoproteinemia type IV
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately
1% of the population. Hyperlipoproteinemia type V
Hyperlipoproteinemia type V,also known as mixed hyperlipoproteinemia familial or mixed
hyperlipidemia, is very similar to type I, but with high VLDL in addition to chylomicrons.
It is also associated with glucose intolerance and hyperuricemia
In medicine, combined hyperlipidemia (or -aemia) (also known as "Multiple-type hyperlipoproteinemia")
is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterised
by increased LDL and triglyceride concentrations, often accompanied by decreased HDL.:534 On
lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia
type IIB. It is the most common inherited lipid disorder, occurring in approximately
one in two hundred persons. In fact, almost one in five individuals who develop coronary
heart disease before the age of sixty will have this disorder. The elevated triglyceride
levels (greater than 5 mmol/l) are generally due to an increase in VLDL (very low density
lipoprotein), a class of lipoprotein that is prone to cause atherosclerosis.
Types Familial combined hyperlipidemia (FCH) is
the familial occurrence of this disorder, probably caused by decreased LDL receptor
and increased ApoB. Acquired combined hyperlipidemia is extremely
common in patients who suffer from other diseases from the metabolic syndrome ("syndrome X",
incorporating diabetes mellitus type II, hypertension, central obesity and CH). Excessive free fatty
acid production by various tissues leads to increased VLDL synthesis by the liver. Initially,
most VLDL is converted into LDL until this mechanism is saturated, after which VLDL levels
elevate. Both conditions are treated with fibrate drugs,
which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to
decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin
and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due
to increased LDL-receptor expression. Unclassified familial forms
Non-classified forms are extremely rare: Hyperalphalipoproteinemia
Polygenic hypercholesterolemia Acquired (secondary)
Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often 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: diabetes mellitus
Use of drugs such as diuretics, beta blockers, and estrogens
Other conditions leading to acquired hyperlipidemia include:
Hypothyroidism renal failure
nephrotic syndrome alcohol usage
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 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
For the other types see the treatment column in the Fredrickson classification table above.
Patient Empowerment In 2013, LPLD Connect launched for people
with Hyperlipoproteinemia type 1, Chylomicronemia syndrome, Lipoprotein lipase deficiency to
share de-identified information and learn from others LPLDConnect.