In the first post (
located Here)
we talked about the myths about Cholesterol. In this post I am going
to do my best to take a very complex issue (something I guarantee about
95% or more of Doctors don't know) and explain it in an easy to
understand way. Lets take a look at how Cholesterol is transported
through the body and what causes Coronary Artery Disease (CAD). In the
final post on cholesterol we will talk about what you can do to reduce
your chances of getting CAD.
How is Cholesterol Transported?
Cholesterol (lipids) needs to get from point A to point B in our bodies.
There are two types of substances that travel through our blood
stream. Hydrophilic and Hydrophobic. Hydrophilic substances can travel
in the blood without assistance because it is not repelled by liquid
(like salt or sugar which dissolves in water). Hydrophobic substances
need a transporter in order to travel in the blood because they are
repelled by liquid (like oil which is repelled by water). Cholesterol is
hydrophobic which means to travel around the body it needs a carrier.
That carrier is a protein molecule called apoproteins. Once they are
bound with cholesterol they are called apolipoproteins (apo). There are
two main classes of apo's, apolipoprotein A-I (apoA-I) and
apolipoprotein B (apoB). Almost all apoB in our body is found in
low-density lipoprotein (LDL), while most apoA-I in our body is found on
high-density lipoprotein (HDL).
But this all deals with the surface of the lipoprotein molecule. If you
think of this molecule as a ship, this is all dealing with the surface
of the ship. But what about the cargo? Remember, these ships are
serving as cargo carriers for the cholesterol lipids (both on the
surface and inside). Something that is important is the ratio of
lipid-to-protein which determines its density. Something with high
density is heavier for a given volume than something of low density. A
cubic inch of Lead will weight much more than a cubic inch of Styrofoam.
Remember this chart from part 1 on cholesterol?
This chart shows the rough breakdown of the different cholesterol
particles. Another way to look at this breakdown is based on the
following groupings. There are five main classes:
- high density lipoprotein (HDL)
- low density lipoprotein (LDL)
- intermediate density lipoprotein (IDL)
- very low density lipoprotein (VLDL)
- chylomicron
Now look at this table:
This table shows the relative density of these five groups. Notice the
very small difference in density between the most and lease dense
lipoprotein. But, also notice the very large difference in diameter (as
much as 100 times). The below chart gives us a more visual look at all
the different lipoproteins and their composition.
Note that ApoA lipoproteins (HDL) are tiny compared to ApoB lipoproteins
(VLDL, IDL and LDL). This figure is not to scale so the difference in
size is actually much greater than shown. As you move in size from
larger to smaller, the amount of triglycerides (TG) goes down and
protein goes up (in relation to the total volume).
Cholesterol transportation goes both ways. It travels from the gut and
liver to our cells (muscles and fat cells for energy, cell repair, etc).
It also travels back to the liver, primarily from LDL. So most of the
cleaning up of cholesterol (returning it to the liver) is done by the
supposed "bad" cholesterol (LDL). The problem is, sometimes LDL can
penetrate and deliver it's cholesterol to our artery walls. This is what we don't want to have happen. It is the ApoB particle that drives the cholesterol into the artery wall and 90-95% of ApoB particles are LDL.
Coronary Heart Disease (CAD)
The basic process is the LDL particle (LDL-P) crashes into the artery
wall and delivers it's cholesterol. This stimulates
an inflammatory response and our immune system kicks in and tries to fix
this inflammation by removing the cholesterol from the artery
wall. This immune response actually creates a space for more LDL-P to be
retained. Sort of like cement holding them in. More and more LDL-P
enter the space being created by the immune response. Eventually,
through more retention of LDL-P and advanced immune response, not only
does the artery narrow, but a cap of tissue forms which is known as
plaque. Most heart attacks occur when a piece of this plaque breaks off
and blocks blood flow.
So what causes the LDL-P to attach to the artery wall? The main reason
is when there is damage or inflammation. This inflammation is primarily
due to oxidative damage or oxidation. This oxidation could be in the
artery wall (lesion), causing an immune response and thus the build up
of white blood cells and LDL particles in the cavity that is created.
There can also be oxidation of the LDL particle itself. Studies have
shown that oxidated LDL cholesterol is 8 times stronger a risk factor
for CAD than normal LDL.
There are also some important things to know about LDL particles. Small
dense LDL particles are more likely to become oxidize than large fluffy
LDL particles. Small dense LDL particles are more likely to fit into
the lesions in the artery wall (vs. large fluffy). One of the problems
though is that particle size tests are not standardized and can vary
from one test type to the next. Also, there aren't good ways to measure
oxidized LDL. This makes testing somewhat varied. Also, particle size
is a secondary factor in that it is only important if your LDL-P is
high (more on that below).
So oxidation and inflammation is the major concern with dealing with
CAD. What are the 4 primary causes of inflammation and oxidation?
- Smoking
- Poor Nutrition
- Physical Inactivity
- Stress
We will break down in our next post how we can reduce these causes of oxidation and inflammation.
