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?
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?
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.
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.
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.
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.
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.
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.
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.
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)
> 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.
“Proprotein convertases (PPCs) are a family of proteins that activate other proteins. Many proteins are inactive when they are first synthesized, because they contain chains of amino acids that block their activity. Proprotein convertases remove those chains and activate the protein” [1].
It works via the same mechanism as an incredible drug called Repatha (generic name evolocumab), but Repatha is quite expensive, requires refrigeration, and must be injected subcutaneously every two weeks. The news here is that this is administered orally.
Not really a new kind of pharmaceutical, pcsk9 inhibitors have been on the market for a while now. What’s new is that it’s an oral medication rather than an injectable
Hmmm, maybe but I wouldn’t expect a sea change myself. The reason insurance is able to get away with not covering pcsk9 inhibitors is because statins in theory provide a similar benefit for a fraction of the price, and so they can gatekeep access by requiring patients to take statins first before providing prior authorization.
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.
Many people have high cholesterol due to genetics. In these cases even if you ate a 100% perfect diet it would only impact 25% of your cholesterol levels - which any physician would not be satisfied with.
You wouldn't tell someone with diabetes or asthma to just live healthier and avoid their medication. There's nothing wrong with taking a pill, we're not cavemen living off the land.
Eating healthy is a sub-optimal solution. Typically we see the most significant results with lifestyle changes + medical interventions and pharmaceuticals - more than either alone.
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.
Lose weight, yes.
Exercise, yes.
Accept a potentially fatal genetic defect when an option is available? No.
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.
The dietary impact on cholesterol in the blood is surprisingly low. Looking it up, this source says diet can affect 20-30% of your blood levels [1]. I don’t have a great statistic about exercise, but I’d encourage you to question what you think you know — at the very least I’ll claim you’re mistaken about the importance of dietary impacts on cholesterol, which perhaps should give you pause about your other beliefs
Dietary cholesterol has little impact on blood cholesterol. However the post that started this debate mentioned mass loss. And that does have a decent correlation. Go from obese to not obese and the median person's cholesterol will drop quite a bit.
It’s possible the comments have changed, but I see nothing in the thread about mass loss. I do agree about weight though — losing weight is largely diet.
> 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]
eat healthy as in: only once a day and only six days a week. only water for drinking and only fresh stuff to eat, no meat, no eggs, nothing cooked, nothing baked, nothing fried, nothing grilled, nothing processed, no sugar and no salt.
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)
Just do fasting and lose weight. Had high cholesterol and did that lost 20 pounds and my cholesterol went back to normal without any medical intervention
I’m glad that worked for you. That doesn’t work for everyone, and there’s plenty of people with completely healthy weights who eat healthy as well who just have outrageous cholesterol. Any medical interventions that fix genetic conditions seem like a win for me. Even fixing lifestyle issues medically (eg GLP-1s) seem like a win for me.
I have familial hypercholesterolemia and none of that makes any difference. In fact 2 of my siblings and both my daughters have it too. My youngest sister had a stroke at 24 because of 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.
8% body fat, and I can run more in a day than most people do in a week. I’m taking statins. It’s not always as simple as you seem to assume. As others have said, genetics play role, for one.
It's quite a beast!