Inflammation now predicts heart disease more strongly than cholesterol
empirical.health
empirical.health
> Why? In some ways, cholesterol has become a victim of its own success. We now screen the whole population for high cholesterol, give statins to those with high LDL (or ApoB), and so then the majority of people who end up having heart attacks have lower cholesterol than they would naturally have
In other words, in the study population patients who would have had high LDL were likely to be on statins. The had a lower measured LDL value even though they might still be consuming a poor diet and living an unhealthy lifestyle, for example. Statins don't fix everything about poor diet and lifestyle, but they do help with cholesterol.
So don’t go throwing LDL out yet. It’s still the best measure we have, though you should obviously know that LDL measured while on statins is lower than it would be normally.
The headline, therefore, is somewhat clickbait from a company trying to sell these tests to you outside of your insurance. I recommend checking your insurance to see if the tests would be covered before you go the self-pay route.
Edit to add: If your doctor won't order hs-CRP for some reason, you can order it from sites like privatemdlabs.com for $50 (less if you take their 25% off coupon).
But lowering your LDL does not prevent heart disease. There are many many people with normal LDL who have heart attacks.
In fact, it is the norm. And I can’t imagine how many people are being told. They have no heart disease risk just because their LDL is normal. It’s a crime and it needs to be stopped.
https://www.uclahealth.org/news/release/most-heart-attack-pa...
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.
Wearing a seatbelt does not prevent death in a car accident. There are many people who wear seatbelts who still perish in car accidents.
While you can find a vocal minority who claim cholesterol is not related to heart disease, the best evidence we have is that it is. A lot of the doctors pushing cholesterol denialism are into quacks, such as Uffe Ravnskov who pivoted from denying a link between LDL and CVD into preaching Vitamin C to treat COVID when that hit the news.
However, it's not the only actor in determining heart attack risk.
LDL is used as a predictor because it is easy to measure not because LDL itself causes heart disease. Lowering LDL doesn't actually do anything on its own, because it is just a proxy metric for the underlying problem.
It's more cranky to shutdown discussions by misrepresenting someone's position as "cholesterol denialism". What does that even mean in this context? Finding better predictors is denialism. Great now we just need a ministry of truth.
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.
We know that low LDL does not prevent CVD. Therefore we know that you do not need high cholesterol over decades.
https://www.lipidjournal.com/article/S1933-2874%2825%2900317...
That people can still experience a heat attack even with low LDL does not change that fact. We have very large studies showing the efficacy of lowering LDL.
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.
The reason we offer the tests as cash pay is that it's the only way we can guarantee the price. In the past, when we've gone through insurance, the insurer's "negotiated rate" for the same exact panel comes out to $1,400-$1,500. If the insurer later decides to deny coverage for any of the tests, it's more expensive for the patient.
The $190 price is negotiated to be pretty low. It includes hs-CRP ($59 by itself online), but also the other major heart health biomarkers: ApoB ($69), Lp(a) ($49), A1c ($39), lipid panel ($59), eGFR ($99), other biomarkers, and a video consultation with a doctor to actually explain the results and what to do about them.
For hs-CRP in particular, it's not covered under the ACA as a preventive benefit, so you would usually need to hit your deductible before insurance kicks in at all. (That's assuming they count it as medically necessary at all -- for example, Aetna's current medical policy for hs-CRP requires 2 risk factors, LDL in a specific range, and overall cardiovascular risk to be in a certain range or the claim would simply be denied). It's possible this will change over time as the ACC/AHA recommend universal screening, and I hope it does, but it's a relatively a slow process since it depends on the US Preventive Services Task Force to issue a formal recommendation.
> In the past, when we've gone through insurance, the insurer's "negotiated rate" for the same exact panel comes out to $1,400-$1,500.
hs-CRP is not going to be a $1500 negotiated rate under any insurance these days. No sane insurance company is going to pay that.
I understand that the negotiated rate you're talking about is for an entire panel of many markers, but most of these are not necessary for a quick screen and many would already be covered by an ACA annual checkup.
> It includes hs-CRP ($59 by itself online),
hs-CRP is $50 right now at privatemdlabs.com before the 25% off coupon they're blasting me with in the pop-up. It appears to be in the $40-45 range at a few other direct lab companies.
I checked privatemdlabs.com, and they're asking $249 for a cardiovascular panel that covers the same biomarkers. So I think our pricing compares pretty favorably, especially when you consider that we offer an MD review.
> hs-CRP is not going to be a $1500 negotiated rate under any insurance these days.
The $1500 insurance price is for the $190 panel. We've actually dealt with this exact situation in the last month, since every so often labs will make a mistake when they process the order (we obviously fix these situations). Perhaps the insurance companies aren't sane (a topic for another day), but this is unfortunately how the system works today.
This is one of those weird horrible traps health insurance puts you into. OP may charge insurance 1500$, insurance may only pay 20%. But that now means they have to charge individuals the full 1500$ price.
So honestly, Cudos to the OP for identifying this trap and then moving to just charging a reasonable flat rate.
https://app.hellogoodlabs.com/book-tests
ApoB $12
LP(a) $20
A1c $ 4
Lipid $ 8
eGFR $30 (Under "Cystatin C with Glomerular Filtration Rate, Estimated (eGFR)")
Total: $74
https://curitt.as.me/schedule/7b51cc60/appointment/70269915/...
Cash also has the advantage of the person requesting the test not having to disclose it. For example if you're running the test for getting life insurance and need to lower cholesterol you could use the cash tests for this. Using insurance for this will expose the numbers when you grant access to the insurance company to troll through your records.
If you have normal cholesterol though - we have long known that people with normal cholesterol also have heart attacks. It isn't as common as people who have high cholesterol, but it is still very common for someone normal cholesterol to have a heart attack. We don't really know what to do about this though. This article is saying we should measure inflammation and if found deal with it. Seems reasonable.
What isn't known is if we deal with inflammation will heart attacks go away or if there are more factors. If there are more factors we don't know what they are or if they are worth measuring/treating (though some researchers may have data they are trying to get out here). If dealing with inflammation is good, can we start ignoring cholesterol - another unknown (one for researchers to look into, but the rest of us should for now say no cholesterol is independently important - until data says otherwise)
More in-depth testing would check LDL-P (particle count) and ApoB along with hsCRP.
Though realistically, most people could simply look at their diet and lifestyle and work on improving both before investing in any extra testing. The testing can be useful to catch cases where genetics overwhelm even healthy lifestyles, but in many cases for younger people the testing basically serves as a wake-up call to actually do something about lifestyle and diet problems. It's easier to inspire lifestyle and diet changes when you're staring at bad numbers on the test results and getting a little preview of the consequences of your decisions.
Large bouyant LDL is not associated with CVD risk whereas small dense LDL is.
You can have high HDL, high LDL and low triglycerides. This is a pretty rare pattern, but one where you do not have increase risk of CVD.
In most people, having high LDL is linked to having high small dense LDL and low aounts of large boyant LDL. Hence why LDL is used as a simple risk measure - even though it's wrong.
Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.
As for statins not working well in primary prevention, I'm not sure what you mean - the JUPITER trial showed significant risk reductions for primary prevention, for example.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/ https://pubmed.ncbi.nlm.nih.gov/36779348/
This just simply isn't true and we have massive quantities of data pointing towards protection against major vascular events - even in people that we previously would have considered as having "normal" cholesterol. The NLA and AHA has been revising their guidelines to start getting people on statins sooner and to get levels lower for a reason - it works.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
I got a zero, in other words, no blockage at all. When I reviewed my results with a cardiologist, he basically said, "Some people just have high cholesterol, and it's not a problem. You're probably one of them." I also separately got tested for the type of LDL particles, and mine were primarily composed of big, floaty ones that aren't associated with increased risk (or at least that's what the test result notes said).
I'll do the calcium score every 5 years just to keep tabs on it. But thankfully I didn't start a needless medication regimen.
LDL while clearly not telling the whole story is a great first line defense at population levels because it's easy and cheap (similar to BMI). If you just throw Statins at everybody with high LDL you're going to improve health outcomes, and historically providers and researchers have considered statins to be effectively "free" (both in actual cost and in side effects).
In developed countries where the equipment for this test is readily available, individual patients should absolutely request it even if paying out of pocket, if for nothing more than their own peace of mind.
I'm a layman but I have come to conclude that the AHA's guidelines on when to recommend the CAC test are too conservative. Definitive knowledge of the underlying pathology (or lack thereof) seems like it would be useful both for people with exceptionally high and exceptionally low scores. Even if in a vast majority of cases the treatment plan would be similar (just give them statins) more knowledge seems better on an individual treatment level.
[0] https://www.heart.org/en/health-topics/heart-attack/diagnosi...
Particularly for people below ~45 with significant plaque buildup, calcium scores are often 0 or very low, because all of the plaque is soft.
This is one of the reasons CACs aren't used much in younger people - that plaque hasn't yet calcified.
Soft plaque is the dangerous stuff, too - most statins actually calcify plaque, but this stabilizes it and prevents it from rupturing and the chunks entering the bloodstream.
Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research
https://pubmed.ncbi.nlm.nih.gov/36351849/
A few other more recent papers:
https://pubmed.ncbi.nlm.nih.gov/35498420/
https://www.jacc.org/doi/10.1016/j.jacadv.2024.101109
Note: I'm not a doctor.
Calcium is the end-stage of atherosclerosis. In other words, only advanced atherosclerosis has calcium. The electron beam CT test can, therefore, read zero in people with extensive atherosclerosis, if it is still in the earlier stages. As others note, even early atherosclerosis is bad.
That is why insurance doesn't cover electron beam CT -- it's a crappy test. It provides no reassurance if it's negative, and on a population scale the LDL is far more cost effective and convenient to identify people who need statins.
You might look back at studies from the early statin days, like AFCAPS/TexCAPS, which looked at healthy people like you, whose only risk factor was high cholesterol. The ones who got even the primitive statins of the day lowered their risk of a first coronary event by 37%. That doesn't even tell the whole story, because atherosclerosis can affect any artery in the body. You want your kidneys, eyes, ears, brain, legs, and penis (when present) to work well to the end of your days. Atherosclerosis is a terrible disease.
