Liemandt was on the Peter Attia "The Drive" podcast a couple of days ago discussing this. The episode is 1 hr 37 minutes before you start applying multipliers.
I came to say this. Free episode to listen to.
If you are interested in this it is Nx more cost-effective to listen to Liemandt than to read the adjective laden article.
>Lowering LDL doesn't actually do anything on its own
Is this some sort of weird philosophical statement? Because, of course, it's completely nonsensical, and completely at odds with all data on this file.
Lowering LDL reduces CVD incident rates, with no other interventions. People with genetically low LDL also have lower CVD incident rates. This is extraordinarily well proven.
So it sure seems -- you know, 100% of medical science -- that lowering LDL does "something".
The human body is a complex machine, however, and CVD is multifactorial, and for CVD to develop the current thinking is that you need inflammation and high cholesterol over decades. Inflammation can be caused by things like high blood pressure and the like. But everyone has inflammation to some degree as a facet of living, and the easiest component of that to treat (not just measure) is LDL.
And yes, there is an industry of cholesterol denialists, among whom there are just loads and loads of chiropractors. These clowns have built armies of poorly informed disciples that run to HN to tell us that cholesterol doesn't matter and lowering LDL doesn't do anything.
> People with genetically low LDL also have lower CVD incident rates. This is extraordinarily well proven….. you need inflammation and high cholesterol over decades.
We know that low LDL does not prevent CVD. Therefore we know that you do not need high cholesterol over decades.
It's like saying a flying bullet can't do anything on its own. It is a meaningless statement.
>As I pointed out in another post over 75% of people who have heart attacks have normal LDL.
The actual study authors were advocating for lower LDL guidelines, particularly among the elderly.
A heart attack is the destination, not the journey. What someone's LDL was at admission for a heart attack says literally nothing about their state for the decades before. In actual studies tracking cholesterol, even over a five year period lowering LDL has a potent beneficial effect.
>You’re saying a lot of nonsensical stuff in your comment like high blood pressure causes inflammation , which tells me you are not serious in this discussion
Hypertension can cause endothelial inflammation, leading to blood vessel damage and promoting the release of inflammatory mediators. This is extremely well documented, and it's why getting hypertension under control medically is considered extremely important in the CVD battle. Inflammation and hypertension often are found hand in hand, and there is uncertainty over the cause and the effect, but strangely controlling hypertension alone dramatically reduces inflammation. Weird, right?
>I have zero inflammation
Sorry, but LOL. Not only is that a singular and very narrow test, inflammation is literally just a facet of living. As is oxidization. There isn't a single human alive with "zero inflammation", nor is there anyone that has magically non-odidizing LDL.
If you don’t understand the difference between acute and chronic inflammation, there is no longer any reason to continue this conversation with you. Yes, I apologize because I didn’t specify the difference, but I thought you would be intelligent enough to know the distinction.
Localized foam cell activation and cytokine signaling does not necessarily raise hsCRP yet allows for continue plaque deposition. This is a very well understood mechanism.
No one knowledgeable here is saying that inflammation isn't worth paying attention to, but people acting like because inflammation is also important that LDL does nothing just aren't living in reality.
Your comment about blood pressure actually reveals more about your knowledge here than the person you're replying to.
FDG-PET is a signal we can use to detect tissue inflammation, and we know that higher blood pressure is highly correlated with increased FDG-PET in arterial walls:
Blood pressure results in shear stress to your arteries. This results in several things that amplify Angiotensin II and NF-kB activity, including expoosing adhesion molecules which then results in foam cell activation and cytokine signaling, etc.
It is quite well established that high blood pressure will contribute to increased inflammation.
>But lowering your LDL does not prevent heart disease
Literally one of the most proven truths in medical science is that LDL levels has an almost directly relationship with CVD risk over the long term. Someone with low cholesterol can of course still have CVD, but their odds are much better than someone with high cholesterol. And of course the damage from cholesterol is additive, so the earlier you control LDL, the more of a benefit.
>A new national study has shown that nearly 75 percent of patients hospitalized for a heart attack had cholesterol levels that would indicate they were not at high risk for a cardiovascular event, based on current national cholesterol guidelines.
