[hankbond]

What is the current state of understanding on high cholesterol as a leading or trailing indicator of poor health? I vaguely remember reading one theory that cholesterol was used by the body to mitigate arterial damage from other causes?

[cthalupa]

It (Particularly ApoB/Combining LDL-C and Lp(a) is one of the single largest leading indicators of health risk we have.

If anything, the data we have is suggesting we've gotten wrong what the upper limits should be for what is considered OK.

https://www.lipidjournal.com/article/S1933-2874(25)00317-4/f...

[guerby]

Isn't diabete and metabolic syndrome way more predictive than ldl or apob?

Do you have a reference comparing the various factors?

[eternauta3k]

Peter Attia had a great series of blog posts on this before his fall from grace:

https://peterattiamd.com/the-straight-dope-on-cholesterol-pa...

He also had a series of podcast interviews about this with Tom Dayspring.

I believe his explanations are all mainstream, except he favors treating LDL and LP(a) more aggressively than normal doctors

[leopoldj]

Wow the guy did Mechanical Engineering and Applied Math before going into medicine and surgery.

[stavros]

Wait, why did he fall from grace?

[messel]

I didn't know either, not sure of veracity but https://share.gemini.google/0YDt55yyfITs

[eternauta3k]

Epstein files showed he neglected to visit his seriously sick son because he was hanging out with Epstein. He still knows his stuff, asshole or not.

[hammock]

1700 mentions of his name in the Epstein files that Trump released.

[shlant]

the literature is very clear about the relationship between high LDL and Atherosclerosis. Are you referring to poor health in general, separate from Cardiovascular Disease?

[sn9]

There isn't a conflict between cholesterol having a useful role in the body and too much being harmful.

There are mountains of evidence establishing a causal relationship between elevated cholesterol levels and heart disease.

[Eddy_Viscosity2]

We've been testing for cholesterol for a long time now and have had other meds to lower it. It should be possible to see if lowering cholesterol via medication results in improved life expectancy or reducing cardiac events. I would think this study has been done a few times already. As someone who does not have much medical knowledge, I'm not even sure how to look this up or be able to assess what I see if I did.

[cthalupa]

Just google 'mortality data statins' and there's a mountain of it.

5 years studies show minimal or no benefit for people in low-risk groups. High-risk groups see significant benefit Follow up/longer term studies show increased benefit in low-risk groups but obviously not matching the high risk groups.

[BiteCode_dev]

All the answers are smart sounding and completely avoid to address your main point. Same with most doctors I asked it to.

[barnacs]

It turns out LDL has different subfractions based on size. Normally, the liver produces large ones which shuttle fat around the bloodstream, lose their payload and shrink then the liver reabsorbs them and the cycle continues.

The problem appears to begin when these LDL molecules hang around for too long. They are damaged by external factors in the bloodstream (eg. glycation due to high blood glucose, oxidation due to fragile polyunsaturated fats) and not recognized anymore for recycling. That's when they can start forming macrophages.

tl;dr LDL by itself is an incorrect measure of cardiovascular risk. Big pharma still profits by selling everyone LDL reducing drugs.

one authentic source: https://www.youtube.com/watch?v=fVLZA0qp-wc

[grep_name]

I have heard this too, and that cholesterol measurements are flawed because they don't account for particle size. That you can actually have better 'numbers' but worse results, if you reduce particulate size but also overall volume. It's frustrating that the science behind cholesterol is constantly in wild flux, but at any discrete moment you're expected to accept whatever the momentary consensus is.

Interestingly, my dentist, who also has a bit of a fixation on cholesterol on a personal level and is educated on the matter, has said that a heart calcium scan is the best way to determine what someone's target cholesterol number should actually be, and that it should not be the same from person to person.

This was after I voiced my frustration to him at having made lifestyle changes to get my cholesterol down in order to avoid getting put on statins (not wanting yet another daily drug if I can avoid it), getting the my number below the target of 110, only to shortly after that find out that they'd lowered it to 70. I talked to my endocrinologist about it, and she basically said "yeah, those numbers are more-or-less unachievable. But we want to be extra careful for type 1 diabetics, so we hold them to a higher standard. Either way, everyone gets put on statins at some point anyway, so who cares?"

I'm absolutely allergic to "everyone goes on x medication, so stop whining and go on x medication" as a medical argument, and will probably just deal with being labelled non-compliant over this one unless my cholesterol reaches a level I actually personally find to be too high at this point. Which sucks to have to do, but hey, it's my body after all, and so far doctors have failed to make a convincing case for me personally here.