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.
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.
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.
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.
This is the stupidest thing I've ever heard in my life.
If one person doesn't die from cancer than cancer is not the problem. Fact. Logic.
Not sure if this is your first day on Earth or what, but YES, there's variances in outcomes. Welcome to Earth and being a human.
My grandfather smoked for 70 years and died peacefully. And what?
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.
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.
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.
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.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
We have MR studies on genetics that further reinforce this idea to a huge degree
https://pubmed.ncbi.nlm.nih.gov/28444290/
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.
https://www.frontiersin.org/journals/cardiovascular-medicine...
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.
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.
This is really for real.
MR studies looking at genetics show a decrease in cardiovascular events with lower LDL/Lp(a) levels independent of other factors such as hsCRP
https://pubmed.ncbi.nlm.nih.gov/23083789/ https://www.nejm.org/doi/full/10.1056/NEJMoa1604304 https://journals.plos.org/plosmedicine/article%3Fid%3D10.137...
Lp(a), another plaque depositing particle also has been shown in MR to be an independent risk factor for CVD events regardless of hsCRP
https://europepmc.org/article/med/20032323 https://pmc.ncbi.nlm.nih.gov/articles/PMC5483508/ https://www.nejm.org/doi/full/10.1056/NEJMoa1109034
Decades of plaque accumulation doesn't just go away when you lower your cholesterol.
The question is if people who keep their cholesterol/ApoB low (e.g. Mendellian randomization) have better health outcomes, and the evidence is clear. Lifelong exposure to cholesterol/ApoB mediates atherosclerosis.
I would normally interpret that to mean, lifelong elevated levels of cholesterol/ApoB _decreases_ atherosclerosis.
Is that what you meant?
P1: exposure X is not causally linked to outcome Y if some individuals with lower exposure to X have outcome Y. P2: some individuals with lower exposure to serum cholesterol have heart attacks. C: serum cholesterol is not causally linked to heart attacks.
Because this has some wacky implications:
P1: exposure X is not causally linked to outcome Y if some individuals with lower exposure to X have outcome Y. P2: some individuals with lower exposure to cigarettes have lung cancer. C: smoking is not causally linked to lung cancer.
For example, smokers likely purchase more lighters than non-smokers so there should be some correlation between lighter purchase frequency and lung cancer. But we all know you can't get lung cancer merely from buying lighters.
I’m talking specifically about the claim that because individuals with a low exposure to something don’t necessarily have a given outcome, there is no causal pathway between the exposure and the outcome. It’s not clear to me how what you’ve written speaks to anything regarding that claim.
Not trying to be snarky, I just want to be really clear about the point I’m trying to make here.
I'm not a doctor, but doesn't LDL basically just prevent the body from healing damage to the epithelium, which comes from things like high blood pressure and inflammation? Unless my understanding is wildly off base, it doesn't really make sense that a thing that merely slows down the healing process would be more predictive than the things causing the damage in the first place, given that if you aren't accumulating significant damage then your levels of cholesterol are somewhat moot.
If you're going for more testing, I would definitely suggest the lipofraction.
https://academic.oup.com/eurheartj/article-abstract/46/27/27...
This might dependent on how much you care about false positives and pushing wrong advice to people, but the difference in levels in non Caucasian ethnies in particular is kind of ignored in most directives.
When looking deeper into it, it's a lot more complex than a simple "higher than X is market for Y". For instance:
https://www.ahajournals.org/doi/10.1161/01.atv.19.9.2234
> In conclusion, we have found an ethnic difference in the LDL size distribution, with African Americans having the highest LDL size (“less atherogenic”) and Hispanics having the lowest LDL size; these ethnic differences in LDL size, however, appear to be primarily due to differences in triglyceride and HDL cholesterol among the ethnic groups. Similar variables (triglyceride, HDL cholesterol, insulin resistance, etc) appear to be related to LDL size in these ethnic groups. Last, ethnic differences in LDL size are not consistent with previously reported differences in their risk of CVD or atherosclerosis; in fact, the ethnic differences in LDL size may be opposite the CVD risk differences by ethnic group.
I think LDL is a good biomarker, just not in isolation, and especially not a "one-size fits all" metric for individual humans.
Could you provide a few reputable clinical outcomes studies to support your statements? I was unaware of these risks.
These drugs require constant monitoring by physicians that understand what to look for, that are actively involved in adjusting dosage, for them to be even remotely safe. Muscle atrophy is considered an "uncommon side-effect", but that's just because most studies aren't performed over long enough periods of time. People tend to be kept on statins permanently. And that changes the safety factor considerably, as it does with any medicine taken over years.
My anecdotal evidence is based on multiple family members on these drugs and how even in Norway, with our fairly good healthcare system, it's not monitored sufficiently to avoid issues. There's a lot of strong feelings around statins as is apparent in the other response to my comment, but claims about them being safe except in outlier cases is simply not true.
See the bottom half of my comment at https://news.ycombinator.com/item?id=45446913 - significant muscle damage is exceedingly rare, and ~90% of the muscle pain reported in the RCTs ended up not being related to the statins at all.
Your claims are simply not backed by the data. These are some of the most prescribed and studied drugs on the planet.
These are some of the most studied medicines in human existence. They're not perfect and there are some people that do not tolerate them for one reason or another, but they are a small minority.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/
https://pubmed.ncbi.nlm.nih.gov/36779348/
MR studies on genetics show that LDL and Lp(a) are independent risk factors for cardiovascular events regardless of hsCRP
https://www.nejm.org/doi/full/10.1056/NEJMoa1109034
https://pmc.ncbi.nlm.nih.gov/articles/PMC5483508/
https://europepmc.org/article/med/20032323
https://journals.plos.org/plosmedicine/article%3Fid%3D10.137...
The reputation for bad side effects with statins is basically entirely driven by early generation statins - we've got many that are far better suited for use today than things like lovastatin and similar. Rosuvastatin, pitavastatin, etc. are much less likely to cause any sort of issue for the vast majority of people.
Most of the side effects come at higher dosages, too, but most of the benefit comes from lower dosages. Combo therapy with lower dose statin + ezetimibe or bempadoic acid is becoming more and more popular for this reason.
https://www.lipidjournal.com/article/S1933-2874(25)00317-4/f...
> Based on the Cholesterol Treatment Trialists Collaboration meta-analysis of 27 statin RCT’s (statin vs placebo and high intensity vs moderate intensity statin), for every 1 mmol/L (∼39 mg/dL) reduction in LDL-C there is a corresponding 22% reduction in ASCVD event risk
Even people with "normal" LDL levels see reduction in risk. And people with high LDL levels might end up with a 3-4 nmol/L (or more!) reduction with combo therapy. Meanwhile statins are widely available, very cheap even without insurance, and as previously noted, have excellent side effect/safety/efficacy profiles for modern generations.
Your inaccurate information may be dissuading people who would otherwise get on these medications from doing so when it could literally be the difference between them living and dying. It's irresponsible.
2. Guess what the relative risk of myotoxicity is with statins.
I guess we're on repeat here. U and J shaped curves in observational studies are notorious for being confounded by reverse causality. They did attempt to control for some of the common factors, but cancer often goes undiagnosed, general frailty matches the age group and results in lower LDL levels, and some chronic inflammatory diseases also lower LDL and are not accounted for. CKD often lowers LDL levels due to malnutrition and decreased ability for the production of enzymes involved in lipid breakdown.
But let's dig deeper. Thankfully, we have other studies that help control for all of these factors and give us better evidence.
We have very large meta-analysis of high quality RCTs on statin use such as this one:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
All cause mortality dropped on top of cardiovascular related events and deaths. This is * alot* of data points showing a lack of increased mortality at LDL levels well below the 140 number in your linked study.
Let's go deeper still. The PCSK9 inhibitors are getting us to lower LDL via treatment than ever before:
https://pubmed.ncbi.nlm.nih.gov/36779348/
https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/201...
Evolocumab got LDL down below 20 with better and better CVD related outcomes and no increased in all-cause mortality. Alirocumab taking LDL again, well below the 140 level, decreased all-cause mortality.
But we don't have to stop there. We can look at mendelian randomization studies - while RCTs are the gold standard for determining causal links, well designed MR are far far far superior to observational studies, and particularly when coupled with multiple signals they can be quite good at showing causal links. And that is the case here:
https://pubmed.ncbi.nlm.nih.gov/34729547/
https://pubmed.ncbi.nlm.nih.gov/33704808/
Increasing LDL-C levels = Decreasing lifespan
Observational studies in general are just not good evidence when it comes to all-cause mortality. It's too difficult to control for all of the different confounding factors and the amount of them with J and U shaped curves that do not match RCTs and MRs just shows that. It's the same with bf% - there are observational studies that show 25% bf is lower all-cause mortality than 15%, but there are no proposed mechanisms for that to be the case, no RCTs or MRs that show it to be the case, and for every confounding factor you eliminate the all-cause mortality rate increases at higher bf%.
> 2. Guess what the relative risk of myotoxicity is with statins.
Honestly? Basically not worth mentioning
https://pubmed.ncbi.nlm.nih.gov/36049498/
Blinded RCT/Meta-analysis shows about 11 complaints per 1k patient years, with 90% of them not actually being due to the statin. But because people act like they're common, they mistakenly believe it was the statin, which just reinforces this idea. And that's for muscle pain.
https://www.ahajournals.org/doi/10.1161/atv.0000000000000073
https://academic.oup.com/eurjpc/article-abstract/26/5/512/59...
https://pubmed.ncbi.nlm.nih.gov/15572716/
For actual significant muscle injury? Even lower. 1 or less per 10,000 patient years.
Effectively, you might get one muscle ache per year per 100 people and at most a 1 in 10,000 chance of serious myotoxicity.
