Thursday, January 01, 2009

Cholesterol: LDL in Oslo

There is a group of doctors in Oslo who run a coronary care unit and, as part of their day to day work, they do quite a bit of coronary arteriography. They put in the dye and look at the arteries. It's part of their job. I assume they are quite good at it.

They did something very, very strange and then wrote a letter to the editor of the JACC about it, presumably because they couldn't get it published in any other way.

This is what they did.

They simply selected sequential patients with LDL cholesterol scores below 2.7mmol/l. In the old terms that so much cardiac work is published in I think this means an LDL of below 100mg/dl. Quite why anyone with an LDL this low would need a coronary arteriogram is a good question to ask anyone who believes in the lipid hypothesis.

They ignored all people with LDL concentrations from 2.7 to 4.5mmol/l but did enroll all people with an LDL >4.5mmol/l, that is above about 180mg/dl.

So they then had two groups of people, those at catastrophic risk of LDL-blocked-arteries and those with so little LDL they couldn't stick a tail to a donkey, or absorb a bacterial toxin, with it.

They did the scheduled angiography and checked how many patients had >70% blockage of at least two coronary arteries in each group.

Guess what: LDL cholesterol doesn't matter. They recruited 47 patients with low LDL-C, of whom 21 had significant CAD. They got 46 high LDL-C patients, of whom 24 turned out to have CAD.

I know that this is a calculated LDL value, not a particle number etc etc etc but this calculated guestimate is the basis of the lipid hypothesis in its current persona, until it gets its next adhoc makeover.

To a cholesterol sceptic that's pretty much what you would expect, serious heart disease affects people pretty well independently of LDL value and no one should be surprised at this. There is nothing strange in the study so far.

The really weird thing that the Oslo group did was this, wait for it:

They went looking for what might really cause heart disease!

Where do you start looking in a wide open field like this? It's almost like having virgin soil to plough...

It turns out that it's pretty easy to differentiate the groups with heart disease from those without. Here is a list of things which are significantly different between the patient groups with heart disease and those without it, in no particular order:

Ability of arterioles to vasodilate in response to applied acetylcholine

Level of von Willebrand factor (a platelet adhesion factor)

Level of hsCRP

BTW: Remember the JUPITER fiasco? Elevated hsCRP in the Oslo study marked out the groups with at least two severely stenosed coronary arteries, irrespective of LDL level. JUPITER subjects with elevated hsCRP would fit in to the low LDL-C with severe CHD grouping in this study. That is; they quite probably had CHD. Back to Oslo:

Level of TNF alpha

There is an inverse effect of interleukin 10 (it's anti inflammatory)

Enhanced platelet activation as assessed by soluble CD40 ligand

Levels of endothelial and platelet activation as assessed by soluble P selectin

Blood flow response to sodium nitroprusside couldn't distinguish CHD groups from non CHD groups any more than LDL-C could.

Exactly what all of these things mean at the molecular level is not too important, though I'd bet a fair few of them are controlled by NFkappaB (hence by hyperglycaemia and hyperinsulinaemia). What matters to me is that (a) LDL cholesterol doesn't matter and (b) there are at least eight researchers in the cardiology community who are looking for the cause of CHD.

Thank goodness someone is. Good luck to them.



Bryan - oz4caster said...


Interesting post and I love your sense of humor:

"The really weird thing that the Oslo group did was this, wait for it: They went looking for what might really cause heart disease!"

My guess is too much dietary sugar (mainly fructose), too much dietary polyunsaturated fat (mainly omega-6), and chronic stress are the top factors in both heart disease and cancer, but certainly not the only factors. Chronic deficiency of vitamins A, D, and K2 may also be important.

L said...


I had a physical last week.
Tri 43
HDL 88
LDL 152
Total Chol 249

I'm being sent to a cardiologist tommorrow. Should I be?


Peter said...

Hi L,

I've had two glasses of wine (which is a lot for me) and I'm tempted to be very very very facaetious. I won't be. This isn't funny.



L said...

I told my GP my mum has heart disease (triple bypass at 50, high cholesterol, high blood p, 98% blockage in one artery that can't be bypassed). I was told I'm at risk (age 33, smoker). She (doctor) said "your numbers" don't look good. I've never had any chest pain or other symptons. Based on "my numbers", am I at risk?


Peter said...


Your lipid numbers look like you eat a high fat, low sucrose/fructose diet. This is excellent.

Now you just need to know what causes heart disease and get checked for that. Unfortunately your cardiologist will think it is cholesterol, especially the calculated LDL value.

BTW My calculated LDL value is higher than your TOTAL cholesterol level. I have an EBCT score of seven.

Better find out if you have heart disease. You cannot tell from lipids (though yours look excellent to me, from my idiosyncratic perspective). EBCT looks at the disease process itself, not some surrogate marker. Use it.

Nicotine is a massive gorilla sitting on your shoulder. It makes heroin look like a coffee addiction. Be prepared to fight and win in a major battle with it. Possibly your life depends on it. I told you I'd had some wine!

Seriously, get an EBCT scan (I guess you are in the USA) and listen to Dr Davis and Dr G B. If you have a significant score they are in the game of reversing it. Even if Dr D believes totally in the lipid hypothesis, he does good stuff in the name of lipid manipulation.

Good luck with the gorilla.


L said...


Thanks for the quick response. Will keep in mind when I visit cardiologist tommorrow.

That's a neat trick guessing my diet. No fruit or sugar. Neglible veg.

Dr. B G said...

Peter -- Great post!!

L --

You diet is great and you will escape the fate of your family with it! Good job!

Smokers can still escape (I have my own fingers 'crossed' b/c I quit last summer).

You mother could've had (one or all):
--elevated homocysteine
--elevated high blood pressure
--elevated Lipoprotein (a) (pronounced 'little a')
--hypercoaguable states (protein C deficience, factor V Leiden, etc -- any history of DVTs/leg clots? miscarriages?)

(and Smoking worsens all the above)

Women are killed by heart disease about 6x more frequently than's for some reason a little known fact. It's a bigger killer than breast cancer.

Good luck w/the gorilla!! And the EBCT scan (even if you do have a signficant score, remember it's all reversible/stabilizable!)