A Couple Notes about Testing and Variability in Levels:
In one person, studies have shown that with no change in diet or
lifestyle, the total cholesterol can vary by about 35 points up or down
for no reason at all. HDL can vary up or down about 9 points. LDL by
30 points. The ratio of Total/HDL up or down by 0.8. Triglycerides
(TG) about 40 points. This means a couple things. You need to see
fairly large changes in your numbers to conclude that something has
changed. Second, a single test doesn't give you the whole picture. You
need several tests to see what your average level is. So you could get
tested today and have a total cholesterol of 200 and go back in
tomorrow and have a level of 235 (or 165) and that is a totally normal
variation.
Another important point is that when you are losing weight, your
cholesterol levels will be skewed until you settle at a new body weight
(cholesterol release into blood from fat cells). So testing cholesterol
right after losing significant weight will show higher levels until
your weight has settled.
Another example is when you have non-alcoholic fatty liver disease and
you change your diet to correct this, the lipids and cholesterol stuck
in the liver will be release into the bloodstream and thus raising your
TG and LDL numbers. But this is a good thing as your liver is release
them to heal and over time the levels will go back down.
Another note is that in a Japanese study (
source)
they showed that non-alcoholic fatty liver disease can be a really big
indicator of risk for Coronary Artery Disease (CAD). Non-alcoholic
fatty liver disease increased the risk of CAD by 3 to 4 times for men
and about 14 times for women. So there are some scientist that now
believe that non-alcoholic fatty liver disease may be one of biggest
indicators of future CAD risk.
How to Determine your CAD risk
What the latest science has shown is that ApoB or LDL particle (LDL-P)
is the best indicators of metabolic syndrome (and thus CAD risk). So
what is important is the number of LDL particles not the amount of
cholesterol contained in them (LDL-C). (
source)
It is sort of a probability game. The more LDL particles there are, the
higher the chance they will crash into the artery wall and deliver
their cholesterol. The LDL particle number (LDL-P or ApoB) is the best
predictor of risk for CAD. Some statements have been made about the size
of the LDL particles as being an important factor in determining your
risk for CAD (small dense particles due to oxidation are bad, large
fluffy good), but the latest science (within the last couple years)
shows that this is a secondary factor. The LDL-P number is more
important and only when LDL-P is high does the size become important.
Take a look at this graph from Quebec Cardiovascular Study, published
in 1997, in Circulation.
 |
| Graph from Quebec Cardiovascular Study, published in 1997, in Circulation (Source) |
What this graph shows is that for patients with low LPL-P (below 120)
the size of the LDL particles does not matter (same risk of 1.0). But
for those with High LDL-P (above 120) the size becomes very important
(Those with larger particles only had a 2X risk versus a 6.2X risk for
those with the smaller particles).
There are several methods for measuring cholesterol, but I will not go into detail about the all of them (
THIS source does
it much better than I would). However, let's look at the one test that
is the most important. The best measurement and only one that actually
directly counts the LDL-P is nuclear magnetic resonance spectroscopy or
NMR for short (called NMR LipoProfile). Here is what an NMR report
looks like.
This test counts the total LDL particles (LDL-P), HDL particles (HDL-P),
apoB and apoA-I. It also measures the size of each particle. The
particle size is very telling when it comes to predicting insulin
resistance (and Metabolic Syndrome). In the results below you can see
that this person has small VLDL particles and small HDL particles. When
there are large VLDL-P, large VLDL size, increased small LDL-P, small
LDL size, reduced large HDL-P, small HDL size are markers for insulin
resistance. These findings can precede more conventional signs for
insulin resistance in many cases by several years.
What is important to note here is that the traditional LDL cholesterol
(LDL-C) of traditional tests given by most doctors today isn't the same
as LDL particles (LDL-P) and doesn't necessarily correlate to LDL-P.
In other words if your LDL-C is low, your LDL-P could still be high
(more particles which are smaller and contain less cholesterol). This
is particularly true for those with metabolic syndrome and diabetes.
(below is from
HERE with my own text to help easier understanding of this complex issue)
Patients with LDL-C between 100 and 118 mg/dL are shown without
metabolic syndrome (top) and with metabolic syndrome (bottom). In the
patients without metabolic syndrome, LDL-C under-predicts cardiac risk 22% of the time. However, when you look at the patients with metabolic syndrome, you can see that 63% of the time their risk of cardiac disease is under-predicted.
The above data was collected from nearly 2,000 patients with diabetes
who presented with “perfect” standard cholesterol numbers: LDL-C less
than 70 mg/dL; HDL-C greater than 40 mg/dL; TG less than 150 mg/dL. But
only 22% of the time did the LDL-P (the real indicator of risk) equal
the LDL-C levels. Remember that LDL-C less than 70 mg/dL is considered VERY low risk (5th percentile). But with LDL-P the real risk for 35% of these patients was above 1000 nmol/L (above 20%) and 7% were HIGH RISK.
When you do this analysis with less stringent LDL-C criteria (LDL-C
less than 100 mg/dL) the number of patients in the high risk group is
even higher. This shows that for many people with metabolic syndrome or
diabetes, the LDL-C numbers inaccurately report their real risk for
CAD.