The real risk with some statins is increasing your risk of diabetes - some of the older statins impair insulin resistance. But pitavastatin and rosuvastatin actually improve insulin sensitivity, and pravastatin is neutral. Pitavastatin in general has a significantly better side effect profile than other statins in basically every way. It is fairly under-prescribed in the US, though, due to the fact it has just recently become generic, and before that it was difficult to get insurance to cover it with the widespread availability of generic statins that were, honestly, already good enough for the overwhelming majority of use cases.
Additionally, the default treatment option is shifting more and more to combo therapy rather than ramping up statin doses. Most of the beneficial effect of statins comes relatively early on in the dosing curve, and the risk of side effects on the high end of it. You are more and more likely to see a low-dose statin and ezetimibe, which will generally have better LDL-C lowering capability with fewer side effects than a higher dose statin monotherapy. There are also additional options, such as the previously mentioned PCSK9 inhibitors and bempedoic acid that are not available as generics but can be added to therapy if necessary.
Seriously, please stop spreading misinformation about things. You might convince someone who needs a statin to not take one. This could literally be the difference between them dying from ASCVD or not.
I'm quite sure we would still see that cholesterol is useless and that inflammation drives everything.
The OVERWHELMING evidence is that cholesterol is a hugely important causal factor. Overwhelming to the point that we can't do controlled trials for people with CVD risk with cohorts not on a statin in this day and age - it wouldn't pass ethical review, because we have so much data. It is not ethical to withhold lifesaving medication from people when we know it is lifesaving.
The implication here is that the LDL-lowering effect of statins is greater than the CVE-reducing effect of statins. That is, if the statins lower your LDL by 30%, that doesn't bring your risk of heart disease the to the same level as someone who naturally has an identical lower LDL.
If you blocked your arteries before you got on a statin, it can stabilize the plaque and reduce the risk of rupture, reduce the ability for more to form and increase the blockage, and if it gets your LDL low enough, regress some of it, but it's not going to give you the same arteries as someone who never had that level of plaque deposition to begin with.
If true, that would explain the link between inflammation, LDL, and heart disease. It would also imply that the circulating endotoxin is the thing to target. I wonder where all the dead bacteria cell walls are coming from, probably where the dead bacteria are. That, of course, is the gut.
I don't remember the original paper, but I found something that at least explains the theory here.
https://www.sciencedirect.com/science/article/abs/pii/S01406...
Biofilms (for anyone unfamiliar) are a form of coordination used by bacteria. Through simple signaling mechanisms they are able to decide which bacteria are on the outer edge, and which bacteria are safe inside. The guys on the edge become hard and defensive, and protect the inner bacteria from threats (like the immune system).
This also doesn't seem to consider how many people have altered cholesterol status due to genetics. An interesting theory, but if it were proven true, I imagine its effect on public health would be limited to a narrow subset of individuals.
Which given all of these factors are high in society. It's not exactly a surprise. The liver typically gets overloaded and unable to help as well.
This theory as well explains autoimmune and a myriad of other diseases that medicine "dont understand" but that's mainly because this theory is censored. You wont be able to read a page about it on wiki.
This article might be truthful, it might not. But it is absolutely trying to sell you something.
My prediction is that this leads to many secular trends in diet and lifestyle. People have called keto a fad, but to me it looks like what happens when basic human endocrinology and how to manipulate it becomes widely known. I don't expect people to go back to high carb/low fat diets as a weight loss intervention, ever, even once the hype has worn off.
This new news is about research published in the Journal of the American College of Cardiology.
It's definitely not some marketing fad.
Cholesterol -> Coronary plaque -> Dormant bacteria within the plague biofilm is shielded from the immune system and antibiotics. When it ruptures, bacteria is released, sudden death.
Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques https://www.ahajournals.org/doi/10.1161/JAHA.125.041521
>Of the bacteria detected, oral viridans group streptococcal DNA was the most common, being found in 42.1% of coronary plaques and 42.9% of endarterectomies.
High levels of CRP are associated with high levels of oxidative stress.
https://pubmed.ncbi.nlm.nih.gov/15585208/
Inflammation is a synonym for high levels of oxidative stress. Keep your oxidative stress low and you will not get heart disease.
I think we should always be careful when we speak in absolutes. The conclusion from the article:
> This result suggests that oxidative stress may be a determinant of [C-reactive protein] levels and promote pro-atherosclerotic inflammatory processes at the earliest stages of [coronary heart disease] development.
I'm not saying the result is wrong, but I am saying "if you A you will not get B" is over-promising.
if you take this advice literally, you should stop exercising
I've been mostly on a keto diet since 2014, and it is probably the most important health choice I've ever made. At the time I worked in Neurology at a Children's hospital, and a keto diet is one of the treatment options for epilepsy. I talked with the clinical dietician at the time, and asked if these kids were having heart attacks in their 20s. On the contrary, much of the department was on the diet, or a low glycemic diet, as was much of the oncology dept. Obviously, this is an N of 1, and I'm not an MD, but every single aspect of my physiological and mental health has improved over the last 10+ years.
“Dietary Intervention to Reverse Carotid Atherosclerosis” (Circulation, 2010) — participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets; carotid arteries were imaged with 3-D ultrasound cross-sections at baseline and follow-up. After 2 years there was a ~5% regression in carotid vessel-wall volume, with similar regression across all diets (i.e., including the low-carb arm). [1]
Volek et al., 2009 (Metabolism) — 12-week very-low-carb vs low-fat trial; ultrasound of the brachial artery showed improved post-prandial flow-mediated dilation (a marker of endothelial function/inflammation) in the low-carb group. Not carotid 3-D slices, but still vascular imaging with before/after comparisons. [2]
[1] https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.1...
[2] https://lowcarbaction.org/wp-content/uploads/2019/12/Volek-e...
Are you saying losing the waterweight decreased your blood pressure?
AFAIK the water lost was bound to the carbohydrates being stored. It's not in liquid form.
From what I've read[1] the risk with a long-term keto diet is an increase in cholesterol (LDL and total), which can be attributed to lower micronutrient and fiber intake, replaced by more animal-derived foods.
Reducing inflammation is interesting, I'll have to look into it.
Inflammation broadly refers to destructive immune activity (or sometimes any immune activity). If you get a cut, immune cells show up, they kill germs, sometimes they kill somatic cells too. Different cells show up to heal and close the wound. That's all immune activity.
When you need it, it's a net good, but you don't want any of that going on when you don't need it. Increasingly people seem to have more immune activity than they should and it causes cumulative low grade damage. That's the "systemic inflammation" that you've probably heard about.
hs-CRP (high sensitivity C-reactive protein) is a test which seems to be a good biomarker for systemic inflammation, although CRP is just one chemical involved in immune activity. This article is advocating for using that particular biomarker (related to systemic inflammation) to predict heart disease.
The underlying cause of the inflammation usually does produce other symptoms though. Think fatigue, joints, stuff like that. It's one of the many biomarkers that can alert people to change their lifestyle and diet. When they do, they usually feel much better and there will be a reduction in inflammatory markers coincidental with them feeling better.
Can you expand on this? I don't understand.
So for some individuals with a super clean, low cholesterol diet, adding dietary cholesterol would significantly impact their serum cholesterol. But for many (arguably most), it won't make much of a difference, which is one of the reasons DC has moved down in importance in dietary guidelines.
Again, I'm not a doctor. I talk to my doctor and see what others hear from their doctors and am able to make some educated guesses off of that.
https://www.lipidjournal.com/article/S1933-2874%2825%2900317...
I would worry more about HDL than LDL first of all, because HDL is an antioxidant. And it’s about the oxidative stress, which is only another term for inflammation, that we should be concerned about.
So why did I not get heart disease? Everyone else in my family smoked that had heart disease for a much longer period than I did. I only smoked for about five years when I was younger, but everyone else smoked for over 15.
So it wasn’t cholesterol that killed my brother. It was the smoking that caused inflammation on the body that oxidized the cholesterol that killed him.
The positive impact of lowering LDL is some of the strongest science we have on health.
Even from the inflammation standpoint, we know that lowering LDL has a causal effect on lowering inflammation in your arteries - plaque being deposited results in foam cell activation and cytokine signaling which directly increase localized inflammation which can then result in additional plaque deposition.
This is also just extremely well understood mechanistically - to have plaque deposited in your arteries, you have to have something that deposits it. This comes primarily from LDL in most individuals - though Lp(a) is a largely genetically driven carrier of atherogenic particles as well, which is why ApoB is a better measure - and with less LDL there is simply less to be deposited.
The idea that LDL is not a directly causal factor for ASCVD is one goes against mountains of evidence and the consensus of the absolutely overwhelming majority of experts in the field. That is not the same as them saying it is the only causal factor - but people trying to argue that LDL isn't causal have a huge burden of proof on them. This is some of the most studied science in health.
The fact that you don’t care if one person who has high, LDL does not get heart disease is emblematic of the problem in healthcare. If one person who has high, LDL does not get heart disease then high LDL alone does not cause heart disease. There is amounts of evidence that LDL on its own, when it is not oxidized by inflammation, does not cause heart disease is something you’re consistently overlooking.
Again, and I don’t know why I have to repeat this, but I know that Laura LDL decreases cardiovascular disease risk, but that is only because if you have lower amounts of oxidized LDL, then you won’t get heart disease. But what do we want to lower, the LDL, which is needed by the body or the oxidative stress and inflammation which damages the LDL we need for our body?
Inflammation is an important causal factor for sure, and persistent high levels of inflammation will drive even more deposition of plaque.
Your body does not need serum LDL in significant quantities. I’ve commented in this post multiple times with studies that show that even driving LDL down below 20 has no impact to the systems that use LDL that people are concerned about. All of the related organs can do de novo synthesis, make use of HDL instead, etc. People that do not produce LDL at all that ends up in the bloodstream still produce all of their necessary hormones at normal rates, the brain still produces it locally de novo, etc.
No one thinks LDL and Lp(a) are the sole factors in heart disease. We know of plenty that are unrelated - blood pressure, LVH, etc. etc. etc.
But lowering LDL is one of the most powerful and broad spectrum tools we have at our disposal.
