1/ The Hospital Analogy
It's unsurprising to find hospitals are associated with greater illness and death.
This is intuitive because we already know people specifically go to hospitals when there's a problem they are well suited to fixing.
It's unsurprising to find hospitals are associated with greater illness and death.
This is intuitive because we already know people specifically go to hospitals when there's a problem they are well suited to fixing.
2/ But it *is* surprising for most people to find that LDL particles are associated with the immune response... but it shouldn't be.
(For those following my colleague, @siobhan_huggins, they are already well aware).
(For those following my colleague, @siobhan_huggins, they are already well aware).
3/ LDL particle production increases from cytokine signaling, damaged endothelial cells upregulate transcription and expression of LDL receptors, as does growth factor from thrombocytes (platelets).
4/ In other words, LDL dispatch and recruitment is part of the first response. And we can observe this activity w/ endothelial dysfunction and damage.
It still amazes me that this critical clue receives so little attention in modern medicine on the subject of atherosclerosis.
It still amazes me that this critical clue receives so little attention in modern medicine on the subject of atherosclerosis.
5/ Imagine you were an alien race looking at earth from a distance and you saw these blocky white vehicles snatching up the inhabitants seemingly at random to what seemed like a death trap (the hospital) given how frequently they expired there relative to everywhere else.
6/ If you didn't already know that there was literally a 911 call from the inhabitants to the hospital, it would be understandable why you'd have that misimpression.
But we know all about damaged cells calling for help with cytokines. We know LDLr is specific to LDL particles.
But we know all about damaged cells calling for help with cytokines. We know LDLr is specific to LDL particles.
7/ If you looked *only* at "hospital-related deaths", it makes perfect sense as to why one would avoid ever being in one. And to be sure, med professionals also make legitimate mistakes, but that's the problem with looking at things in a vacuum...
8/ Most of us figured hospital error was already a part of the cost/benefit equation.
We assume there's a greater likelihood of health benefit than the potential of mistakes making things worse.
We assume there's a greater likelihood of health benefit than the potential of mistakes making things worse.
9/ However, mistakes happen. These professionals are human too.
But let's take the analogy further...
How much does the environment these medical professionals work in matter to their chances of making a mistake? (I'm sure @ZDoggMD would have an opinion on that)
But let's take the analogy further...
How much does the environment these medical professionals work in matter to their chances of making a mistake? (I'm sure @ZDoggMD would have an opinion on that)
10/ Imagine a catastrophe hit nearby your favorite hospital.
More patients were coming in than they had staffed for, supplies are being taxed, computer systems are slowing due to overextended bandwidth.
Would you be surprised if the error rate climbed?
More patients were coming in than they had staffed for, supplies are being taxed, computer systems are slowing due to overextended bandwidth.
Would you be surprised if the error rate climbed?
11/ Pretend the error rate of this hospital under good conditions were around 1%. Would it surprise you if it jumped to 5% under these dire conditions?
No, of course not. Even if that's a 400% increase, you might actually consider that impressive given the circumstances.
No, of course not. Even if that's a 400% increase, you might actually consider that impressive given the circumstances.
12/ Now let's head back to LDL and atherosclerosis.
I've been asking this question to myself and all the experts since I began. In fact, I have it as a slide from several of my talks this year...
I've been asking this question to myself and all the experts since I began. In fact, I have it as a slide from several of my talks this year...
13/ Now let me ask the more provocative question directly: How much is atherosclerosis by design vs by mistake?
And spoiler alert -- I don't pretend to know the answer on that yet.
But I can say that I don't think we know enough to rule out design, and ACM is the key...
And spoiler alert -- I don't pretend to know the answer on that yet.
But I can say that I don't think we know enough to rule out design, and ACM is the key...
14/ If you had a loved one who didn't want to go to the hospital because they had a friend who died due to hospital error, you would want overall data to provide them.
"Look, this way of dying is more the exception than the rule. The odds are better for you to go."
"Look, this way of dying is more the exception than the rule. The odds are better for you to go."
15/ Likewise, I want to not only see how high LDL levels relate to all cause mortality -- I want to see how they relate when in a good environment. (AKA good health!)
In other words...
In other words...
16/ People who visit hospitals more often my have a slightly higher chance of experiencing a hospital-related error. But that's not necessarily due to hospital, that's more likely due to the greater degree of visits and need at a further challenge of care.
17/ By the same token, why wouldn't we assume an immune response that is highly taxed systemically wouldn't continually risk greater and greater chance of error?
Isn't this what we already see commonly with tobacco, alcohol, and other substances that strain the human OS?
Isn't this what we already see commonly with tobacco, alcohol, and other substances that strain the human OS?
18/ To date, I have yet to have a minimally modified study or dataset show high LDL (particularly when HDL is high and TG low) demonstrating worse all cause mortality. In fact, it usually shows the lowest LDL as the worst for outcome with age parity.
19/ And yes, this includes those with the ⬆️LDL+⬆️HDL+⬇️TG triad. In the NHANES group, of those dying by heart disease, they were almost all entirely in their 80s
20/ And of course, there's the NHANES centenarians themselves...
21/ Once again, this is observational, and such epidemiological evidence isn't good for proving causation.
But epi studies are good for knocking down claims of causation. A lack of correlation or -- even better -- the *reverse* of expectations are extremely relevant.
But epi studies are good for knocking down claims of causation. A lack of correlation or -- even better -- the *reverse* of expectations are extremely relevant.
22/ Quick aside -- many insist the lower LDL=greater ACM is actually "reverse causality", but I haven't seen this yet in the NHANES data. In fact, I ran it all they way out to 10 years.
23/ All this is not to say I'm confident the lipid hypothesis is false. But at the barest of minimums, I think there needs to be more specific examination on healthy populations with high LDL, particularly when powered by fat
Let's see what the data says.
CitizenScienceFoundation.org
Let's see what the data says.
CitizenScienceFoundation.org