The damage from high cholesterol happens over decades. Yet the people who actually have heart attacks are often older.
So yes, if gramps spent his life with high cholesterol but now he barely eats and is sedentary, he might have low cholesterol now but that says literally nothing to what you're claiming it does.
Yes, much like wet streets are a high predictor of rain. Or smoke, firefighters and wood are a high predictor of fire. The firefighters are not causing the fire, neither do the wet streets cause rain. This is what people are trying to tell you. If you remove the firefighters only, then you might make it worse. If you do something to cause the firefighters to go away, probably because there isn't a fire anymore, then you did the right thing. The important thing is not to goodhart's law yourself into doing the wrong thing.
This would be a fair analogy if we didn't have studies with a temporal component, but we do. We look at individuals before they get disease then track them over time to see what predicts disease. So we can see, per your analogy, that the fire is there, then the firefighters turn up.
No. They’re saying that damage is cumulative over a lifetime - plaque deposition - so that a point in time snapshot of LDL says little about lifetime exposure. If I live my life with high LDL and only get on statins at 65 I might have low LDL when I have a heart attack but the damage came from the decades of high LDL.
The current guidance from the AHA and NLA is that lower is better for as long as possible.
Lower cholesterol helps but lowering inflammation helps everyone. As I’ve said in another comment over 75% of people who have heart attacks have normal LDL levels.
And lower cholesterol is not without its own risks. You need cholesterol to make hormones and things like CoQ10, which are important for our health. So what’s better? Lowering oxidative stress and inflammation or lowering cholesterol?
LDL levels at admittance do not tell us what their lifetime LDL levels were. But even your own link is arguing for lowering the the number at which we consider LDL levels risky.
PCSK9 inhibitors when coupled with statin therapy have gotten people to ~10 LDL without negative impact in clinical trials. The body is good at producing cholesterol where it needs it - it doesn't pass the blood brain barrier, yet the brain is full of it. It produces it's own, the same as quite a lot of other tissue
For hormones, de novo synthesis of cholesterol is a thing when it comes to steroidgenesis, as well as recycling and re-uptake. PCSK9 inhibitor studies specifically looked at this because of this concern, and found cortisol/aldosterone/testosterone/estrogen/etc. were not impacted by having very lower levels of LDL-C.
The issue with statins and CoQ10 isn't cholesterol - it's the mevalonate pathway. They block a reductase in the pathway and this results in lower serum CoQ10 levels. Data around if this is of any clinical relevance is a mixed bag, but this is easily supplementable if needed, and should not be a reason to not take life saving medication. PCSK9 inhibitors make large dents in LDL but do not impact CoQ10 levels at all because they do not impact the mevalonate pathway.
> If you have normal cholesterol though - we have long known that people with normal cholesterol also have heart attacks.
Just to continue on this line, we also know that people with a genetic disposition for low cholesterol have a significantly lower risk of coronary heart disease than people with ostensibly normal cholesterol levels. It is one of the most proven, obvious correlations (more cholesterol increases the incident of CHD) in medicine.
Some snake-oil merchants, usually pitching a book or supplement, have often tried to muddy the waters by pointing out that someone at death's door often has very low cholesterol (they usually aren't eating, and cancer often "eats" cholesterol and leads to low levels), trying to then extrapolate this out.
These people with genetically low cholesterol, however, have other issues. Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. Many individuals with FHBL develop an abnormal buildup of fats in the livercalled hepatic steatosis or fatty liver.
You have to understand the point which you’re not yet able to put in your head. Yes it is true that lowering cholesterol lowers cardiovascular disease. No one here is disagreeing with that. What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease. I don’t know why this is so hard to understand. Lowering inflammation not only would reduce cardiovascular disease, but also cancer, arthritis and a multitude of other diseases.
> What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease.
interesting idea which I have heard before. However so far as I can tell we don't know if it is true. It seems to fit the evidence that the two are independantly causes of heart attack, when combined it is worse.
maybe someday science will figure this out but it is not easy and so will take a while. Until we do I avoid saying things with high confidence.
Cholesterol is more of a proxy "smoke" or "firefighter" measure than a measurement of the actual fire. It's very much a wet streets cause rain kind of thing.