Correct. The idea is commonly referred to as "LDL-C Burden"
https://jamanetwork.com/journals/jamacardiology/fullarticle/...
> no solid evidence it can be reversed
We do see good evidence of soft-plaque regression with very low levels of LDL-C, generally in patients undergoing high dose statin therapy or combo therapy.
https://www.jacc.org/doi/10.1016/j.jacc.2021.10.035 https://jamanetwork.com/journals/jama/fullarticle/2584184 https://pmc.ncbi.nlm.nih.gov/articles/PMC7644491/
We don't have any real evidence of effective/widely-applicable treatments to reduce calcified plaque, though.
Weight lifting causes short bursts of inflammation right after training, which is part of the repair process. But in general it is considered very beneficial.
Exercise in moderation is almost always worth it.
The headline makes sense because we've been treating the symptom (high cholesterol) so effectively with statins that for the remaining group of heart attack victims, the real driver is something else entirely: chronic inflammation.
Essentially, high LDL provides the "gunk" for the plaque, but the plaque doesn't become dangerous until inflammation sets in and makes that plaque unstable enough to burst. If your arteries are calm, that cholesterol is less likely to kill you.
The huge win here is the marker: hs-CRP (High-Sensitivity C-Reactive Protein). It's affordable, widely available, and now, officially a critical measure. If your LDL is fine but your hs-CRP is elevated, you have a massive, unaddressed "residual risk."
I hope this pushes doctors to run that test routinely. For us, the message is clear: reducing systemic inflammation through diet, sleep, and stress management is now a non-negotiable part of heart health, even if your lipid panel looks great.
Try meditation? Not the religious stuff, just breathing exercises and trying to clear your mind
That is what I have never been able to figure out. At face value, I believe some people are just 'built' more resilient that others, but that is purely conjecture.
I've tried meditation, but it never really provided any relief. Sure, in the moment, it might reduce stress or a bit, but at least for me, the relief isn't really persistent. If I mediate for 10 minutes, then I get 10 minutes of relief and then after 30 minutes, I am back to where I was before meditating. Same with any other methods I have attempted. How do you reduce stress? How effective are your methods?
Huberman has done a few episodes on it: https://www.hubermanlab.com/episode/tools-for-managing-stres...
https://cancerblog.mayoclinic.org/2025/02/17/want-to-reduce-...
https://health.clevelandclinic.org/anti-inflammatory-diet
https://health.clevelandclinic.org/foods-that-can-cause-infl...
https://www.heartandstroke.ca/articles/the-anti-inflammatory...
https://health.osu.edu/health/general-health/how-fragrances-...
https://pmc.ncbi.nlm.nih.gov/articles/PMC9163252/
https://www.amjmed.com/article/S0002-9343(25)00549-2/abstrac...
> Grains (mainly whole grains): 7-8 servings > 1 slice bread
Who the heck is eating 7-8 slices of bread -- A DAY??? (or the equivalent)... Of a healthy bread that's about 900 calories just from breads...
That's like 2 bowls of cereal for breakfast, 2 sandwiches for lunch, and 2 servings of pasta for dinner, whoa.
https://www.heartandstroke.ca/healthy-living/healthy-eating/...
> People at highest risk are those who work in environments where they’re continuously exposed to fragrances, such the cleaning industry, cosmetics industry or agriculture industry. You also may be at slightly higher risk if you are continuously exposed to fragrance through personal overuse.
I am 5 months into NSAID Gastritis. Would not recommend.
The impact has been significant. Small servings of non-irritating food for months. I’m told the stomach lining does heal given time, and my symptoms are better now than a few months ago. The post I originally replied to sounded like a recommendation to take Aspirin speculatively as a preventative, which is exactly the mistake I made. Gastro resistant tablets might have helped, but the general advice is to be very careful with NSAIDs on the stomach (although I still use topical Ibuprofen gel when needed).
also they list a big list of drugs that are in various stages
I don't even know. But exercise is the god-tier reigning champion of all things health. You can count on it pretty reliably to show up as a positive effect source in any health study.
"Just exercise" should be a meme at this point.
To get a statin you have to go to the doctor, get a blood test, get a prescription for the statin, and start taking it, get blood retested, adjust dose (possibly), etc. Then you have to go to the pharmacy, pay for it and take it every single day.
To exercise you literally have to walk for 30 minutes. That's it.
If you have high cholesterol, you probably have to change your diet to put any real dent in it, like reduce consumption of your favorite foods.
Meanwhile a low dose statin can drop your cholesterol by 30%.
For the record adding a statin reduced my (genetically very high) cholesterol by over 50%, and I will almost certainly take it for the rest of my life. Diet and exercise changes led me to lose over 80lbs, required 0 doctor visits, cost $0, and has completely changed my life and my likely health trajectory.
So yes take statins, but no statins aren't 'easy' unless you are very well integrated into a health care system and actively having checkups where your cholesterol levels are being checked and reviewed, which is only true of a very low % of people in the US, even those with gold plated healthcare coverage.
It might for all-cause mortality, but it is unlikely to reduce ASCVD mortality more than a statin, or statin + ezetimibe would. Even if your high LDL isn't genetic, once you've done the damage to your arteries, it is basically going to stay there, and treatment targets for preventing further damage at that point (or some regression, if you get really aggressive with combo therapy and get down below 50) aren't often possible with lifestyle changes alone.
People at risk for ASCVD should also realistically just be doing both. It shouldn't be an either/or.
All of this is fine, having your response take the shape of a rebuttal was silly.
Let's trace the context:
The very first comment is talking about lowering inflammation in relation to this article. This is within the context of ASCVD
The next comment is saying to exercise. This is in answer to someone asking about inflammation in context of ASCVD.
The next comment is saying this is harder than taking a pill. Still in context of ASCVD.
Then you comment saying it's not that hard in comparison to getting a statin. Which, again, is treating for ASCVD.
The next comment is talking specifically about how walking will not be enough to impact your cholesterol. Again, ASCVD.
Then you switch the goalposts to talking about all-cause mortality when the entire rest of the conversation has been about ASCVD.
Then I reply saying yeah sure exercise impacts a whole lot more causes of mortality but again reiterate that suggesting it as a solution in a conversation about ASCVD does not make much sense. The people in this situation are worried about ASCVD in specific - their remedial actions should focus on ASCVD. Your commentary also further restricts things by talking about if you previously weren't exercising at all, but plenty of people that DO exercise regularly and walk 30 minutes a day are still at risk for ASCVD because exercise does very little to reduce cholesterol without additional lifestyle modifications around diet, and even then, it is unlikely to get you to modern treatment targets.
Who is the person here who went against all the prior context? Not me.
----
But if you're going to say I'm rebutting your points, I suppose I might as well actually do that.
First, we can just talk about lifestyle changes in general - we know they don't work for most people. Not in the sense that if someone adheres to them they don't function, but that most people don't adhere to them. People aren't awesome about adhering to medications either, but they're a lot better than they are about overhauling their diet and exercise regimen. Countless studies here, very obvious evidence when looking at drugs like GLP-1s and the impact they're having on weight loss vs. lifestyle changes, etc. I can dig up studies here if you really want, but I do feel like this should be pretty self-evident.
Next, let's look at your strange claim about how statins are only easy for a low % of people in the US, despite the fact that over 1/3rd of the adults in the US take statins. Atorvastatin is literally the most prescribed drug in America.
https://www.sciencedirect.com/science/article/pii/S131901642...
> After 2013, the number of individuals who used statins increased 149% from 37 million in 2012–2013 period to 92 million users in 2018–2019.
92m statin users in the US as of 2019, almost exclusively used in adults. 260ish million adults in the US as of 2022. If a third of all adults are using them, it can't be that hard, either.
How many adult Americans get the CDC recommended 150 minutes a week of moderate aerobic activity, less than the 210 you are saying is easier than statins? 46%. I suspect that number drops if you increase the amount of aerobic activity by more than a third, but there's not data on that specific number of 30 minutes a day that I can find. And the CDC, for all cause mortality, says you really should add in some resistance training as well, which brings the number down to 23%. And the sort of people doing this regularly also tend to be people that are more health conscious, have better diets, etc., too, which means they were already less likely to need statins. For people that don't live that lifestyle, they've not lived it for a reason - and changing to someone that does live that lifestyle is a significant shift.
https://www.cdc.gov/nchs/products/databriefs/db443.htm
I'm not saying exercising is that hard - I hit 5 hours a week most weeks, and more some weeks. I also spent a decade or so with an LDL sitting in the 70-110 range, which we know means I was depositing plaque, despite that being in range to just barely out of range on most lab reports. So I take a combo therapy to get mine down to <40 to hopefully get some regression and to stabilize what won't regress. Anecdotally, I can tell you what's easier between the two for me to do - taking the pills. They show up on my doorstep, I spend 5 minutes each Sunday putting them in pill organizers, and 30 seconds each morning taking them. Bloodwork related to the ASCVD stuff? Once a year. Insurance covers it all, but even if it didn't, I can get a 90 day supply of 20mg Rosuvastatin for $8 and ezetimibe for $9 from CostPlus and similar prices from goodrx, and a lipid panel from jasonhealth is $10 (though I think they have a draw fee which is probably $25ish). But this stuff is all generic and so cheap you don't need great insurance to cover it - none of this requires a preauth. You're really unlikely to be fighting your insurance on any of this even with a pretty mediocre plan.
So your entire argument that a lifestyle change of walking for 30 minutes a day every day is significantly easier (or even not-so-significantly) vs. a couple of hours a year of doctors visits and labwork and then popping one or two pills daily is just pretty fundamentally flawed - it doesn't match the numbers even in the absolute and even less when you consider the success rate of lifestyle changes. The picture you paint of the ability to get on a statin as difficult even among those with "gold plated insurance" doesn't make sense. The only thing that does is that yes, going from no exercise to regular exercise will lower all-cause mortality. But the whole conversation had been about ASCVD until that point, and even the rest of your comments in both cases were discussing statins, which are again, almost entirely focused on ASCVD.
