LipidProfile

Lab Notes (6)

LipidProfile
Contents
Total -1
Cholesterol
Triglycerides-2
HDL Cholesterol-3
LDL Cholesterol-4
Apolipoproteins -5
A-1, A-ll , B, C-11,
C-lll and E
Lipoprotein (a)-6

The lipid profile is a group of tests comprising

triglycerides, total cholesterol, HDLand LDL
cholesterol.
The lipid profile is used, together with other risk
factors, to assess a person's risk of cardiovascular
.disease
Dietary fat is digested in the stomach and small
intestine and broken down into lipids (triglycerides
and
cholesterol). These are insoluble in the blood stream
and are therefore packaged into a structure with
phospholipids and apoproteins to form lipoproteins.
Lipoproteins are classified by their density (size)
into Chylomicrons, very low density lipoproteins
(VLDL),
low density lipoproteins (LDL) and high density
lipoproteins (HDL)
LDL cholesterol is the so-called (bad cholesterol) as
it
transports cholesterol to the cells for utilisation,
whereas HDL transports cholesterol from the cells to
the liver for metabolism and elimination. Therefore
.HDL is the(good cholesterol)
LDL cholesterol is involved in atherogenesis (lipid
deposits in the coronary arteries) in cardiovascular
disease (CVD), which is one of the main risk factors
.for myocardial infarction
It is very important to get the balance between the
protective HDL and the destructive LDL right in
order to
reduce the risk of CVD. This can be achieved either
through dietary and lifestyle changes or treatment
.with cholesterol reducing drugs called statins

Lipid Profile

Regular check-ups are necessary to establish risk

Total cholesterol
.and, if necessary, monitor treatment

Total cholesterol measures cholesterol in all lipoprotein

sub- classes to assess a patient's cholesterol levels.
Because it includes both 'good' HDL and 'bad' LDL, total
cholesterol measurement alone cannot accurately predict
CVD risk.
Total cholesterol is useful as an initial screen but elevated
levels suggest a lipid profile is required
Sample type Serum and EDTA or heparinised plasma

Triglycerides
Triglycerides are the main component of animal fats and
vegetable oils.
They consist of fatty acids linked to a glycerol backbone.
High triglyceride levels increase the atherogenicity of HDL
and LDL.

Triglyceride levels are elevated immediately after a meal

and high levels can dramatically affect the accuracy of
HDL and LDL
Sample type Serum and EDTA or heparinised plasma

HDL and LDL Cholesterol

HDL cholesterol
High-density lipoprotein, or HDL, carries about 30%
.of the cholesterol in blood
The cholesterol carried by High Density Lipoproteins is
described as 'good cholesterol' since HDL transports
cholesterol from the tissues to the liver for removal from
the body.
HDL is a negative risk factor for CVD: its i inversely
.related to CVD risk

LDL cholesterol
Low-density lipoprotein, or LDL, carries about 65%
.of the cholesterol in blood
The cholesterol carried by Low Density Lipoproteins is
described as 'bad cholesterol' since LDL transports
cholesterol to the tissues and is linked to the development
of
atherosclerotic lesions.
Lowering LDL levels is the principal target of
Cardiovascular disease (CVD) therapy.
Accurate LDL measurement is vital to establish CVD risk
and to determine whether patients are achieving their LDL
.targets through therapy
Many laboratories still calculate LDL using the Friedewald
equation:
LDL = TC - HDL VLDL (VLDL is calculated from triglycerides)

The VLDL calculation assumes that most of the circulating

triglycerides are contained within VLDL and that the ratio
between cholesterol and triglycerides in VLDL is constant.
This
assumption is not always correct.

HDL and LDL Cholesterol

For example as triglyceride levels rise, triglycerides are

transferred to HDL and LDL leading to a growing
discrepancy between the calculated LDL and the true
value

Cholesterol
is a soft, fat-like substance found in the
bloodstream and in all your body's cells. Your body
makes all the cholesterol it needs.
Low-density lipoprotein (LDL or 'bad') cholesterol
can join with fats and other substances to build up
in the inner walls of your arteries.
The arteries can become clogged and narrow, and
blood flow is reduced.
High-density lipoprotein (HDL or 'good') carries
harmful cholesterol away from the arteries and
helps protect you from heart attack and stroke.

