Other possibilities...

david.

IS HEART DISEASE ALL DUE TO BLOOD CLOTS?
http://www.redflagsweekly.com/kendrick/2003_mar21.html
By Malcolm Kendrick MbChB, MRCGP (email - [log in to unmask] )

Up to now I have resisted writing about this area, as blood clotting is a
mind-boggling and complicated area of human physiology. In the end,
however, if you want to understand coronary heart disease (CHD), you cannot
ignore the role of the humble blood clot.

For it is now accepted by everyone involved in CHD research that the final
event, the thing that kills you with CHD, is the formation of a blood clot
on top of an atherosclerotic plaque. If the blood clot is big enough to
completely block a critical artery, in a critical area, you will die.

In the last few years medics have become increasingly expert at trying to
clear these potentially fatal clots. Aspirin is the first line of defence,
then the clot busters streptokinase, or tissue plasminogen activator (tPA)
are used.

Increasingly, cardiologists get to work with thin wires and balloons, and
stents, to remove the clot, prize the artery apart, and stick a metal
framework to keep the artery open after unblocking it. New drugs have been
developed to keep the artery patent. This is all great stuff, and many
thousands of people who used to die are now being saved.

So there is no argument from anyone about the final event in CHD. It’s a
blood clot. It is also recognised that blood clots develop over
atherosclerotic plaques on quite a regular basis without causing any
symptoms at all, presumably because they are not big enough to fully block
the artery.

However, in these silent episodes, once the blood clot stabilises it adds
to the plaque size, and can lead to greater narrowing of the artery. In
this way, repeated blood clots forming over an area of existing plaque
cause atherosclerotic plaques to ‘grow’. And if you look at plaques
closely, you can — in many plaques — clearly see bands, with each band
indicating an episode of plaque growth.

This is all agreed upon by almost everyone. And if you were a simple soul,
like me, you might argue that if plaques grow, and eventually kill you due
to clots forming on the artery wall, could this not be how they start in
the first place? Are atherosclerotic plaques not, in fact, just the
remnants of repeated blood clots, which are ‘drawn in’ to the artery wall,
in time turning into a form of scar tissue?

If you did think this, you wouldn’t be the first. This hypothesis was
initially proposed by Karl Von Rokitansky in 1852. Although supporters of
Rudolf Virchow may argue that he said it first. Unfortunately, therefore, I
can hardly claim that this idea is either new, or mine.

Can it really be that simple? Surely there must be something wrong with the
hypothesis that atherosclerotic plaques are the remnants of repeated blood
clots? Where does this idea break down? I could say, don’t ask me, I happen
to believe it’s true. But I will attempt to be a little more objective than
this.

The key point of objection is that, whilst you can see how blood clots can
form over a ‘damaged’ artery wall, it is very difficult to see how they
form over a healthy artery wall. After all, a critical function, perhaps
the critical function of the lining of the artery (the endothelium) is to
prevent blood clots from forming. So how can this process actually start? A
good point from my learned friend.

But I put it to you, members of the jury, that every ‘factor’ that has been
identified as increasing the risk of CHD, has clearly identifiable
pro-coagulant activity. Equally, every factor that has been identified as
reducing the risk of CHD has clearly identifiable anti-coagulant activity.
Which, I would vouchsafe, is pretty heavyweight proof.

Is this really true?

Well, yes. But you have to understand that there are three interconnected
factors at play here that can cause a clot to form over the artery wall.
Factor one, is ‘damage’ to the endothelium. Once damaged, the endothelium
stops acting as a non-stick anti-coagulant surface. Indeed, if the
endothelium is stripped away, it exposes the middle layer of the artery,
the media, to the blood, and the media releases the most powerful
pro-clotting factor known to man: Factor VII, the ‘extrinsic’ factor.

The second factor is how pro-coagulant the blood is itself. There are a
multitude of clotting factors in the blood. Some of which you may have
heard of, such as factor XIII - the one that is missing in haemophiliacs;
some of which you probably haven’t heard of e.g. Von Willibrand factor.
Increase a pro-coagulant factor, and you increase the chance of clots forming.

