Saturday, November 18, 2006

Cholesterol Bogeyman

I was going to suggest it is currently accepted wisdom that an elevated blood cholesterol level is a "risk factor" for heart disease. That is not strictly true as there is a small group of medical practitioners who object to the idea that elevated cholesterol is a cause of heart disease. This even applies to those doctors who are so enthusiastic about cholesterol lowering drugs (statins) that they preach that everyone should take a statin IRRESPECTIVE of their cholesterol level. I find it hard to find a more convincing argument that cholesterol is irrelevant.

Anyway, let's look at one of the few reasonable cholesterol lowering trials ever completed. It was done in Japan. It simply involved taking 47,294 men, all of whom had a total cholesterol level above 240mg/dl (that's 6.15mmol/l in new money, but the paper is written in Noddy units). Everyone got either 5mg or 10mg of simvastatin per day (I presume based on body weight, the authors forgot to say how they decided!). They followed them for six years, then looked at death rates.

Now one strange thing about humans is that we are all different. If you give a big group of people the same dose of a drug most people will respond to it. Some by a lot, some by a little, a few not at all. That's exactly what happened. So now we can split those 47,294 men up in to those who lived with high, low or medium cholesterol levels for six years, all of whom had the same dose of simvastatin kicking around in their blood stream.

What do you get? I like death rates as a measure of outcome. There is no arguing with an outcome of being dead or a live. It's pretty clear cut. Even to a cardiologist. So what happened to death rates?

Those men who's cholesterol level ended up between 200 and 219mg/dl had the lowest risk of dying. In fact if the value ended up anywhere between 180mg/dl and 259mg/dl the risk of dying was pretty much the same as in the lowest risk group. Anything above 260mg/dl was associated with increased mortality. Above 280mg/dl the effect was most marked. Mostly heart disease. I'll write about inherited familial hypercholesterolaemia another day.

Wow, cholesterol must be really bad for you! Except there were a number of men who developed cholesterol levels below 160mg/dl on this dose of drug. Now this is a cholesterol level which would might once have made a cardiologist very happy. I believe they are harder to satisfy nowadays. How good for your overall health is a cholesterol level below 160mg/dl? Well, in this study, by six years later you are considerably more likely to be dead than if your level had only dropped to 210mg/dl. In fact you are 2.76 times more likely to be dead. This is actually a marginally higher death rate than if you had failed to respond to the drug at all. But your cardiologist would still be happy because the excess death rate is not due to heart disease.

The men who dropped their cholesterol below 160mg/dl tended to died of cancer.

Imagine going to your doctor and being offered a pill which would switch your future life from one ending in heart disease to one ending in cancer. Well, we've all got to die some time. Which disease would you prefer? Go on, really. A quickie heart attack or the big C?

By the way the Japanese appear somewhat more clued up about heart disease that the West. A nice commentary here. Pity the free full text is in Japanese!

Saturday, November 04, 2006

Sweet Heart Disease

Sugar is sticky. Not just on your fingers, it's sticky in your bloodstream too. The higher your blood glucose concentration rises, the more glucose sticks to the haemoglobin in your red blood cells. It's easy to measure how much this has happened and it gives a pretty good idea of how sugary your bloodstream has been over the last few months. It's called the HbA1c value. Wouldn't it be fun to get together a few thousand people and measure how sugary their blood is, then wait and see how many die in the next six years? Well, even if you don't think so, the EPIC researchers thought it might be, so they did just that.

If you filled a room with 100 people, all with a HbA1c below 5% in 1997, and then invited the same 100 people back for a chat in 2003, how many empty places would there be at the second meeting? The answer is that about 4 people would be absent through having died. If you had a separate meeting arranged for people who's HbA1c was over 7%, how many empty seats might there be after that same six years? The answer is about 19. Having high sugar in your blood is very bad news. Those are the figures for men, the approximate numbers for women are 2 deaths in the low HbA1c group and 25 deathsin the high group. It's a simple relationship, the higher the HbA1c, the worse the outcome.

What did these people die of, associated with their high sugar levels?

Heart disease appeared to be quite important.

Did the researchers check cholesterol levels? You bet they did! Nil, zero, zilch association with heart disease.

So I'll stick with my six eggs for breakfast and pass on the toast and marmalade.

Thursday, November 02, 2006

Food Pyramids, food and pyramids

The people who built the Egyptian pyramids developed arthritis. That's what you might expect from pushing around 20 tonne blocks of stone with a few levers. There is an very interesting article on the excavation of the graves of pyramid builders in National Geographic. They are not talking about the pharaoh and the like, but about the people doing the donkey work.

To an archeologist this arthritis does not come as a surprise. Hard labour should produce lots of wear and tear. What is a little more strange is the fact that the Egyptian women were also severely affected. There are no depictions of women moving stone blocks. What is even stranger is that much of the arthritis is found in the women's necks. How heavy a water jug do you have to put on your head, and for how long, to develop severe degenerative arthritis of your cervical spine?

The answer is you don't have to do it at all. Spinal arthritis is rife in the modern, sedentary, middle classes of London or any other city. How many people do you know who are free of back problems? You do not need to be moving pyramid blocks to develop ankylosing spondylitis. But you do need to eat grain.

There is a fairly innocent little bug called klebsiella pneumoniae which lives not only in the soil but in the intestine of many of us, probably most of us. It is a niche bacterium which exploits a particular food source. It eats starch, but not just any starch. Starch is made of long chains of glucose. The chains are branched. At the branch points there are triplets of glucose which will not fit in to the normal digestive machinery possessed by human beings, so they get left undigested. Klebsiella eats these triplets of glucose. It has a special enzyme, pullulanase, to break them down. Happy bacterium.

Unfortumately there is a large subgroup of the population who's immune system "sees" pullulanase as something to attack. These people have a special marker on their white blood cells called HLA B27. They attack pullulanase as if it were an invading nasty. It is unfortunate that the structure of pullulanase and the structure of the collagen which forms our joints is similar. An attack on pullulanase results in collateral damage to the collagen of our ligaments and joints, most particularly those of our spine.

You don't need to carry 20 tonne "lego bricks" around on your head to get cervical spinal arthritis. You just have to eat grains and be unlucky with your HLA type. The Egyptians were amongst the first people on Earth to eat spelt, a precursor of wheat, and they suffered. So here's the £20,000 question; is the USDA Food Pyramid currently causing more arthritis than did the building of the Egyptian Pyramids?

How's your backache and would you like another slice of bread?