HDL and LDL Cholesterol

HDL and LDL Cholesterol

Direct LDL vs. calculated LDL
Calculated LDL was originally introduced to measure LDL
because no simple direct LDL assay was available
There are several reasons to use a direct LDL assay
instead of calculated LDL:
1. Direct methods do not require a fasting sample.
2. Calculated LDL is inherently variable since it is based on
three assays and a calculation.
3. Calculated LDL has known limitations for example in
patients with diabetes, liver disease or high triglyceride
levels as shown in the graph.
The higher the level of LDL cholesterol in your blood, the
GREATER your chance is of getting heart disease. The
higher the level of HDL cholesterol in your blood, the
LOWER your chance is of getting heart disease

Lipoproteins
About lipoproteins
Lipoproteins are lipid-protein complexes that transport
cholesterol and triglycerides in the bloodstream.
They are HDL, LDL, VLDL and chylomicrons.
The lipoproteins have similar structures but are different
sizes, densities and compositions.
They exist in a state of dynamic equilibrium, transferring
cholesterol and triglycerides between each other.
Individual lipoproteins can change size and density or be
converted into other lipoproteins
Relative lipoprotein sizes
1 Chylomicron
2 VLDL (Very Low Density Lipoprotein)
3 LDL (Low Density Lipoprotein)

4 HDL (High Density Lipoprotein)

3
4
Lipoprotein structure

Cholesterol Ester
45%
Phospholipids 20%
Free Cholesterol
7.5%

Emerging Risk Factors

Triglycerides 7.5%
Apolipoprotein 20%

Small dense (sd) LDL Cholesterol

LDL cholesterol is considered the most atherogenic
component of cholesterol constituting a major risk factor
for
cardiovascular disease (CVD).
There are two main types of LDL which differ in terms of
size, density and composition; large buoyant LDL and
small dense LDL.
Small dense LDL Cholesterol (sLDL) penetrates the
arterial wall more readily, has a lower binding affinity for
the LDL
receptor and a longer plasma half life making it more
atherogenic than the larger LDL subtype.
Research has shown individuals with a predominance of
sLDL have a 3-fold increased risk of myocardial infarction.
Determination of sLDL allows the clinician to get a more
comprehensive picture of lipid risk factors and tailor
treatment accordingly.
Measurements are useful in cases of;

Coronary or peripheral arterial disease

Hyper/Dyslipidemia
Hypertension
Diabetes

A p o li p o p r o t e i n s
Why measure apolipoproteins?
Apolipoproteins and the ratio between them are useful in
the assessment of cardiovascular risk.
They have particular value in monitoring lipid lowering
therapies where HDL-C and LDL-C alone are less predictive
of future cardiovascular events.
Clinical significance
1- Apolipoproteins A-I and A-II
The main role of Apolipoprotein A-I (Apo A-I) is in the
removal of excess cholesterol from extra-hepatic tissues.
Like HDL Cholesterol Apo A-I can be described as nonatherogenic showing an inverse relationship to
cardiovascular disease risk.
Individuals with cardiovascular disease generally have
reduced levels of Apo A-I and increased levels of Apo B.
Apolipoprotein A-II (APO A-II) is a major constituent of
HDL
cholesterol and plays an important role in reverse
cholesterol

transport and lipid metabolism.

The distribution of Apo A-I within the HDL particle is
primarily determined by the production rate of Apo A-II.
Increased production of Apo A-II promotes atherosclerosis
by
decreasing the proportion of anti-atherogenic HDL
containing Apo A-I.
2- Apolipoprotein B
Apolipoprotein B (Apo B) is the main protein in LDL
Cholesterol and is the ligand concerned with the uptake of
cholesterol.
Apo B is a component of LDL cholesterol and enables
tissue cells to take up cholesterol.

A p o li p o p r o t e i n s

Elevated levels of Apo B indicate increased cardiovascular

risk even when total and LDL cholesterol levels are within
the normal range.
3- Apolipoproteins C-II and C-III
Apolipoprotein C-II (APO C-II) acts as a co-factor for
lipoprotein lipase, an enzyme that breaks down
lipoproteins and hydrolyses triglycerides in chylomicrons
and VLDL for absorption into tissue cells.
Apo C-II deficiency has been linked with
hypertriglyceridemia
Apolipoprotein C- III (Apo C-III) circulates in the plasma in
association with triglyceride rich lipoproteins
(chylomicrons, VLDL and IDL) and HDL.
Apo C-III modulates the uptake of triglyceride-rich
lipoproteins by the LDL receptor related protein through
inhibition of lipoprotein lipase.
Elevated levels of Apo C-III are associated with both
primary

and secondary hypertriglyceridemia.

