HEALTH: Sep 05, AU Edition

A HEART-MENDING TALE
Turning the growth of blood vessels on and off could treat not just cardiac problems, but many cancers as well
The great elephant descended and left the indentation of its foot upon my chest….a Frankenstein’s monster of zipper scars and pirated body parts. Two heart attacks and two bypass operations – six grafts in all, loops of hosing jury-rigged around my jalopy of a heart. Two major crashes, but the motor still runs.”
One of the most beautiful writers I know was almost killed by that last heart attack. There is a touching, miserable aside in Heart: A Memoir about going on a farewell tour of good food. The author, my father-in-law, barely recalls it. Defending his memory, he points out that the book is ten years old. And the motor still runs.
So you see, I have a vested interest in keeping hearts running. According to the New Zealand Ministry of Health, cardiovascular disease is New Zealand’s biggest cause of death. Now, I’ll grant you, some of those people have reached an advanced age and are in the “gotta die of something” demographic. Unsurprisingly, when very old people are autopsied, examiners tend to find not just lots of things wrong, not just the heart failure that killed them. Cardiovascular disease, however, also takes a lot of lives prematurely. To die at 50 is not a tragedy in the sense that dying at 5 years old is, but it still has the sense of a life cut short about it that dying at 80, for example, does not.
You all know the risk factors, so I will not trouble to mention that being a chain-smoking, salt-shaking, cholesterol-scarfing, diabetic couch-potato booze-hound is not good for your heart. If this is you, you need to find a sympathetic family doctor and explain that you are not quite ready to change yet, but would they be a love and give you a quick once-over. Knowing your cholesterol levels and blood pressure may encourage you to change, but even if it doesn’t, at least you can get on some nice drugs to try and slow down the damage whilst you try to work up the motivation to change.

The heart is a muscle and it pumps blood, just like the Counting Crows song tells us. Let’s simplify it for a minute, and pretend that there is simply a loop of hose going in a circle from one side of the heart-pump to the other. Of course, it is a tricky hose, it narrows into increasingly tiny vessels to supply every bit of you with blood. But it will do, as a metaphor. Blood pressure is a measure of how hard heart-pump needs to work to push the blood all the way around the hose and back to the heart. Hopefully the pump can do this easily. When blood pressure is high, the pump is knocking itself out trying to push the blood around. Probably because there is some kind of gunk (cholesterol) clogging up the inside of the hose. The clog can be in your foot, your brain, anywhere. If there is so much gunk (cholesterol) built up that the blood can’t get through it will swell up and burst. If this happens in our brain, cerebral aneurysm (stroke) ensues.
(Note to guys not motivated to change: you know how if blood supply isn’t getting to your brain, it will loose function? Now replace the word “brain” with other body parts until you feel alarmed. Some causes of impotence are avoidable. Maybe a jog, perhaps?)
If all the gunk is near the heart, and the hose is narrowed, then the heart-pump doesn’t get blood. Your actual heart, not our hypothetical pump, needs oxygen, and blood carries oxygen. If blood is not getting to your heart, it is not getting oxygen. It will alert you by causing pain. In angina, the pain is an alert that the heart is suffering, but getting some oxygen and will be OK with rest or a nitro tablet. Beyond angina, the heart keeps aching. The elephant standing on the chest is a common symptom, but the chest pain may be in the arm, shoulder, back. If you have the slightest doubt about chest pain, call the ambos. They will not be angry at you for being fine. You will be angry at yourself if your heart has been dying while you sat at home with the martyr’s wait-and-see attitude. Some people, especially women and the elderly, report symptoms other than chest pain as the primary symptom, for example sudden shortness of breath, dizziness or extreme fatigue.
We assume, at this point, that you have heeded none of my advice except the bit about calling the ambulance. You are in the cardiac care unit, having had your first or second heart attack. What are your
options? You can have angioplasty, where they get into the hose going into your heart and squash, laser or chop out the offending cholesterol. They can put a nice little stent in to hold the artery open. If things have gone past that point, you can get a CABG (coronary artery bypass graft, known as “cabbage” in the trade). The trick here is to dig up a nice big artery, probably from your leg, and jury-rig a detour for the blood to get back to your heart. Obviously there will be some chest-cracking here – it is not a low-risk procedure. Ah, but that spot of dead lazy heart is still freeloading on the rest of your heart, so you must take care.
Now imagine if you could just get the heart to grow nice new hoses, or blood vessels. Angiogenesis is the word for this, and it is an exciting idea at the bleeding edge of research. If doctors can control the growth of blood vessels then they can do two things: grow new hoses where they are needed (in cases of peripheral vascular disease and coronary artery disease) and stop cancers from growing their own blood vessels. Solid cancers need blood supplies to get oxygen and nutrients to grow. No blood, cancer dies.
Human trials are currently underway in the US to develop gene therapy for treatment of heart disease. It is a complex procedure, done at the research level. It works like this: first, researchers find a useful gene and then try to get a patent on it so that they have the intellectual property rights to develop it. (Yes, a lot of people are opposed to this, but consider the alternative: A research-and-development company thinks they have a gene that might revolutionise cancer therapy. It may take many years and a lot of money to get it to market, and many promising therapies will be dropped well before the end of the race. So, what, they should apply for an arts council grant instead?) Then the researchers trick a bacteria or mammalian cells into reproducing the gene, and then they strain it out and clean it up at a very high level. Then all they have to do is prove that what they have created – complex very large proteins – is what they have the patent for. The only thing left is to make it work.
An Australian company, Amrad, has the rights to something called vascular endothelial growth factor B (VEGF-B) and is developing potential cancer therapies with it. Specialising in cancer treatment themselves, they would license the rights to the gene to develop cardiac treatments. David Crump, Amrad’s medical director, told me, “It’s an area of a lot of interest and theoretically it should work…when it hasn’t we have to find out why. Eventually we will get it to work…but then you’ve got to prove it”. Several American companies have reached the human trial stage with these types of therapies, and there are a few coming on to the market now.
For obvious reasons, researchers are only allowed to trial new medicines in people for whom readily available treatment isn’t working. Over ten years ago, only one of the angiogenesis patients in his trial showed any particularly amazing response, and it was decided that the treatment needed much more work and wasn’t brought to market then.
Overall, it was not a particularly successful venture. But, hopefully not in the too distant future, more patients will be good responders to the new medicines. Like my father-in-law, the one good patient, very much alive today.