It's only hard because we make it hard.
There's people that live even closer that drive their kids to school. One of them lives literally 19 houses down the street from it.
I also have a rule where if I can go somewhere within 20 minutes on a bike, I'm taking my bike. Most places I go fall under this rule, and I live in what most would call a suburban hellscape.
My wife used to drive to work. Driving took longer than walking. But she still drove.
I think it's less about easy vs hard and more about the culture around driving in the US.
I tried biking to work for a while - 13 miles. During summer/fall, it was pretty nice, I'd go early in the morning, shower at the gym, and then bike home. 2 workouts a day when the weather was fair.
The sweaty part, you'll get less sweaty as you get more in shape, both exerting less and retaining heat less efficiently due to lower BMI. But - you'll probably never not be sweaty if the distance is anything significant like, say, 13 miles.
Let's talk about colder climates. I was a consultant for a few years, and got to travel all over. I recall visiting Calgary in the winter, and some maniac dev manager biked to work every day, rain, snow or shine. 6 miles he said (helpfully translating units for me).
[0] I heard this claim a long time ago, but according to Wikipedia (https://en.wikipedia.org/wiki/Plato#Life) it's apocryphal. The Talk page has a decent argument for it not being the case.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7498668/
What lowers oxidative stress is nutrition, specifically selenium, vitamin C, manganese, zinc, and copper.
https://www.derekthompson.org/p/why-does-it-seem-like-glp-1-... (Control-F "Theory 2: GLP-1 is a miraculous “moderation molecule,” and it has docking portals all throughout the body that reduce inflammation.")
https://www.health.harvard.edu/diseases-and-conditions/do-gl...
Not sitting a lot (more than 1 hour at a time), walking or cycling everywhere, not eating a kot of sugar/refined carbs..
There is no free lunch or magic bullet (yet) to health. We're all going to die.
tl;dr: Exercise, sleep, and diet. Plus a zillion different supplements and medicines as adjuncts to a healthy lifestyle.
First, consider what inflammation is. It's fundamentally an immune response designed to attack unhealthy tissue and to facilitate repair of healthy tissue - the effects of inflammation are largely driven by cytokines like TNF-alpha (which is responsible for killing unhealthy cells and recruiting immune cells), IL-1 (which recruits immune cells), and IL-6 (which drives cRP production - the biomarker that you usually look for to gauge systemic inflammation). The production of these is mediated by nuclear factor kappa B (NF-kB).
Other major factors are things like reactive oxygen species (or "free radicals"), which can oxidize all sorts of things in the body and cause damage (which is good when the thing being damaged is a pathogen or damaged cell, bad when it's healthy tissue). Damaged tissue provokes immune responses.
So, if you want to "reduce inflammation", you want to:
1. Reduce stimuli or downregulate processes which are causing the production of inflammatory cytokines
2. Upregulate the production of anti-inflammatory cytokines
3. Ensure sufficient antioxidant capacity to deal with ROS production and oxidative stress
If you've got a chronic illness or autoimmune disorder, you're dealing with inflammation just because your "make immune defenses" signals are stuck on. But you can also have chronic inflammation through too much fat (adipose tissue is an endocrine organ!), environmental or diet factors, or just behaviors which result in an imbalance between pro- and anti-inflammatory responses in the body (for example: smoking induces consistent tissue damage, which drives immune responses).
Exercise upregulates production of anti-inflammatory cytokines and improves mitochondrial efficiency, which results in less ROS production during cellular respiration. Sugar surges cause elevated ROS production, and chronically-elevated blood glucose results in insulin resistance, which promotes inflammatory cytokine production. Lipopolysaccharides from gut bacteria in the bloodstream stimulate immune responses. Insufficient sleep upregulates NF-kB directly, but also contributes to dysfunction of other systems which can upregulate NF-kB.
If you're sleeping plenty, eating well, and exercising, and you don't have a chronic health condition, your inflammation levels are probably pretty good. But you can generally further reduce them with supplementation of things like:
* Omega-3 fatty acids (which compete with omega-6 fatty acids - "seed oils", which produce inflammatory prostaglandins) - this is why your doctor wants you to take fish oil
* Turmeric, resveratrol, and green tea extracts (which contain compounds which inhibit NF-kB and are ROS scavengers),
* Vitamin D (which inhibits cytokine production and supports your natural antioxidant systems)
* NAC, which replenishes glutathione (the primary driver of the body's antioxidant systems)
There are medications, of course, like your regular old aspirin and ibuprofen, which reduce prostoglandin production (which is one upstream of NF-kB), corticosteroids (which block NF-kB), as well as more exotic entries such as GLP-1 peptides (which, among other things, improve insulin sensitivty and reduce adipose tissue, which results in reduced systemic inflammation) or BPC-157 peptides (which acutely inhibit NF-kB, upregulate antioxidant enzymes, and help regulate nitrous oxide, which is how they can help heal NSAID-induced leisons).
This is by no means comprehensive - there are plenty more mechanisms and interventions to explore - but it should be a pretty good clue as to why "diet and exercise" are standard health advice. You don't want to turn off your inflammation responses - they're responsible for taking out pathogens, killing tumors and maintaining a healthy body - but you don't want them chronically upregulated, either.
Novo Nordisk purchased Corvidia Therapeutics in 2020 [1] for their IL-6 antibody and will read out the first of three Phase 3's in 2026 [2]. Their programs, however, are focused on individuals with higher risk factors like chronic kidney disease (2026 topline), a couple kinds of heart failure (2027), and a prior myocardial infarction (heart attack; 2027). These trials notably are on top of "standard of care" existing therapies, so they're looking for additional benefit beyond what is commonly sought, like LDL reduction (highlighted in other comments).
Novartis recently announced an intended acquisition of Tourmaline Bio for their IL-6 antibody [3]. So attention to the biological target is heating up.
Another target mentioned in the comments is Lp(a). Genetic studies suggest a heightened risk of cardiovascular disease. Therapeutics aimed at reducing Lp(a) levels are being explored separate from IL-6 for a similar end goal of avoiding cardiovascular events (i.e. heart attacks, death).
Novartis will read out a Phase 3 of an Lp(a) reducing therapeutic in the first half of 2026 [4]. Amgen will likely read out theirs likely sometime thereafter [5]. These have been a long time coming: Amgen in-licensed their asset from Arrowhead in 2016 [6], Novartis in-licensed their asset from Ionis/Akcea in 2017 [7].
If any of these work, there's a chance that they'd be explored in patients with less pronounced risk than the original studies in these Phase 3's. Amgen has already announced an intent to explore their Lp(a) drug in a Phase 3 with participants with elevated Lp(a) at "high risk" for a first cardiovascular event in 2H25/1H26.
[1] https://ml-eu.globenewswire.com/Resource/Download/e7e162e5-a... [2] Page 113 - https://cdn.ipaper.io/iPaper/Files/ffd0326c-1fa6-41e5-a82d-0... Page 225 - https://investor.novonordisk.com/q2presentation2025/?page=22... [3] https://ir.tourmalinebio.com/news-releases/news-release-deta... [4] https://ir.ionis.com/static-files/66c5e90a-3651-480d-a596-1c..., https://clinicaltrials.gov/study/NCT04023552 [5] https://clinicaltrials.gov/study/NCT05581303?rank=1, Page 15 - https://investors.amgen.com/static-files/27fcb898-9cee-48db-... [6] https://www.amgen.com/newsroom/press-releases/2016/09/amgen-... [7] https://ir.ionis.com/news-releases/news-release-details/ioni...
And avoiding putting stuff in your body that makes your immune system react like air pollution, microplastics, hyper processed foods
Good luck avoiding either of those. For the first one, if you live in a heavily industrialized or urban area and can't just leave for X reasons, should you perhaps breathe less?
As for microplastics, from all I've read about them, they're now in nearly everything and many modern humans who haven't spent their lives living and eating/drinking entirely off the land in the deep remote country are unavoidably saturated with them to the point where (need to find the source again) the average modern adult human in the developed world has something like a teaspoon worth of microplastic inside their body. They've become essentially impossible to avoid if you eat or consume any modern food item.
I exercise an hour a day (resistance + cardio), eat a diet of nothing but meat + vegetables + yogurt.
Will post my lipids below. Sometimes you just get fucked by life.
https://i.imgur.com/r0nfUo3.png
For those that won't view the image:
LDL: 72
HDL: 23
Triglycerides: 49
Apo(B): 85Was a hypothetical cause ever suggested?
Very genetically predisposed to cardiac events unfortunately
My money is on it being within normal limits.
> Curious what drives these events in cases such as yours.
Good luck to you, hope you keep on top of it!
If I'm being extra charitable, this kind of test might show up an elevated Lp(a) level, which is a risk factor. At which point you would want to consult a qualified physician, not rely on a single blood test interpreted by an algorithm.
The panel from the company above (I’m a co-founder) includes a review with an MD (not just an algorithm).
It specifically measures carotenoids through the optical heart rate sensor -- you mostly get carotenoids from eating vegetables, and they do reduce inflammation.
But Skyrizi has been way more effective so far and had almost no side effects, knock on wood. I say "almost" because I've had some different, milder skin infections (mostly seborrheic dermatitis) that I can't say for certain were caused/exacerbated by Skyrizi, but either way it's miles better than active Crohn's disease so I'm not complaining!
Obviously it depends on your particular condition and the drug in question, but my take is that unmediated immune dysfunction is worse for you 99% of the time than the side effects of any biologics used to treat it. (That calculus changes if we're talking about non-biologic options like methotrexate or steroids though, lol.) For example, when I was on TNF inhibitors, those come with a black box warning about how you might have a slightly higher risk of developing cancer while taking them... but that risk is still far lower than the inherent cancer risk from unchecked intestinal inflammation. Plus the fact that drug-induced cancer is (1) not a guarantee and (2) something you have a chance of beating, whereas choosing to suffer without effective IBD treatment would doom you to certain suffering and a very high likelihood of permanent bowel damage, etc.