Genetically determined Apo C-III deficiency in humans has
shown to increase the rate of triglyceride clearance from
the
plasma by 6 to 7-fold.
Apo C-III levels have been reported higher in many
pathological conditions including Type 2 diabetes,
hyperbilirubinemia, kidney deficiency and decreased
thyroid function

A p o li p o p r o t e i n s
4-Apolipoprotein E
There are three similar isoforms of Apo E: Apo E2, E3, and
E4 with E3 being the most common.
Apo E has a variety of functions depending on the
lipoprotein.
Apo E deficiency gives rise to high cholesterol and
triglyceride levels, promoting atherosclerosis.
The polymorphism has been associated with diseases
other than cardiovascular disease, for example E4 is
implicated in Alzheimers disease
Apolipoprotein E (APO E) has many functions including
the transport of triglycerides to the liver and distribution of
cholesterol between cells.
It has also been shown to affect the formation of
atherosclerotic lesions by inhibiting platelet aggregation

Lipoprotein (a) ..Lp(a)

Cardiovascular disease (CVD) and more specifically,
Myocardial Infarction (MI) remains a leading cause of
morbidity and mortality, despite the targeting of LDL
cholesterol via statin therapy.
There is a need for additional causal risk factors, beyond
the
traditional LDL measurement
Large scale studies and international guidelines published,
have proven that Lp(a) is a major independent genetic risk
factor for premature CVD and should be screened in
all patients at moderate to high risk.
What is Lipoprotein(a): Lp (a)?
Lp(a) is a major independent genetic risk factor for
cardiovascular disease
Lp(a) particles are similar to LDL consisting of a
cholesterolrich core, with an apoB-100 protein
attached
Apo(a) is synthesised in the liver and binds to newly
synthesised apoB-100

Recent years have seen major scientific advances in

the understanding of Lp(a) and its causal role in
premature CVD.
Elevated Lp(a) levels associate robustly and specifically
with increased CVD risk. This association is continuous and
does not depend on high levels of LDL or non-HDL
cholesterol, or the presence of other CVD risk factors.
Lp(a) levels, like elevated LDL, is causally related to
premature development of atherosclerosis and CVD.

Atherosclerosis
Atherosclerosis refers to the buildup of fats and cholesterol
in and on your artery walls (plaques), which can restrict
blood flow.
These plaques can also burst, triggering a blood clot.
Although atherosclerosis is often considered a heart
problem, it can affect arteries anywhere in your body.
When too much LDL (bad) cholesterol circulates in the
blood atherosclerosis is initiated by inflammatory
processes in the vessel wall in response to retained lowdensity lipoprotein (LDL) molecules.
Once inside the vessel wall, LDL molecules become
susceptible to oxidation by free radicals,and become toxic
to the cells.
The damage caused by the oxidized LDL molecules
triggers a cascade of immune responses which over time
can produce an atheroma
The body's immune system responds to the damage to the
artery wall caused by oxidized LDL by sending specialized

white blood cells (macrophages and T-lymphocytes) to

absorb the oxidized-LDL forming specialized foam cells.
These white blood cells are not able to process the
oxidized-LDL, and ultimately grow then rupture, depositing
a greater amount of oxidized cholesterol into the artery
wall. This triggers more white blood cells, continuing the
cycle.
Eventually, the artery becomes inflamed.
The cholesterol plaque causes the muscle cells to enlarge
and form a hard cover over the affected area.
This hard cover is what causes a narrowing of the artery,
reduces the blood flow and increases blood pressure.
Eventually, an area of plaque can rupture (break open).
This causes a blood clot to form on the surface of the
plaque. If the clot becomes large enough, it can mostly or
completely block blood flow through a coronary artery.
If the flow of oxygen-rich blood to your heart muscle is
reduced or blocked, anginaor a heart attack may occur.
Plaque also can build up in other arteries in your body,
such as the arteries that bring oxygen-rich blood to your
brain and limbs. This can lead to problems such as stroke
and peripheral arterial disease .