Artificially eliminating the firefighters doesn't necessarily mean you've solved most of the problem.
Heart disease is a far more complicated problem than "cholesterol" or "cholesterol + inflammation", but humans and patients mentally gravitate to silver bullet thinking, which makes it really hard to work with. One interesting measure I've encountered is the lipid clearance rate, but it costs something like +$20k to measure and is not something a doctor can order from a lab; it's typically only performed in research settings.
This isn't necessarily true. High content of certain cholesterols in the blood does cause heart attacks. It doesn't just indicate it - it actually causes it.
And, we have shown the mechanism of action. Certain cholesterols will build up on artery walls, constraining the flow of blood. When there is too much build up and/or the vessel is too narrow, blood can be constrained too much, causing loss of blood flow and therefore oxygenation. The heart has MANY capillaries and requires a lot of oxygen.
Comments like these just aren't based in reality. LDL levels are not a proxy or a wet streets cause rain. We even have a strong understanding of the mechanisms in which cholesterol causes things like heart attacks, strokes, peripheral arterial disease, etc. etc. etc. Something has to deposit plaque in your arteries.
Yes, from a mechanistic standpoint, inflammation is also an important causal factor. Lp(a) is also an important factor for people that are genetically predisposed to high levels - it also deposits plaque, and is one of the reasons ApoB is recommended. Most people don't have worrisome Lp(a) levels but enough do that we've been missing them, and we now also have good treatments for them - PCKS9 inhibitors reduce it by ~1/3rd, and we have Lp(a) specific medications in phase 3 trials that are even stronger.
But we know that statins work. This is some of the most established science in health. I keep seeing claims in these comments from people stating otherwise, but it just doesn't match reality.
We also know that lowering LDL in and of itself lowers inflammation within the arterial wall, though this isn't necessarily reflected in hsCRP. We know that foam cell activation and cytokine signaling increase inflammation at the site of the plaque, which results in further deposition, and these require ApoB particles be depositing plaque there to begin with. Some PCSK9 inhibitors show zero change in hsCRP results yet still show less localized inflammation - due to the significant reduction in LDL-C and Lp(a) particles.
Lowering inflammation also works for reducing events independent of lowering ApoB particles - colchicine works even though it does nothing there - but if we're really trying to stretch the fire analogy, it's more like LDL and Lp(a) are the years of unmaintained brush and flammable debris in a forest, and inflammation is the strong winds. Both can lead to the spread of fire even without the other, fire can still spread even in the absence of both, but having either and especially having both will greatly increase the risk of the fire continuing to spread.
>These people with genetically low cholesterol, however, have other issues
Neat.
>You have to understand the point which you’re not yet able to put in your head
Nowhere did I ever dismiss other causative inputs. All I did was reply to some probably-listen-to-chiropractor people who sure are trying incredibly hard to downplay cholesterol.
If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
Why don’t you stop your appeal to authority arguments and focus on the facts.
It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
If that is not interesting to you then you have an odd bias. I merely saying that inflammation is the risk factor that matters more than high cholesterol. You can lower cholesterol for someone who has high inflammation and reduce heart disease, but reducing inflammation is more important overall.
>If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
This is such a silly statement I'm not sure where to begin. Plenty of people smoke and drink and don't die of issues related to smoking or drinking, but smoking and drinking are bad for you.
Individual response to things varies. No one reasonable is going to say that because such and such person did X, Y, Z things that we know are bad and didn't have a negative outcome that we must flip the script on if those things are bad are not. Exceptions exist for a wide variety of reasons.
> It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
Calcium score does not tell you how much plaque you have in your arteries - it tells you how much calcified plaque you have in your arteries. This is NOT the same thing. You need a CCTA to tell if you have soft plaque or not.
I'm sorry, but you're just severely misinformed here and spreading all sorts of dangerous misinformation all over the comments here.
> The body does not need cancer, but it does need LDL to transport fats around the body.
Of course the body needs cancer.
Cancer is your own bodies cells. They're essential for you being alive. And, cells with damaged DNA train and hone your immune system.
You have millions of cancer cells in your body right now. Your immune system is killing them as we speak.