Different drugs just have very different impacts, too. Even though I took Remicade and Skyrizi to treat the same condition, the latter is an older drug with a shotgun-ish approach to immune suppression (even more so than Humira); Skyrizi is much newer and more like a sniper rifle. Newer isn't always better, but monoclonal antibodies in particular have come a long way even in the past decade or so, and I'm optimistic they're only gonna get better and better. I actually just read this the other day, which you might find interesting! https://worksinprogress.co/issue/how-to-make-an-antibody/
I'm prone to weird skin infections already, so no telling what would happen to me lol. Then again, my AI condition is some psoriatic variant. However, I technically classify in the mild category -- body surface < 2%. Topicals don't really work well for me considering my variant kind of look like mild chicken pox. I'm in a weird camp because treatments seem to have very little effect, yet I am not truly severe enough to warrant biologics. My doctor essentially gave me an offer, and her words were near verbatim, "You can keep using topicals and whatnot and never be completely clear, or take Skyrizi, be 100% clear, and stop wasting your time."
I chose the first option as dumb as it may be. Worrying might be my main personality trait at this point in life, and something about the biologics do not sit right with me. I am less worried about the cancers and more about the increased risk of infections. I suppose one detail I left out prior was that my entire condition was triggered after an infection 10 years ago. Plus, with all the ever growing research surrounding Long COVID, how Shingles vaccines seem to correlate with a reduction in dementia, etc. I am not certain infections are something that should just be casually dismissed as a benefit that is worth the risk. Though, I believe this only for my situation. You have to understand that my condition causes me zero functional impairments nor does it prevent me from doing anything I want to do in life. I imagine a vast majority of people on biologics could not say that same (without biologics).
That article was fascinating! Thank you for sharing it.
(For your current situation, you might also want to look into other biologics like Dupixent or Xolair, which can also help with skin conditions have different effects/trade-offs that might be more within your risk tolerance!)
2/3 of my biggest fears in life lol. The other being some form of dementia. I have had worsening digestive issues, albeit this was something I had prior to the psoriasis disease.
Honestly, I keep trying to hold out for as long as I can -- not that I am under really any pressure. With each year that passes, better treatments come out. So, if I can make it a decade longer, then who knows what treatments will look like then?
Do the injections hurt? I am not afraid of shots, but I do not know if I can give myself one. I'd need like 3 shots of whiskey and a rag to bite down on, and then I might be able to do it. Hope alcohol doesn't interact with the medications (I don't drink much normally).
I will also say there's truly never been a better time to be diagnosed with an autoimmune condition, given the quality and number of treatments available these days. For Crohn's and colitis in particular, if you catch it early enough and find a treatment that works for you, I believe it's possible to prevent the worst of the permanent damage so long as you remain in remission or mild-at-worst inflammation. Compare that to twenty years ago when there were only a few treatment options, which made it much harder to get in remission, which increased your odds of needing surgery or similar.
Burying the lede a little, here. The ACC has decided on a standard way to measure inflammation, which decades ago was a centerpiece of some very woo-woo "following the squizledoff diet will decrease your gomperblorp"-style health 'advice'. "Systemic inflammation" was a very tricky physiological parameter to nail down.
https://zellavie.ch/wp-content/uploads/2020/06/Nature-Medici...
You only have to read up on the history of how the cholesterol hypothesis came about to realize the science behind it was poorly defined, poorly tested, and arguably counterfeited as data was cherry picked.
We have converging evidence from in vitro studies, cohort studies, mendelian randomisation and randomised controlled trials all showing that lower ApoB/LDL results in reduced CVD and mortality.
What would it take to convince you that the cholesterol hypothesis is more likely true than false, if not all the above?
Presumably one of “time spent working in asbestos factories” and “cigarette pack years” is more predictive of lung cancer incidence than the other. Does this being the case mean that either smoking or inhaling asbestos particles isn’t causally implicated in lung cancer? If the answer is “no”, then presumably you can see why the inference you’re making is faulty.
I don't think anyone would argue that inflammation is a cause of heart disease. Inflammation is always a body's response to some underlying condition. The cholesterol hypothesis argues that dietary cholesterol is the important factor causing heart disease.
My argument specifically is not that inflammation causes heart disease and dietary cholesterol does not. That seems to be what you were arguing against.
> If the data here is correct and inflammation is a better indicator of heart disease than cholesterol levels, it should raise questions whether cholesterol levels are correlative rather than causal.
But, as with the asbestos and smoking example, I don’t think an argument with this structure is valid. What I’m arguing against is your claim that the existence of one exposure/outcome relationship with a stronger association entails casting doubt on other exposures’ relationship with the same outcome.
Does that make sense, and do you have a good argument as to why we should believe that it casts doubt?
We know from studies that if you get your LDL low enough, such as <50 (and don't have high Lp(a)), you not only see plaque stop being deposited, you even see regression of existing soft plaque, regardless of other factors like inflammation. MR studies show people that don't produce LDL/Lp(a) in significant quantities basically just don't die of atherosclerosis related heart-disease.
We have medications that can lower systemic inflammation, but local inflammation can still allow for plaque deposition in the presence of high LDL/Lp(a) and can be caused by a wide variety of things, and then plaque deposition itself causes more local inflammation via foam cells and cytokines.
We have medications today that let us drive LDL down to extremely low levels - combo statin/pcsk9 inhibitors, statin/ezetimibe/bempedoic acid, etc. - and the current evidence points towards doing this as being extremely efficacious for prevent atherosclerosis without significant side effects. Lp(a) isn't as great of a story yet - the pcsk9 inhibitors do make a ~30% dent in it, but we have other meds in phase 3 trials right now that are more like 80-90%. We're going to be able to remove the vast majority of atherogenic particles from the bloodstream well before we have any way to prevent all of the potential ways your endothelial walls can be inflamed (if that will ever even be possible.)
Why in the world can't there be multiple causative factors?
We have a mountain of evidence that LDL-C/Lp(a) are causal regardless of hsCRP levels, both from medications that don't lower hsCRP, LDL-C/Lp(a) are direct causal factors for local inflammation themselves, and MR genetic studies show them as independent risk factors as well.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/
https://pubmed.ncbi.nlm.nih.gov/36779348/
https://www.nejm.org/doi/full/10.1056/NEJMoa1109034
https://pmc.ncbi.nlm.nih.gov/articles/PMC5483508/
https://europepmc.org/article/med/20032323
https://journals.plos.org/plosmedicine/article%3Fid%3D10.137...
The cholesterol hypothesis never left that room on the table though. The argument made was that dietary cholesterol was the cause of heart disease and that we could measure current risk levels via blood tests, with later additions of related tests meant to measure cholesterol and plaque build up.
My point wasn't that cholesterol is entirely unrelated to heart disease. I was only showing appreciation that research questioning cholesterol's outsized focus in heart disease is finally gaining traction. I'm actually a but surprised that appreciation was controversial, science is always better off when we give space for alternative explanations.
We also know that very low levels of LDL, even in the presence of inflammation, will regress soft plaque build up, and from MVMR and 2x2 factorial MR studies that populations with genetically low LDL/Lp(a) levels see hugely reduced CVD risk regardless of other variables.
We've got more and more science around PCSK9 inhibitors that showing evidence that there are no health risks in dropping ApoB levels to near 0. We have additional treatments in phase 3 trials that are showing 80%+ reductions in Lp(a) as well, so soon even people with the unlucky Lp(a) genetics will be able to get their ApoB numbers down to extremely minimal numbers.
Without the ability to completely remove inflammation or stress to arterial walls, LDL can deposit, increase foam cell activation and cytokine signaling, and then cause more localized inflammation which then repeats the process.
Treating inflammation, both systemic and local, of course reduces the ability to for plaque to deposit. But if we have no or very few atherogenic particles in our bloodstream to begin with, there's nothing to deposit. It's not been practical to drop LDL to that level until PCSK9 inhibitors came into existence, but it is now.
Many experts are arguing that just like blood pressure (which was recently revised down again, to <120/<80 as normal, 120/80+ pre-hypertensive, etc. etc.) we have set the acceptable levels of LDL too high and that targets should be lower, and treatment starting earlier.
There's of course a variety of other health impacts from having significant levels of inflammation - so treating it makes a lot of sense too. Not saying we shouldn't. But when we can basically ignore inflammation at a low enough ApoB because plaque is actively regressing, it makes it hard to argue that the focus is outsized, at least when it comes to atherosclerosis.
(I've got 20+ reference links to RCTs, multiple MR types, large meta analysis, study reviews, etc. that I feel like I've reposted like 500 times in here so I apologize for not doing so yet again, but if you check my recent comments you can find supporting data for all of the claims I've made.)
MR studies have shown very little evidence higher HDL does much, if anything, to prevent CVD or serious adverse events.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
CETP inhibitors keep getting abandoned because they're not seeing improvement in cardiovascular outcomes, despite significant increases in HDL. One of the few that did show improvements in outcomes, anacetrapib, appears to have done it through a more significant reduction in LDL than the others, but even then, it was not promising enough for Merck to continue development, and it has since been abandoned.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5756107
The current CETP inhibitors still in development such as obicetrapib are focused primarily on their ability to lower LDL rather than raise HDL.
MVMR studies are also quite clear that absolute atherogenic particle count - primarily LDL-C/Lp(a) - are far more important than HDL #s. ApoB, which calculates the total of your atherogenic particles is probably the best marker we have.
https://journals.plos.org/plosmedicine/article%3Fid%3D10.137...
For a while we thought looking at sdLDL in particular might be a more specific signal to look at, since these are more atherogenic than larger LDL particles, but we've found they correlate so strongly in the vast majority of cases that it's really only something that matters as an exception rather than the rule
Risk being higher when Tg is more than 2x HDL in adult men. Even then, I'm not sure that medication as intervention is always the right answer vs lifestyle changes, which are of course harder.
https://eas-society.org/wp-content/uploads/2022/11/2019_dysl...
https://www.jacc.org/doi/10.1016/j.jacc.2022.07.006
https://www.lipidjournal.com/article/S1933-2874(25)00317-4/f...
https://www.ahajournals.org/doi/10.1161/cir.0000000000000625
TG/HDL ratio is useful in one place, though - it's a reasonably good screen for insulin resistance if your labwork doesn't include more direct measures.
