Re: ApoB/ApoA1 ratio and its significance to CHD - Chris M.

[Guest guest]

It appears I'm somewhat confused. I was under the impression that ApoB is a

rough

measure of the number of LDL particles in circulation. A higher ApoB measure

would

indicate a higher number of LDL particles, which suggests that the particles are

small and

dense (pattern . However, the authors state below that the risk associated

with smaller

LDL particles is independent of apoB concentrations. Both are risk factors (in

fact, elevated

apoB concentrations + elevated small, dense LDL particles = 6x higher risk of

CHD) but

they are not necessarily related.

If ApoB is a marker of LDL particle number, how could ApoB be high without

signifying an

increase in small, dense LDL?

Chris

" In the present report, the risk associated with smaller LDL particles appeared

to be

independent of the concomitant variations in apo B concentrations and thereby of

particle

number (Tables 2 and 3). Elevated apo B levels were also associated with an

increased risk,

independent of the LDL particle size. However, the presence of small LDL

particles

combined with elevated apo B concentrations resulted in the greatest increase

(sixfold) in

the risk of IHD (Fig 3). We also found that apo B concentration was the best

metabolic

predictor of IHD risk in multivariate analyses both in the present case-control

analyses

and in the study of the whole cohort of the Quebec Cardiovascular Study.34 These

results

support the hypothesis put forward by Tornvall et al11 that LDL particle number,

in

addition to LDL composition, may be important with respect to IHD. "

[Guest guest]

Look at me - I'm having a conversation with myself!

I was mistaken about the meaning of the ApoB/ApoA1 ratio. ApoB is a rough

marker for the

number of LDL, IDL and VLDL particles in circulation, and ApoA1 is a marker for

HDL. So this

is measuring the ratio between LDL-IDL-VLDL and HDL.

Still, I wonder about the correlation between a high ApoB/ApoA1 ratio and small,

dense LDL.

I also wonder whether a high ApoB/ApoA1 ratio is actually a causative factor for

CHD, or if it

is simply an association - as could be argued in the case of high LDL levels.

What do you think, Chris?

[Guest guest]

Thanks for your reply, Chris.

I guess the question behind my musing on whether a high apoB/apoA1 ratio is a

cause of

CHD or simply correlated with it stems from my ongoing investigation of whether

LDL is

actually a risk factor for most people.

There's a lot of contradictory data out there. Ravnskov et al. have presented

some pretty

convincing evidence that LDL isn't a risk factor when it comes to CHD mortality

or total

mortality. And there's a lot of data which shows that high cholesterol in the

elderly is

protective, whereas low cholesterol increases chances of dying from a heart

attack.

I think the Interheart study mostly looked at incidence of AMIs, and not at

total mortality (I

have to check this, though).

They found that a high apoB/apoA1 ratio was the single highest predictor of AMIs

-

increasing the risk by 3.25x. Second was smoking, and third was stress. It was

a huge

study with 30,000 participants in 52 countries.

I guess it's difficult to say for sure whether the high LDL/low HDL was

causative or simply

a marker for an underlying inflammatory condition, stress, etc.

Chris

[Guest guest]

> I haven't evaluated all the information out there, but usually when

> the study is negative, as far as I've seen, there is a positive

> association that doesn't reach statistical significance. This is

> especially true in the older groups, where you go from a pretty strong

> and significant association in young people, to a weaker and

> non-significant association in older people, and then no association

> for people in their 70s and an inverse association for people in their

> 80s. I think there are a lot of folks who tend to treat

> non-significant findings as the same thing as negative findings, when

> in actuality it could just mean the study didn't have the statistical

> power to pick up the association.

But again, is this an association or a cause? As you pointed out in your Rho

activation

article, with inflammation we might expect to see higher LDL because of

increased

synthesis of mevalonate but inhibition of squalene synthase. Likewise,

cholesterol is the

precursor to all stress hormones so perhaps the elevated levels of LDL are

simply a marker

for stress - and it is actually stress that is causing the heart disease, not

LDL.

Maybe that's why we see a decreasing correlation between LDL and CHD as people

get

older. Young men tend to have much more stress in their lives, so we'd expect

to see

higher levels of LDL in those populations. As men & women get older and retire

from the

workforce, it's likely that their stress levels decline. Of course their LDL is

still elevated,

but perhaps for reasons other than stress - reasons that are less atherogenic

and

causative for CHD.

> Comparatively far fewer studies have looked at ox-LDL, and this

> association is much stronger. The proportion of oxidized

> phospholipids in the LDL particle multiplied by the total LDL level

> (and thus the total concentration of ox-LDL) is eight times more

> predictive than the LDL level itself.

Yes, I'm pretty convinced of this now. If you happen to remember where the 8x

statistic

came from I'd love to see that reference.

> > And there's a lot of data which shows that high cholesterol in

> > the elderly is

> > protective, whereas low cholesterol increases chances of dying from a heart

> > attack.

>

> Right, though this is in the very old -- like in the 80s.

Yes, but still significant in my mind. Why would something that is supposedly a

risk factor

in younger people suddenly stop being a risk factor in older people? No one has

explained this adequately to me yet. It's like saying that smoking causes lung

cancer in

young people but not in old people.

Chris