It's quite a beast!
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...
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
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.
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
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.
Not to mention the gene-therapy version of the same PCSK9 inhibition pathway called VERVE-102 which Eli Lilly is putting through human trials as we speak.
I imagine that stacking the LP(a) antisense therapy with a PCSK9 inhibitor, and/or a statin or Nexlizet would probably lower odds of heart disease death by two to three orders of magnitude. But I guess there isn't solid mortality data to say for sure.
Being a major shift from the good life one should start it with a 7 day water fast. (do I have to say "ask your doctor before embarking"? done)
Do you have the same simplistic ideas about GLP-1's?
[1] https://my.clevelandclinic.org/health/articles/16867-cholest...
> Go from obese to not obese and the median person's cholesterol will drop quite a bit.
This is really interesting, I don’t think I’ve heard that before. Do you have a source you could share?
Edit: this doesn’t necessarily prove you wrong, but this paper argues there’s little correlation between bmi and cholesterol [1]
[1] https://link.springer.com/article/10.1007/s11695-010-0170-7
I'm also not uncommon. They suspect as much of 30% of the population could be like this. There's a lot of ignorance in this thread.
It's one f those things where some people's "I can't help it!" claims are true, but many are not. That doesn't invalidate the first category even though most people in the category are in the latter.
Triglycerides & HDL are affected by weight (tho more triglycerides than anything else), e.g. Wing 2011.
The thread above us discusses neither mass nor weight. Here it is copied in full -- I encourage you to use ctrl-f
> mediumsmart 1 hour ago
> One could eat healthy instead of course but hey, the good life.
> shlant 1 hour ago
> you didn't read the article did you? Or are you actually here to claim that people with hypercholesterolemia just need to eat better?
> Do you have the same simplistic ideas about GLP-1's?
> moi2388 1 hour ago
> For all people? No. For the vast majority of people? Yes. Eat healthy and exercise more
I'm a bit upset that I put in effort to genuinely engage in your claims, and you're not willing to go back and read the thread to confirm claims that _you made_. In fact, you suckered me into re-reading the same thread _for the third time_ looking for some throwaway line I missed about mass or weight. I could just decide that internet discussion doesn't matter, and stop engaging on HN, but I'd rather not do that. Can you please try a bit more?
I'm not going to reply to the Triglycerides & HDL comment without a link. It was your claim initially, and I was nice enough to provide a link with evidence against it, so surely you can do the same in support.
the "link" is obvious, I gave you the cite. If you can't follow it, you need to train your agent better.
And yes, exercising and dieting absolutely reduces the need for these medications.
It also reduces the amount of people who have high cholesterol, although again, in both cases not all
lp(a) is not part of routine blood tests - you probably didn't measure it unless you specifically asked for it.
Diet, statins, etc can't get us in healthy ranges and PCKS9 inhibitors is literally the only thing that moves the needle. I'm on Repatha, one of the injectable inhibitors, statins and Ezetimibe to manage it.
Needless to say I am super happy about this news, especially if it is affordable.
Really hopeful that Verve 102 passes trials and becomes generally available.