As for lifestyle intervention vs. medication - lifestyle changes are maybe enough if you're young. Like, in your early to mid 20s young. Plaque is a lifetime accumulation thing, and it's not like it waits until you're old to start accumulating, and while soft plaque can regress, it takes very low levels of LDL - sub 50, and similar with Lp(a). Not sure what the target is for cumulative ApoB. By the time you're diagnosed with ASCVD the treatment target for your atherogenic particles is lower than you can achieve with lifestyle changes alone, and requires medication. And there's a lot of data, such as was examined for the latest NLA recommendations that treatment targets should probably be even lower and people on statins or other therapy for them even sooner. We've relied on CAC as an indicator for a long time because they're relatively cheap and easy in comparison to things that actually pick up soft plaque, but soft plaque can and does still block your artery and can rupture, and even most people with dangerous levels of soft plaque will score a 0 on a CAC up until their 40s or 50s.
We also just know that lifestyle changes just don't work. People don't do them. So even if you're otherwise a candidate because of age, etc., the doctor should still almost certainly be recommending medication - and then if the patient really believes they can make the change, they can decline.
The argument, as I recall, is that the inflammation causes your body to want to treat the inflamed area and when coupled with cholesterol causes "cholesterol Band-Aids" to be plastered all over your arteries. The argument is that if you remove the inflammation, the cholesterol is not important because it's not trying to be made into a Band-Aid.
TLDR: women who would otherwise be missed by current algorithms might be picked up by this inflammatory marker (hs-CRP)
Lp(a) is a largely distinct risk factor from “ordinary” cholesterol and cannot be changed by diet or exercise. Survey papers show practically no effective treatment (statins help all cause mortality in patients but do not lower lp(a)). There are two (iirc) ongoing trials for new, effective drugs. But those are not available yet and will probably be prohibitively expensive, going by the advertisements that the companies run.
So yeah, get an Lp(a) test once (it doesn’t vary too much over time) and reduce your other risk factors, but don’t put too much hope into an easy solution to this specific cause yet.
edit: found the two papers that were a good read:
Kamstrup, P. R. (2021). Lipoprotein(a) and Cardiovascular Disease. Clinical Chemistry, 67(1), 154–166. https://doi.org/10.1093/clinchem/hvaa247
Schwartz, G. G., & Ballantyne, C. M. (2022). Existing and emerging strategies to lower Lipoprotein(a). Atherosclerosis, 349, 110–122. https://doi.org/10.1016/j.atherosclerosis.2022.04.020
https://medium.com/@petilon/cholesterol-and-statins-e7d9d8ee...
> Of 1000 people treated with a statin for five years, 18 would avoid a major CVD event which compares well with other treatments used for preventing cardiovascular disease. Taking statins did not increase the risk of serious adverse effects such as cancer. Statins are likely to be cost-effective in primary prevention.
What the BMJ has to say on this very topic of statins:
https://www.bmj.com/campaign/statins-open-data
So no settled science here.
And remember that the largest ever study on saturated fat and cholesterol lowering was just not published by their original author because it didn't proove their hypothesis.
Lowering cholesterol lowers the amount of oxidized cholesterol that is caused from inflammation. The fact is is that in inflammation is the fundamental disorder, not high cholesterol on its own.
pubmed.ncbi.nlm.nih.gov/18625445/
Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis.
https://www.frontiersin.org/journals/cardiovascular-medicine...
The point of the original article is we should be focusing more on lowering oxidative stress (inflammation) instead of focusing on lowering cholesterol since 75% of people who have heart attacks have normal cholesterol.
Also, CVD mortality is lowered, but other causes of death increase.
We have MVMR studies that look at multiple variables
https://journals.plos.org/plosmedicine/article%3Fid%3D10.137...
https://www.thelancet.com/journals/lanhl/article/PIIS2666-75...
Some MR looking specifically at CRP actually dispute the idea of a causal link altogether
https://www.bmj.com/content/342/bmj.d548
https://www.ahajournals.org/doi/10.1161/01.atv.0000258869.48...
Factorial MR show strong evidence that the risk is additive, in the case of these that look at atherogenic particles and IL-6 signaling
https://www.ahajournals.org/doi/10.1161/JAHA.121.023277
MR looking at specific genes that reduce LDL-C through a variety of mechanisms, including some that lower inflammation, show basically identical reduction of risk per LDL-C lowered.
However, I’m not aware of any evidence showing that higher oxLDL vs higher LDL entails greater risk. IIRC there is a paper that compared oxLDL to ApoB where ApoB was more strongly associated with risk, which doesn’t seem like it would be expected on your hypothesis.
The response to retention hypothesis and the mechanistic evidence supporting it point to oxidation being inevitable once ApoB tagged lipoproteins are trapped in the arterial wall. That being the case, it would be moot whether it entered the wall in an oxidised state or not.
So yes, oxLDL is one of the early stages of atherogenesis, but I’m not aware of any evidence that having LDL pre-oxidised before it’s trapped vs regular LDL increases risk.
I’m always open to new evidence that would change my view, but that’s my understanding of the research landscape at the moment.
> Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All‐cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non‐fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non‐fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non‐fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen.
So the evidence base is a collection of studies where most of the participants had at least one prior indicator of CVD or diabetes, and their outcome is a relatively weak benefit to all-cause mortality, CVD, CHD and stroke. For primary prevention, what you really want is a strong outcome in a study of people without any prior indication of disease [1].
I think the article posted by parent is exaggerating, but even the Cochrane review is pulling its punches here, saying specifically "cost-effective in primary prevention", instead of the stronger claim. Common jokes about putting statins in the water supply aside, there's not a ton of evidence for giving them to, say, otherwise healthy 20-somethings.
[1] Imagine the following, not-uncommon scenario: you have an otherwise healthy patient who is both pre-diabetic, as well as presenting with elevated cholesterol. Statins have a tendency to elevate blood glucose. So which risk do you choose?
The available evidence provides poor guidance.
Lack of data doesn't mean the treatment won't work. There is plenty of reason to think statins work for primary prevention even though it hasn't been proved yet. For most the side effects are acceptable, and the cost is low. Thus for most it is worth trying as primary prevention even if we don't have data to show it works. Remember you are playing with your own life here, and the best evidence we have is on the side of stains for primary prevention - this may change in the future when we get data of course.
In drug development, that is the default presumption, and rightfully so: almost nothing ever works.
> There is plenty of reason to think statins work for primary prevention even though it hasn't been proved yet.
Define "primary prevention" -- do you propose giving this to a healthy 20 year old with no other signs of illness? Younger? Should we "put it in the water", as they say? How about older patients? How old? Or, do you mean someone with symptoms? If so, then what about the case I cited (which is quite common in "primary prevention") where you have multiple things in tension?
The evidence provides no guidance here, and anyone who tells you otherwise is guessing. For what it's worth, though, we agree completely on the need for larger data. I think what drives me most batty about the "appeal to consensus" is that it's almost invariably used as a highbrow-lowbrow way of beating up on people who want to ask the question, which is the first step toward getting the answer!
Extraordinary claims require extraordinary evidence. The cholesterol to heart disease link is one of the best attested in medical science [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15]
And yet when making this very extraordinary claim, the author fails to cite any quantitative data for or against. He does not even attempt to build a qualitative argument by proposing a mechanistic theory of why cholesterol is unlikely to be causative of heart disease. Then he goes on to claim that doctors don't have hard evidence to show that statins reduce the incidence of heart disease, despite the fact that such evidence exists [5]. The post is just 10 paragraphs of fluff that boil down to 'don't trust the medico-industrial complex'
Honestly, I think that blog post is a litmus test on scientific literacy - What convinces you more, data and numbers and charts and tests of statistical significance, or rail-against-the-machine rhetoric and a few scary sounding quotes provided without the associated context?
[1] https://jamanetwork.com/journals/jama/article-abstract/19216...
[2] https://pubmed.ncbi.nlm.nih.gov/25815993/
[3] https://jamanetwork.com/journals/jamacardiology/article-abst...
[4] https://www.ahajournals.org/doi/abs/10.1161/01.CIR.67.4.730
[5] https://jamanetwork.com/journals/jama/fullarticle/2678614
[6] https://pubmed.ncbi.nlm.nih.gov/32507339/
[7] https://www.tandfonline.com/doi/abs/10.1080/07315724.2008.10...
[8] https://pubmed.ncbi.nlm.nih.gov/18061058/
[9] https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.03.384
[10] https://www.nature.com/articles/s41598-021-00020-3
[11] https://www.ahajournals.org/doi/full/10.1161/JAHA.123.030496
[12] https://www.nature.com/articles/s41467-024-46686-x
[13] https://www.sciencedirect.com/science/article/pii/S002191502...
[14] https://link.springer.com/article/10.1186/s12872-021-01971-1
[15] https://www.jstage.jst.go.jp/article/jat/31/3/31_64369/_arti...
The blog is merely pointers to, and excerpts from, other articles on sources such as New York Times and Bloomberg. The blog post can't be bad unless the original sources it cites are bad. Which ones are bad?
The blog post misrepresents some of the sources by exaggerating the certainty of the claims and ignoring any evidence contrary to the point it's making.
It's a bad blog post.
What about this:
Cholesterol lowering is not the reason for the benefit of statins. If it was, lowering cholesterol via any means should have produced the same benefit, but it doesn’t. One obvious way to confirm this is to find therapies that lower cholesterol by different means (i.e., other than statins) and see if they, too, prevent heart attacks. They don’t. See: https://www.nytimes.com/2008/01/27/opinion/27taubes.html (Some will discredit the author Gary Taubes without addressing the points he is raising.)
The main reason why statins work may not be because they lower cholesterol, but because they reduce the inflammation that leads to heart attacks: https://www.bloomberg.com/news/articles/2008-04-15/heart-dis...
