Radiation and coronary disease

Patrick Blanchard MD said:

tinyurl.comz9w4Open ↗

Radiation appears to induce coronary artery disease. Why then have radioactive stents and external
beam radiation (brachytherapy) become popular?

Brachytherapy has been shown to inhibit recurrent in-stent restenosis, Patrick.

Humbly,

Andrew

--
Dr. Andrew B. Chung, MD/PhD
Board-Certified Cardiologist
heartmdphd.comheartmdphd.comOpen ↗

MD/PhD said:

Patrick Blanchard MD said:

tinyurl.comz9w4Open ↗

Radiation appears to induce coronary artery disease. Why then have radioactive stents and
external beam radiation (brachytherapy) become popular?

Brachytherapy has been shown to inhibit recurrent in-stent restenosis, Patrick.

Humbly,

Andrew

--
Dr. Andrew B. Chung, MD/PhD Board-Certified Cardiologist heartmdphd.comheartmdphd.comOpen ↗

Yes, but I understand the long term patency studies show otherwise. Long term patency rates are not
as promising as the short term (less than 1 year). Why is this? What is it about radiation that is
beneficial and what about it is harmful?

--
~~~ Patrick Blanchard, M.D., A.B.F.P. Board Certified in Family Practice
familydoctor.orgblanchardOpen ↗ ~~~ SonoScore Winning against heart attack and stroke
sonoscore.comsonoscore.comOpen ↗

Patrick Blanchard said:

MD/PhD said:

Patrick Blanchard MD said:

tinyurl.comz9w4Open ↗

Radiation appears to induce coronary artery disease. Why then have radioactive stents and
external beam radiation (brachytherapy) become popular?

Brachytherapy has been shown to inhibit recurrent in-stent restenosis, Patrick.

Humbly,

Andrew

--
Dr. Andrew B. Chung, MD/PhD Board-Certified Cardiologist heartmdphd.comheartmdphd.comOpen ↗

Yes, but I understand the long term patency studies show otherwise. Long term patency rates are
not as promising as the short term (less than 1 year). Why is this?

Long term speaks to a process (progression of atherosclerosis) that is different from restenosis
(neointimal hyperplasia).

Quoted message said:

What is it about radiation that is beneficial

Halts neointimal hyperplasia (the over-proliferation of smooth muscle cells in response to injury).

Quoted message said:

and what about it is harmful?

Damages endothelial cells increasing local rates of atherosclerosis.

Humbly,

Andrew

--
Dr. Andrew B. Chung, MD/PhD
Board-Certified Cardiologist
heartmdphd.comheartmdphd.comOpen ↗

Dr. Andrew B. Chung said:

Halts neointimal hyperplasia (the over-proliferation of smooth muscle cells in response to
injury).

Quoted message said:

and what about it is harmful?

Damages endothelial cells increasing local rates of atherosclerosis.

Would you suppose that paclitaxel or sirolimus coated stents would be a superior therapy, short and
long term, to anti-restenosis radiation then?

MD/PhD said:

Patrick Blanchard said:

MD/PhD said:

Patrick Blanchard MD wrote:

> tinyurl.comz9w4Open ↗
>
> Radiation appears to induce coronary artery disease. Why then have radioactive stents and
> external beam radiation (brachytherapy)

become

Quoted message said:

> popular?

Brachytherapy has been shown to inhibit recurrent in-stent restenosis, Patrick.

Humbly,

Andrew

--
Dr. Andrew B. Chung, MD/PhD Board-Certified Cardiologist heartmdphd.comheartmdphd.comOpen ↗

Yes, but I understand the long term patency studies show otherwise. Long term patency rates are
not as promising as the short term (less than 1 year). Why is this?

Long term speaks to a process (progression of atherosclerosis) that is different from restenosis
(neointimal hyperplasia).

You did not address my question: Why is it that long term patency rates for radioactive stents or
external beam radiation are poor?

Certainly the data indicate radiation causes upregulation of atherosclerosis by stimulating
neointimal hyperplasia. In fact, injury (of any kind) to the intima will cause a neointimal
hyperplasia. Neointimal hyperplasia is considered to the be initial step of atherosclerosis induced
by injury, is it not?

Quoted message said:

Quoted message said:

What is it about radiation that is beneficial

Halts neointimal hyperplasia (the over-proliferation of smooth muscle cells in response to
injury).

The radiation injures the intima, but yet it appears to initially halt the injury response. If you
irradiate any tissue enough, it would probably halt any growth. Howver, it appears that the intima
eventually recovers, leading to an injury response, resulting in upregulation of atherosclerosis in
the coronary artery and eventual acceleration of the very process the radiation is supposed to be
retarding. Don't you find this approach flawed? If you reason out the mechanism, it appears to go
against "primum non nocere" first do no harm. I think this is an example of "hurry up and do
something, anything".

Quoted message said:

Quoted message said:

and what about it is harmful?

Damages endothelial cells increasing local rates of atherosclerosis.

The irony is that this therapy accelerates the very process it is trying to abolish.

Quoted message said:

Humbly,

Andrew

--
Dr. Andrew B. Chung, MD/PhD Board-Certified Cardiologist heartmdphd.comheartmdphd.comOpen ↗

--
~~~ Patrick Blanchard, M.D., A.B.F.P. Board Certified in Family Practice
familydoctor.orgblanchardOpen ↗ ~~~ SonoScore Winning against heart attack and stroke
sonoscore.comsonoscore.comOpen ↗

"Dr Chaos" <[email hidden]> wrote in message
"]news:[email hidden]...

