Cholesterol (the HDL sort) kills?

This article was picked up by GinnyL, a prolific reader of diabetes news and a poster on Dr Bernstein's site. There are no links to anywhere from the article, so I pubmeded the guy who got a mention by name, Dr Genest, for 2008, and came up with this ref, which I can get at the full text of.

BTW there are some interesting papers of FH he's published, maybe another day.

There's a lot of waffle but you do get the fact he is talking about EPIC-Norfolk and IDEAL. This appears to be a reasonable summary of their findings:

The more HDL particles you have the better, the less cholesterol in the particles the better. ie you want to have a high HDL-C particle count with not too much cholesterol in each particle.

Your lab work merely picks out any HDL it can find, measures the total cholesterol in this fraction and gives you that number. Compare this to the accepted wisdom re LDL-C, typically from Dr Davis:

Your lab work just picks out the LDL, measures the cholesterol and guesses (sorry, calculates) an approximate number. Actually that's completely wrong. The lab measures the TC, subtracts a few numbers, adds VAT, subtracts the first number you thought of and that's the best guess of your LDL-C concentration. Maybe.


Anyway, if your really do measure particle sizes/numbers, the fewer LDL particles you have better, the more cholesterol in each particle the better.

Are you seeing a pattern here? It all comes down to particle numbers, sizes, contents. What controls all of these? Not statin deficiencies, as in IDEAL.

Forget your cholesterol. What marker predicts heart attacks and total mortality without all of the paradoxes?

Follow EPIC and HbA1c (yes, same that same EPIC study as this one) to get some sort of clue. Control what you are doing wrong diet/lifestyle-wise to glycosylate your haemoglobin and your liver will sort out whatever cholesterol particles sizes/numbers it needs for health.

The EPIC/IDEAL paper is quite amusing for the shock horror throughout the discussion that high HDL could be killing people via heart attacks, but you get used this sort of rhetoric from cardiologists. It sort of gets summed up by Dr Genest's comments about torcetrapib:

"The second such compound, torcetrapib, proved toxic despite causing a large increase in HDL-C levels and was withdrawn from clinical use"

No, Dr Genest, think again. Perhaps it's not "despite", perhaps it's "because". Perhaps it is the artificial packing of cholesterol in to HDL particles which was toxic, not the drug per se. Treating a lab number is all torcetrapib did, it's for idiots. Sort out your diet so as to live within the limits of your own personal level of insulin resistance and leave your lipids alone. On Kitava and for the fishing Bantu this can involve 70% of calories from carbohydrate producing an HDL <1.0mmol/l with excellent cardiovascular health. For an insulin resistant Norfolk diabetic it might mean 5% of calories from carbs and the rest from saturated fat giving an HDL of 2.0mmol/l.

It's not the labels on the lipids that do the damage.

Peter

PS Also from Dr Genest

"Mutations that impair the function of cholesteryl ester transfer protein (CETP) are associated with marked elevations in HDL-C levels but not necessarily with protection against coronary heart disease (8)"

Ref (8) does not quite say that the mutation (the one which torectrapib mimicked) was neutral, it said it was bad. Naughty mis-citation. He must be a cardiologist. And people are surprised at torcetrapib killing people, using heart attacks? Torcetrapib was a success, it did exactly what it should do! The Zhong et al paper was published in 1996. It was the basis for the development of torcetrapib. You can't say Pfizer didn't know what they were doing. You can't understand why they did it either.