If a few happen to slip through, then that's we would say you have cancer. Why might they slip through? Your immune system makes mistakes. Because everything makes mistakes.
> What was it that he did that proved him immune to the ravages of smoking?
Um, nothing?
Is this your first day on Earth? Life is not an algorithm.
Everything is risk, everything is probability. Smoking increases your risk. It doesn't give you anything.
Your HIV and AIDS argument is just fucking stupid. Sorry to be blunt.
Yes, SOME things are A -> B. That is an extremely rare exception to the rule. Extremely. That almost never happens.
Like, if I drive fast, I might die. Might. Its not a garuantee.
I can drive 150 every day and live, or drive 10 and die immediately. That's life. Welcome to risk and probability. That's just how things work.
Having LDL and no heart disease doesn't prove anything to anyone. That doesn't prove LDL doesn't cause heart disease.
It didn't even make sense at the time. It tainted everything under a cloud that the official, accepted truth needed to suppress alternatives to win the battle of minds. It was disastrous, and it is astonishing seeing people (not you, but in these comments) still trying to paint it as a good choice.
It massively amplified the nuts. It brought it to the mainstream.
I'm a bit amazed seeing people still justifying it after all we've learned.
COVID was handled terribly after the first month or so, and hopefully we've learned from that. We're going to endure the negative consequences for years.
And to state my position like the root guy, I'm a progressive, pro-vaccine, medical science believer. I listen to my doctor and am skeptical if not dismissive of the YouTube "wellness" grifters selling scam supplements. I believe in science and research. I thought the worm pill people were sad if not pathetic. Anyone who gets triggered by someone wearing a mask needs to reassess their entire life.
But lockdowns went on way too long. Limits on behaviour went on way too long. Vaccine compliance measures were destructive the moment we knew it had a negligible effect on spread. When platforms of "good intentions" people started silencing the imbeciles, it handed them a megaphone and made the problem much worse.
And now we're living in the consequences. Where we have a worm-addled halfwit directed medicine for his child-rapist pal.
>It massively amplified the nuts. It brought it to the mainstream.
>COVID was handled terribly after the first month or so, and hopefully we've learned from that. We're going to endure the negative consequences for years.
In theory, I agree, kind of.
But also - we were 10+ months into COVID raging in the US before Biden’s administration, the administration that enacted the policies the article is about, came to be. Vaccine production and approval were well under way, brought to fruition in part due to the first Trump administration.
The “nuts” had long been mainstream and amplified before this “silencing” began. Misinformation was rampant and people were spreading it at a quick speed.
Most people I know who ultimately refused the vaccines made up their minds before Biden took office.
> But also - we were 10+ months into COVID raging in the US before Biden’s administration, the administration that enacted the policies the article is about, came to be.
Google makes it very clear that these were choices they made, and were independent of whatever the government was asking. Suggesting these policies are anything other than Google's is lying.
Sure, but I'm not remotely blaming Biden[1]. A lot of tech companies took this on themselves, seeing themselves as arbiters of speech for a better world. Some admin (Trump admin) people might have given them suggestions, but they didn't have to do the strong-arm stuff, and the results weren't remotely helpful.
We already had a pretty strong undercurrent of contrarianism regarding public health already -- it's absolutely endemic on here, for instance, and was long before COVID -- but it mainstreamed it. Before COVID I had a neighbour that would always tell me hushed tones that he knows what's really going on because he's been learning about it on YouTube, etc. It was sad, but he was incredibly rare. Now that's like every other dude.
And over 80% of the US public got the vaccine! If we were to do COVID again, I doubt you'd hit even 40% in the US now. The problem is dramatically worse.
[1] That infamous Zuck interview with Rogan, where Zuck licked Trump's anus to ingratiate himself with the new admin, was amazing in that he kept blaming Biden for things Meta did long before Biden's admin took office or even took shape. Things he did at the urging of the Trump admin pt 1. I still marvel that he could be so astonishingly deceptive and people don't spit in his lying face for it.
This is neat, and I click the little upvote because hyper-optimizations are a delight.