The third factor is the structure of the blood clot itself. Some clots are
wobbly and weak; others are very tough, and difficult to break up. For
example, incorporated into all blood clots is a substance called
plasminogen. This is an enzyme which, when activated, chops the clot into
pieces. (Which is why tPA — tissue plasminogen activator - is given to
people having a heart attack) However, if you have a high level of
Plasminogen activator inhibitor — 1 (PAI — 1) in the blood, plasminogen is
less effective at breaking the clot up.

So, you have to look at three basic factors:

The anti-coagulant status of the endothelium
The pro-coagulant state of the blood
The relative ‘toughness’ of the blood-clot once it is formed
Bearing this in mind, I think it is interesting to run through a few
factors known to alter the risk of CHD, and see how they fit:

Smoking:


Smoking creates free-radicals in the blood, these reduce nitric oxide (NO)
synthesis in the endothelium, and NO is the single most powerful
anti-coagulant factor in the body. Smoking also has pro-coagulant effects
in the blood; it raises fibrinogen levels. It also has endothelium damaging
effects. So, if you want to avoid CHD… STOP SMOKING!

Drinking:


Ethanol, in moderate doses, reduces free-radical synthesis, reduces
clotting factors, such as fibrinogen, and reduces the blood clot toughness.
However, excess alcohol consumption creates rebound platelet stickiness
(platelets are hugely important in blood-clotting). Moderate drinking
protects against CHD, heavy drinking is a risk factor.

Diabetes:


A high blood sugar level leads to increased free-radical synthesis, see
above. A high blood sugar, independent of its effects on NO synthesis, also
causes endothelial ‘damage.’

Haemophilia:


Not surprisingly, haemophilia reduces blood coagulability. Haemophilia also
reduces the absolute risk of CHD by 80%.

Statins:


Statins have strong anti-coagulant effects, they stabilise plaques and
increase NO synthesis.

Aspirin:


Aspirin reduces the stickiness of platelets (see alcohol). Platelet
aggregation is the first step in blood clotting.

Omega-3 fatty acids


Omega-3 fatty acids have strong anti-coagulant effects in the blood

Stress


Physical, or psychological stress causes the release of the stress
hormones: cortisol, adrenaline, growth hormone and glucagon. These hormones
all increase blood coagulabiltiy, raise the blood sugar level (see above),
and ‘damage’ the endothelium.

Raised blood pressure


I am a little ambivalent about this risk factor. I am unconvinced that a
raised blood pressure really is a ‘cause’ of plaque development. However,
it is possible to see how high pressure, and turbulent blood flow, could
strip away a layer of endothelium, exposing the blood to the media, and
thus factor VII, thus stimulating a blood clot to form. It is certainly
true that plaques don’t form in low pressure blood vessels (e.g. veins).

However, the clinical trials on blood pressure lowering are very
unconvincing when it comes to a correlation between the degree of blood
pressure lowering and the prevention of CHD.

HDL


HDL has strong anti-coagulant effects

LDL (Oxidised LDL)


This is a complex pathway. When platelets start to stick together, they
release free radicals. Free radicals oxidise LDL. Oxidised LDL is a
powerful blood clotting factor. LDL is also incorporated into the blood
clot as it forms, and provides a ‘lipid’ surface (along with VLDL) for the
construction of fibrin. Fibrin is the hugely strong protein strand that
binds a clot together and makes it ‘tough.’

Frankly, I think that’s enough. If you wish to, it is possible to link
every single factor known to have an impact on CHD rates to one of three
effects: endothelial damage, blood coagulation, or toughness of the clot.
If you don’t affect any of these three things, then you have no effect on
CHD rates. If you manage to impact all three, then it’s time to increase
the life insurance. (On a positive note you won’t need a big pension fund).

So, if it’s that simple, then why have you never heard of this before? Now
that is another story altogether. But if enough people think I am making
all of this up, then I will provide a series of references from prestigious
journals to support every single fact that I have presented.

To my mind, the answer as to the underlying cause(s) of CHD is not only
‘out there,’ it has been staring everyone in the face for the past fifty
years. Perhaps it is too obvious for anyone to see it.

To unsubscribe send one line: unsubscribe click4hp to: [log in to unmask] . To view archives or modify subscription see: http://listserv.yorku.ca/archives/click4hp.html