IS HEART DISEASE ALL DUE TO BLOOD CLOTS?

[Guest guest]

The International Network of Cholesterol Skeptics

 

 

 

 

IS HEART DISEASE ALL DUE TO BLOOD CLOTS?

 

http://www.thincs.org/Malcolm.htm#clots

 

 

by Malcolm Kendrick MD Malcolm

 

If you want to understand coronary heart disease, you cannot ignore the role

of the humble blood clot.

 

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 quote a riddle that my son came home with the other day:

 

What is greater than God

More evil than the devil

The poor have it

The rich need it

If you eat it you will die

 

Once you know the answer you cannot believe that you couldn’t see it

straightaway.