FDA approves new kind of cholesterol pill
fda.gov
fda.gov
It's quite a beast!
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.
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
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.
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.
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.
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...
Do you have a reference comparing the various factors?
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.
There are mountains of evidence establishing a causal relationship between elevated cholesterol levels and heart disease.
Now, structurally Repatha is straight up more expensive to manufacture and deliver to patients than a peptide like enlicitide, as the former is a biologic. And if a competitor decides to manufacture a biosimilar when Repatha comes off patent in 2030 that could also help cut the price of drugs in this category. But there’s really nothing cheaper than statins, so I would expect insurance agencies to continue to withhold prior authorization.
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.
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
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.
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.
so you solved obesity then! people just need to make better choices! Glad we have you here solving the worlds greatest mysteries
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
Obviously some people still need medication if they have particularly unfortunate genetics.
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)
Advise not callously generalizing your opinion on things like this. It's clear that you either spoke without knowing more, which happens, or you really don't seem to care to know more. I hope you're not in the latter.
There's a strange belief, I believe most born out of morality, that medicine undermines discipline or healthy lifestyle. But it does not, they work in tandem, each making the other stronger.
It is true that taking medication is "easy" - not that easy, though. But easy != evil or immortal. If it's so easy, that's a good thing. It means we can stack it on top of lifestyle changes for very little marginal cost. If you're already working out and eating good, that's great. Go to your cardiologist and see if you're a candidate for statins or hypertension medication.
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.