But realistically, is there any real-world situation where one would use this? What niche or industry or need would benefit from this, where the dependency + setup costs are worth it. Strings just seem to be a long-solved non-issue.
This last wave of work was actually triggered by the industry over the last 2 years, as the volume of biological sequence data is growing rapidly and more BioTech and Pharma companies are rushing to scale computational pipelines.
Namely, if you look at DeepMind’s AlphaFold 1 and 2, bulk volume of compute time is spent outside of PyTorch - running sequence alignment. Historically, with BLAST. More recently, in other labs, with some of my code :)
Everyone who enters almost any store is "filmed" with their implicit consent. Cameras are everywhere, and certainly are everywhere in every Australian court as well.
The root comment is precisely right. Deriving data from filmed content -- the illusory private biometric data that we are leaving everywhere, constantly -- is what the purported transgression was.
Seem to be stuck on level 19 (In the Dark), so of course I went to the webdev console for hints where I saw that it was blocked loading Google Ads by my adblocker.
I apologize to the author for blocking ads. It's a legitimately creative and very well executed site.
The UK has had a "brain drain", but it's as much UK citizens as migrants. Economic migrants migrate.
> But also highly paid people have spouses, children, parents and other relatives. Once you are told you barely cleared (very high) criteria, you can be pretty sure your retired parents won't, if ever you need them to move in with you.
Skilled immigration is sold in almost all of the West as a necessary demographic cure. The classic "we're getting older and there is a labour shortage of working age people". The retired parents were never a part of the deal, and are of no interest to almost any Western country. Obvious given that it completely annihilates the justification for bringing people in in the first place.
So if these skilled workers aren't moving to the UK because they can't bring their retired parents, then presumably they aren't also choosing the US, Canada, Germany, etc., given the same situation.
Canada does have a family reunification program but it is not only spectacularly unpopular among the Canadian public and likely to fade away, it allows for a tiny number per year.
US allows unlimited chain migration for parents with short waiting period. Everyone brings their parents/siblings and put them on Medicaid/Obamacare, Section 8, etc right away. Technically sponsor is supposed to cover those benefits (and signs paper about that) but practically gov never tried to recover benefits (literally never).
>There is a 0% chance even one company or person will ever pay this fee
All through Trump's second term, and before, people have said things precisely like this. And here we are. At some point we realize that people just make such confident pronouncements because they think it bends reality towards their hopes.
>Only an act of congress can change visa requirements
It isn't a visa requirement. It's a processing fee. As of midnight no H1B will be considered without the fee. It is very real, and it is absolutely going into effect. Now places like Microsoft are panicking in the information gap currently, but the admin has clarified that it only applies to new H1B applicants.
As to the legal limbo, not only won't there be one, the Supreme Court has rubber stamped just about everything this admin has done.
The guy has both houses of congress, the courts, the DOJ, the full apparatus of government...at this point I find it simply amazing that people still dismiss the reality that he basically does whatever he wants.
The specific quote can be found in a number of media sources-
"Those who are visiting or leaving the country, or visiting India, they don't need to rush back before Sunday or pay the $100,000 fee. $100,000 is only for new and not current existing holders"
EDIT: Weirdly the parent edited in the "unnamed official" bit after I made my comment, then replied as if I'm illiterate.
Regardless, if "unnamed officials" are being cited by every major media source, it's obvious policy, especially given how vague and uncertain so many details of this are.
> It's obvious policy, given how vague and uncertain many details of this are.
" Section 1. Restriction on Entry. (a) Pursuant to sections 212(f) and 215(a) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(f) and 1185(a), the entry into the United States of aliens as nonimmigrants to perform services in a specialty occupation under section 101(a)(15)(H)(i)(b) of the INA, 8 U.S.C. 1101(a)(15)(H)(i)(b), is restricted, except for those aliens whose petitions are accompanied or supplemented by a payment of $100,000 — subject to the exceptions set forth in subsection (c) of this section."
Personally, I do not see anything vague and uncertain about that. I agree that how Trump has been handling things anything and everything is vague and uncertain. But the language of the actual executive order, which in any sane jurisdiction would be the only thing relevant, is pretty clear. Note how it says "restriction on entry", and zero about new applicants.