This last link aligns with the new findings.
Your comment is an appeal to authority. While I have my problems with characterizing statins as dangerous drugs, the article is not particularly spicy. In particular, this part:
> Because the link between excessive LDL cholesterol and cardiovascular disease has been so widely accepted, the Food and Drug Administration generally has not required drug companies to prove that cholesterol medicines (such as statins) actually reduce heart attacks before approval. So drug companies have not had to track whether episodes like heart attacks are reduced.
...is true, and controversial only amongst people who don't know the evidence. Which, unfortunately, is many doctors and "experts".
In general, saying any variation on "experts disagree" is not a rebuttal to a question of medical evidence. You would perhaps be surprised to know how many practicing physicians have no idea what level of evidence backs the drugs that they prescribe.
I for one appreciated the clarification that it was not mainstream, since sneaking a random controversial take into a comment thread as if it was fact without noting that it's contentious is disingenuous.
No, they don't. If you don't know enough to argue on the merits, don't argue. A count of opinions is not an argument.
> sneaking a random controversial take into a comment thread as if it was fact without noting that it's contentious is disingenuous.
And again, you're justifying your judgment and dismissal based on hearsay. Saying "I refuse to believe it because experts disagree" is fine if you're unable or unwilling to look into an issue yourself, but in that case you have to realize you're basically ignorant.
I realize that we all go through life taking most things on faith, but that also means that you should not cling to the opinions of others as a substitute for thought.
edit: I see you added "I realize that we all go through life taking most things on faith, but that also means that you should not cling to the opinions of others as a substitute for thought."
Don't worry, nobody's doing that here. It's a question of weighting, not clinging. Maybe you mistook "this is not mainstream" to mean "this is definitely false because it's not mainstream"? It does not mean that. It is just helpful context for evaluating credibility.
You're asserting that a extremely well-known logical fallacy is not a fallacy. It's not an HN rule, it's argumentation 101.
The fallacy is where you use an authority in place of evidence. It is not fallacious to refer to consensus or experts.
Else, you end up basically in the "Do your own research"/vaccine denier/climate deniers/flat earth territory. Appeals to experts is not a logical fallacy. It's actually smart, because you get to leverage agreed facts (the earth is round) even though you've never actually been to space to see it for yourself.
The OP literally dismissed the parent based on nothing more than the opinions of others.
> When assessing the probable significance of an agglomeration of empirical data, it’s valuable to know what experts in the field think about the data and their consensus about the inferences we can draw from it—even if the consensus might be mistaken
I already conceded that, if you have no ability or capacity to think or investigate the issue yourself, it's perfectly fine to defer to the opinions of others. But in doing so, you remain ignorant on the matter.
> because the consensus is usually right.
No. I understand that's a comforting belief -- and even politically charged, today -- but it's just an assertion.
> I for one appreciated the clarification that it was not mainstream, since sneaking a random controversial take into a comment thread as if it was fact without noting that it's contentious is disingenuous.
(emphasis mine)
In other words, you didn't just passively ignore the parent (which would be fine), you posted about it, and not only that, you called it a lie. [1].
When you call something a lie like that, you're making an argument, so you'd better be prepared to bring the evidence.
[1] I realize that you're actually saying that it's "disingenous" that they posted this without some kind of disclaimer that it's a "controversial argument", but to the core of the issue: if you need that disclaimer, you aren't qualified to judge the content. For all you know, it isn't controversial at all.
Lacking in candor.
also : giving a false appearance of simple frankness : calculating
You can tell that it's not synonymous with lying because had you said to me "are you saying they're lying?" I would have said 'no'. This is always the case with semantic disagreements: if you want to know if someone intends a certain connotation, you can ask if they would agree with a rephrasing.
The disingenuousness is presenting a non mainstream theory as if it is fact. Anyone reading that initial comment probably has no idea whether "cholesterol and statins are suspect science". Had they said "some people think they're suspect science" there would have been nothing wrong. To claim they're suspect as a fact is disingenuous: it could be true, or it could be that the person posting it is one of those anti-establishment nuts who disagrees with consensus science about everything out of conspiratorial distrust and is constantly smuggling that stance into conversations all over the internet. Since it is very easy to present the state of affairs in a forthright manner, the only reason why someone would present them deceptively is (presumably) something like that. Hence knowing that the view is not mainstream is very useful for evaluating the motives of the original poster.
It's not evidence that they were lying, because that implies intent. No, probably they believe what they wrote. But it's evidence their ability to reason is suspect and possibly corrupted by some ideological motivation and so should be taken less seriously.
Not that I care, really, about any of this. Mostly this kind of antagonism is very frustrating and it's just kinda cathartic to try to shut it down.
My suggestion is that instead of engaging with commenters with your "oo! Logical fallacy! You broke the rules of arguing!" stance you instead try to find some way to productively engage with their actual thoughts. Perhaps figuring out why they said what they said instead of assuming anything you do not understand is a sign of a weak mind that needs to be corrected. You'll find people respond much more warmly to you if you do
There are two distinctly different fallacies of appeal to authority (which overlap, since all of the second are also the first), this form is the form which is a deductive fallacy (appeal to status), but not the form that is a fallacy in inductive argument (which is appeal to false authority). It is important to distinguish them because while deductive fallacies are much more clear cut, they are also far less relevant to most real world debate, which rarely is about proving something is true by logical necessity assuming some set of axioms, but that is the only place that deductive fallacies are inappropriate, since all a deductive fallacy is is a form of argument in which the conclusion does not follow from the premise by logical necessity.
But you have to separate the fallacy from it being supportive evidence of other data.
There is a difference from saying X must be true because Y person said it and they're an expert on Z. But when there is consensus between appropriate experts - such as researchers that specialize in this field - and it is in support of other specific evidence it is supporting evidence that the other specific evidence is compelling.
If I have 10 CPAs explaining a specific bit of the tax code to me and they are pointing out the specifics of the tax code, it is not fallacious to note that these people are experts and are pointing to specific evidence that supports their point.
People are far too willing, today, to defer their thinking blindly to a consensus of opinions, but worse, to accuse anyone who also doesn't defer of being malicious.
There are conflicting incentives here, and as usual we don't care about someone else's p value, we care about argmaxing our own utility functions.
As someone who lost the genetic lottery (has the high cholesterol gene) you bet I care. There is every reason to think that treating cholesterol will increase my lifespan - I'm hoping for quite a few more healthy years.
It’s so obvious it doesn’t need to be stated dude.
> Statins can be beneficial in patients who have already suffered heart attacks. Cholesterol lowering is not the reason for the benefit of statins. If it was, lowering cholesterol via any means should have produced the same benefit, but it doesn’t.
What a blatant lie! Ppcsk9 inhibitors have produced excellent results, even better than statins.
Do you have any?
Vytorin is a combination of cholesterol-lowering drugs, one called Zetia and the other a statin called Zocor. Because the two drugs lower LDL cholesterol by different mechanisms, the makers of Vytorin (Merck and Schering-Plough) assumed that their double-barreled therapy would lower it more than either drug alone, which it did, and so do a better job of slowing the accumulation of fatty plaques in the arteries - which it did not.
See: https://www.nytimes.com/2008/01/27/opinion/27taubes.html
Statins are not evil and they're not a scam, but we definitely need to replace them with something better.
Since 2010, however, the number of statin prescriptions has gone up 75%, and there have been proclamations that not only is the science "settled" because of a meta-analysis laundering past studies (that could never find a convincing benefit to lowered cholesterol), but that 1) twice as many people should be taking statins, and 2) maybe we should just put them in the water!*
What passes for science in medicine is usually bad, but it's exceptionally bad in the cases of the two classes of drugs that are the most prescribed, meant to be taken for the rest of your life, and coincidentally the biggest moneymakers: statins and SSRIs. They both also, even at best, claim very small benefits.
This thread is just going to consist of sloganeering and people calling you ignorant. Or a "denier," in order to compare disbelief in the tiny effect that statins claim (25-35%, under particular conditions) to disbelief in the Holocaust.
* Which was suggested every five years before any of these new, "conclusive" studies appeared. They'll just keep pitching it until they get that payday.
Why would we favour cross sectional data over that produced by more rigorous methodologies?
> the tiny effect that statins claim (25-35%, under particular conditions)
25-35% reduction in one of the west’s leading killers is tiny? Wild.
Regardless, the OP doesn't actually claim that cholesterol is not correlated with heart attack risk. If you read the entire article (not just the headline) it has a section explaining that the results are confounded by the fact that many patients were on statins already and therefore had lower measured LDL cholesterol than they would normally have due to their diet and lifestyle.
LDL isn't the only factor in determining heart disease risk. We've known this for a long time. Measuring LDL in heart attack patients can be misleading because it doesn't represent lifetime LDL area under the curve and they are more likely to be on LDL-lowering therapy than people with lower heart attack risk.
Correct, but if you read the news articles you'll see that they are reporting results from scientific articles and clinical trials. In other words, it is not the reporter's opinions.
Unknown editor
No journal? Committee? Conference?
Ew.
The American College of Cardiology just started recommending that everyone measure hs-CRP, a blood test for inflammation. Why? Because inflammation now predicts cardiovascular events more accurately than cholesterol — especially in people already on statins or those without traditional risk factors.
In some ways, cholesterol has become a victim of its own success. With routine screening and statins, most heart attack patients now have artificially lowered cholesterol. That leaves the remaining risk hidden in non-traditional biomarkers — beyond the usual SMuRFs (standard modifiable risk factors).
I think there's supposed to be some kind of green highlight for comments by the poster but that's missing as well.
Mea culpa.
(There are some people who dispute whether cholesterol is causative, but most cardiologists believe LDL cholesterol, or ApoB, causes heart attacks and strokes --based on both mechanistic evidence and randomized control trials.)
2. Having now read the article, i see that my question was indeed already addressed in the article — sorry for asking silly questions
3. Your good-natured, approachable response is great marketing for your company! I’m not the target audience, but I did click through your marketing material, and probably trust it more because of your response.