[cthalupa]

VLDL is worse than regular LDL but high LDL in general is an issue. The science here isn't "If your LDL is denser everything is just peachy and you can be fine with 100 LDL," it's "You might be anywhere between significantly worse and marginally better than your numbers suggest"

If your LDL is in the 80s, you are almost certainly progressing plaque buildup regardless of all other factors. It won't be particularly fast in most people, maybe not even enough to matter over your lifespan unless you have other risk factors. If everything is favorable, you might see a halt or slow regression in the 70s, but this is like perfect storm levels of factors.

Most people need to be below 60 to start see soft plaque begin to retreat, with under 55 being the general target for high-risk individuals that need regression.

Your endo is right that basically no one gets there without some form of medication. It sucks, but it's also reality.

> my dentist, who also has a bit of a fixation on cholesterol on a personal level and is educated on the matter, has said that a heart calcium scan is the best way to determine what someone's target cholesterol number should actually be, and that it should not be the same from person to person.

Your dentist is an idiot and very much obviously not educated on the matter and should stick to teeth. CAC is a huge trailing indicator because it shows only calcified plaque. Plaque exists and blocks arteries long before it is calcified. 5+ years. People regularly have massive arterial soft plaque buildup with minimal or 0 calcium scores. And soft plaque is almost always the part that ruptures and breaks away and you throw a clot resulting in a heart attack or stroke.

A CCTA will let you see soft plaque which could potentially help give you a better understanding of just how aggressive you need to be... But the problem there is that the target for everyone should still be keeping their LDL as lower than we have been targeting for years. And if they have other atherogenic particle load, like high Lp(a), then that numbers needs to be commensurately lower to account for the combined load.

I'm not telling you to go on statins. I'm not your doctor. I'm not a doctor at all. But I do have risk factors that require I pay careful attention to this sort of thing, and I spend a lot of time reading research here because I like being alive and want to stay alive in a generally healthy state for as long as I can. And if you are the same, then, well, I would suggest listening to your doctors. They're telling you to get your LDL to that level because they think it will improve your health outcomes, and the vast, huge, overwhelming majority of research over the past decades points towards lowering LDL as being hugely important for improving ASCVD outcomes in at-risk populations across a wide variety of study types, including MR genetic studies looking at health outcomes in people that effectively do not produce LDL in their liver (in fact these studies are what really inspired the class of medicine in the article to begin with) and they basically just don't die of ASCVD. You have other options besides statins, too. Ezetimibe. These new inhibitors - hopefully the small molecule version will be more accessible than the MAB version.

[Scoundreller]

You might be missing out on any benefits from statins that are independent of the cholesterol reduction. It’s non-zero and debatably substantial.

[amanaplanacanal]

What are the other benefits?

[cthalupa]

Significant inflammation reduction, which is another factor in ASCVD. More plaque sticks to you the more inflammation there is. It's a feedback loop, as well. There are some that will even claim inflammation is the real villain in ASCVD, not atherogenic particles. That's not the majority position and ignores a metric ton of research, but what both camps are in agreement on is that more inflammation makes the situation worse.

Another is that they help stabilize plaque - by calcifying it. Which sounds like a bad thing, until you realize some of the greatest risks here come from plaque breaking off, which soft plaque is way more likely to do. Calcified plaque restricts bloodflow, but doesn't throw bits of it off to cause even bigger issues.

[dev_l1x_be]

You should check which part of your body has the most cholesterol.

[shermantanktop]

How would I check the parts of my body for that?

[dev_l1x_be]

The brain is the most cholesterol-rich organ in the body. While accounting for only 2% of body weight, it contains roughly 20% of the body's cholesterol. It is essential for nerve cell communication, learning, and memory.

[amanaplanacanal]

I think they meant ask Google. It's the brain.

[_kidlike]

cholesterol is one of the most crucial molecules for survival. It's used to create and maintain cell membranes, and other critical functions. The vast majority is created by the liver, and there are a lot of regulating signals for how much, which is where usually things go off. Low cholesterol production is an extremely serious condition. The "only" problem with high cholesterol is that it builds up inside artery walls, which eventually may or may not dislodge and may or may not cause a heart attack or an embolic stroke. (I'm not a doctor. I just get medication for high cholesterol and have done some research)

[cthalupa]

> Low cholesterol production is an extremely serious condition.

This is correct, but not in the way you mean it. We know people can effectively produce no LDL cholesterol in their liver and have positive health impacts - these MR studies are a big part of what drove this entire class of cholesterol medications. And the monoclonal antibody versions of PCSK9 inhibitors have shown basically the same results.

Virtually all human cells can produce cholesterol locally de novo, including your brain.

[_kidlike]

o_O