Quoted message said:

Dr. Andrew B. Chung said:

Halts neointimal hyperplasia (the over-proliferation of smooth muscle

cells in

Quoted message said:

Quoted message said:

response to injury).

Quoted message said:

and what about it is harmful?

Damages endothelial cells increasing local rates of atherosclerosis.

Would you suppose that paclitaxel or sirolimus coated stents would be a superior therapy, short
and long term, to anti-restenosis radiation then?

Sorry to jump in here. That's what I've been told the research studies show - except at the edges of
the stents where less of the drugs are delivered. Also the drug eluting stents are fairly new and
most restenosis happens in the relatively near term, so I don't know how long the follow up was.

Incidentally, I have a theory that you could use radiation at the edges, but the combination would
be very expensive.

Bill

Bill

Dr Chaos said:

Dr. Andrew B. Chung said:

Halts neointimal hyperplasia (the over-proliferation of smooth muscle cells in response to
injury).

Quoted message said:

and what about it is harmful?

Damages endothelial cells increasing local rates of atherosclerosis.

Would you suppose that paclitaxel or sirolimus coated stents would be a superior therapy, short
and long term, to anti-restenosis radiation then?

That is the hope.

Humbly,

Andrew

--
Dr. Andrew B. Chung, MD/PhD
Board-Certified Cardiologist
heartmdphd.comheartmdphd.comOpen ↗

Patrick Blanchard said:

MD/PhD said:

Patrick Blanchard said:

On Mon, 15 Dec 2003 13:38:06 -0500, Dr. Andrew B. Chung, MD/PhD <[email hidden]>
wrote:

> Patrick Blanchard MD wrote:
>
>> tinyurl.comz9w4Open ↗
>>
>> Radiation appears to induce coronary artery disease. Why then have radioactive stents and
>> external beam radiation (brachytherapy)
become
>> popular?
>
> Brachytherapy has been shown to inhibit recurrent in-stent restenosis, Patrick.
>
> Humbly,
>
> Andrew
>
> --
> Dr. Andrew B. Chung, MD/PhD Board-Certified Cardiologist heartmdphd.comheartmdphd.comOpen ↗
>
>
>
Yes, but I understand the long term patency studies show otherwise. Long term patency rates are
not as promising as the short term (less than 1 year). Why is this?

Long term speaks to a process (progression of atherosclerosis) that is different from restenosis
(neointimal hyperplasia).

You did not address my question: Why is it that long term patency rates for radioactive stents or
external beam radiation are poor?

Actually, I did. To put it another way, high dose radiation, while inhibiting the neointimal
hyperplasia that leads to in-stent restenosis does not appear to inhibit progressive
atherosclerosis.

Quoted message said:

Certainly the data indicate radiation causes upregulation of atherosclerosis by stimulating
neointimal hyperplasia.

Not at the high doses for brachytherapy. Far field mantle radiation is associated with increased
rates of atherosclerosis but the degree of exposure seen by the coronaries are much less than that
for brachytherapy.

Quoted message said:

In fact, injury (of any kind) to the intima will cause a neointimal hyperplasia.

Yes with the exception of high doses of radiation which impair neointimal hyperplasia.

Quoted message said:

Neointimal hyperplasia is considered to the be initial step of atherosclerosis induced by injury,
is it not?

Not really. By itself, injury, does not cause atherosclerosis.

Quoted message said:

Quoted message said:

Quoted message said:

What is it about radiation that is beneficial

Halts neointimal hyperplasia (the over-proliferation of smooth muscle cells in response to
injury).

The radiation injures the intima, but yet it appears to initially halt the injury response.

Because at high enough doses, it also injures smooth muscle cells (and precursor cells) located in
the media and adventitia, impairing their ability to either replicate or migrate into the damaged
(and stented) area.

Quoted message said:

If you irradiate any tissue enough, it would probably halt any growth.

Correct.

Quoted message said:

Howver, it appears that the intima eventually recovers,

Yes.

Quoted message said:

leading to an injury response,

A recovered intima inhibits the injury response.

Quoted message said:

resulting in upregulation of atherosclerosis in the coronary artery

Only in those areas where the dose was not sufficient to inhibit the injury response.

Quoted message said:

and eventual acceleration of the very process the radiation is supposed to be retarding.

Ditto.

Quoted message said:

Don't you find this approach flawed?

It works.

Quoted message said:

If you reason out the mechanism, it appears to go against "primum non nocere" first do no harm.

It prevents in-stent restenosis which would cause harm.

Quoted message said:

I think this is an example of "hurry up and do something, anything".

That is one way of looking at prevention.

Quoted message said:

Quoted message said:

Quoted message said:

and what about it is harmful?

Damages endothelial cells increasing local rates of atherosclerosis.

The irony is that this therapy accelerates the very process it is trying to abolish.

Only in areas where the radiation dose was inadequate.

Humbly,

Andrew
--
Dr. Andrew B. Chung, MD/PhD
Board-Certified Cardiologist
heartmdphd.comheartmdphd.comOpen ↗