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 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, 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 caused by specific genetic abnormalities, or acquired 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 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. 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, due to a deficiency
of lipoprotein lipase 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, a condition caused by a lack of lipoprotein lipase activator.
Chylomicronemia due to circulating inhibitor of lipoprotein lipase
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, polygenic, or truly familial as a result of a mutation either
in the LDL receptor gene on chromosome 19 or the ApoB gene. 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 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,
tendon and tuberous xanthomas, Arcus juvenilis, 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 Lysosomal acid lipase deficiency, often called
Secondary combined hyperlipoproteinemia Hyperlipoproteinemia type III
This form is due to high chylomicrons and IDL. 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. Its prevalence has been estimated to be approximately 1 in 10,000.
It is associated with hypercholesterolaemia, hypertriglyceridaemia, a normal ApoB concentration,
and two types of skin signs. 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 is a commonly occurring form of hypercholesterolemia
characterised by increased LDL and triglyceride concentrations, often accompanied by decreased
HDL. On lipoprotein electrophoresis 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 are generally
due to an increase in VLDL, a class of lipoprotein that is prone to cause atherosclerosis.
Types Familial combined hyperlipidemia 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. 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, specifically PPARα, to decrease free fatty acid production. Statin drugs,
especially the synthetic statins 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
Acquired hyperlipidemias 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 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 statins 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.
See also List of xanthoma variants associated with
hyperlipoproteinemia subtypes Combined hyperlipidemia
References
External links The Fredrickson papers
745209914 at GPnotebook