Before you assume that LDL isn’t a good biomarker, read the entire article. Specifically this section:
> 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).
There have always been people with high LDL who lived to a very old age and finally died of something other than a heart attack (nobody knows why). Still high LDL after controlling for everything we can think of (cholesterol is cheap to measure so we have a lot of data!) is a strong sign of a future heart attack and so anyone with high LDL should talk to their doctor: there is good reason to think statins will reduce your chance of a heart attack. Which why we measure it and control it.
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)
LDL is a proxy measure that's cheap and easy to measure. It's widely used for screening despite not being perfect, which confused some into thinking it's the one and only thing measure of CVD risk. It's not, though. Many of the tests we look at are proxies and markers, not actually the sole factor for a disease.
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.
My cholesterol is (frankly) through the roof. My GP wanted to start statins immediately. I pushed back and asked what the big deal was -- my RHR is low, BP is normal, my weight is fine, I have an active lifestyle, and my diet is fine. They explained that the cholesterol might build up a blockage in my heart, and that higher levels meant higher increased risk of that. So I asked whether we could just check and see if that's actually happening, and you can! It's a calcium scoring test, and it cost me $150.
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.
You're probably a "lean mass hyper-responders", a phenotype which is actively investigated, initial paper:
Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research
Same story here (though it cost me more - insurance refused to cover it because I did not meet the criteria [0])
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.
Calcium scores only reflect calcified plaque - not soft plaque. CTTA is what you need for that.
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.
LDL is almost always talked about as a singluar thing, even in scientific studies when LDL comes in several flavors.
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.
This doesn't really seem to pan out in reality. Often people with small dense LDL have it as a result of other risk markers. There's a good discussion here - https://www.youtube.com/watch?v=kplh30RmYo8 - the long and short of it is that when you perform mutual adjustment for number of particles, both large and small LDL particles are associated with a fairly similar risk. But if you have the same mass of cholesterol in two individuals (LDL-c) and one has SD LDL and the other has LB LDL, the latter has fewer LDL particles and therefore lower risk, so it can appear that LB LDL are less risky if you're only measuring cholesterol mass.
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.
The Jupiter trial clearly stated that those with low hs-crp didn’t benefit from LDL-C reduction, only those with high hs-crp had reduced CVD events due to LDL-C reduction.
PCSK9 inhibitor trials have shown significant benefit for reduction in CVD events independent of whether or not the inhibitors lowered hsCRP. Ezetimibe makes an impact on events without reducing hsCRP when administered on it's own. (But it is generally administered with a statin, and it seems that the combination does result in lower hsCRP than a statin on it's own)
The claim I was addressing was that we don’t have evidence of statin efficacy for primary prevention. My point was that JUPITER seems to be evidence this isn’t the case.
> Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.
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.
> If you have normal cholesterol though - we have long known that people with normal cholesterol also have heart attacks.
Just to continue on this line, we also know that people with a genetic disposition for low cholesterol have a significantly lower risk of coronary heart disease than people with ostensibly normal cholesterol levels. It is one of the most proven, obvious correlations (more cholesterol increases the incident of CHD) in medicine.
Some snake-oil merchants, usually pitching a book or supplement, have often tried to muddy the waters by pointing out that someone at death's door often has very low cholesterol (they usually aren't eating, and cancer often "eats" cholesterol and leads to low levels), trying to then extrapolate this out.
These people with genetically low cholesterol, however, have other issues. Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. Many individuals with FHBL develop an abnormal buildup of fats in the livercalled hepatic steatosis or fatty liver.
You have to understand the point which you’re not yet able to put in your head. Yes it is true that lowering cholesterol lowers cardiovascular disease. No one here is disagreeing with that. What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease. I don’t know why this is so hard to understand. Lowering inflammation not only would reduce cardiovascular disease, but also cancer, arthritis and a multitude of other diseases.
> What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease.
interesting idea which I have heard before. However so far as I can tell we don't know if it is true. It seems to fit the evidence that the two are independantly causes of heart attack, when combined it is worse.
maybe someday science will figure this out but it is not easy and so will take a while. Until we do I avoid saying things with high confidence.
Cholesterol is more of a proxy "smoke" or "firefighter" measure than a measurement of the actual fire. It's very much a wet streets cause rain kind of thing.
Artificially eliminating the firefighters doesn't necessarily mean you've solved most of the problem.
Heart disease is a far more complicated problem than "cholesterol" or "cholesterol + inflammation", but humans and patients mentally gravitate to silver bullet thinking, which makes it really hard to work with. One interesting measure I've encountered is the lipid clearance rate, but it costs something like +$20k to measure and is not something a doctor can order from a lab; it's typically only performed in research settings.
This isn't necessarily true. High content of certain cholesterols in the blood does cause heart attacks. It doesn't just indicate it - it actually causes it.
And, we have shown the mechanism of action. Certain cholesterols will build up on artery walls, constraining the flow of blood. When there is too much build up and/or the vessel is too narrow, blood can be constrained too much, causing loss of blood flow and therefore oxygenation. The heart has MANY capillaries and requires a lot of oxygen.
Comments like these just aren't based in reality. LDL levels are not a proxy or a wet streets cause rain. We even have a strong understanding of the mechanisms in which cholesterol causes things like heart attacks, strokes, peripheral arterial disease, etc. etc. etc. Something has to deposit plaque in your arteries.
Yes, from a mechanistic standpoint, inflammation is also an important causal factor. Lp(a) is also an important factor for people that are genetically predisposed to high levels - it also deposits plaque, and is one of the reasons ApoB is recommended. Most people don't have worrisome Lp(a) levels but enough do that we've been missing them, and we now also have good treatments for them - PCKS9 inhibitors reduce it by ~1/3rd, and we have Lp(a) specific medications in phase 3 trials that are even stronger.
But we know that statins work. This is some of the most established science in health. I keep seeing claims in these comments from people stating otherwise, but it just doesn't match reality.
We also know that lowering LDL in and of itself lowers inflammation within the arterial wall, though this isn't necessarily reflected in hsCRP. We know that foam cell activation and cytokine signaling increase inflammation at the site of the plaque, which results in further deposition, and these require ApoB particles be depositing plaque there to begin with. Some PCSK9 inhibitors show zero change in hsCRP results yet still show less localized inflammation - due to the significant reduction in LDL-C and Lp(a) particles.
Lowering inflammation also works for reducing events independent of lowering ApoB particles - colchicine works even though it does nothing there - but if we're really trying to stretch the fire analogy, it's more like LDL and Lp(a) are the years of unmaintained brush and flammable debris in a forest, and inflammation is the strong winds. Both can lead to the spread of fire even without the other, fire can still spread even in the absence of both, but having either and especially having both will greatly increase the risk of the fire continuing to spread.
>These people with genetically low cholesterol, however, have other issues
Neat.
>You have to understand the point which you’re not yet able to put in your head
Nowhere did I ever dismiss other causative inputs. All I did was reply to some probably-listen-to-chiropractor people who sure are trying incredibly hard to downplay cholesterol.
If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
Why don’t you stop your appeal to authority arguments and focus on the facts.
It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
If that is not interesting to you then you have an odd bias. I merely saying that inflammation is the risk factor that matters more than high cholesterol. You can lower cholesterol for someone who has high inflammation and reduce heart disease, but reducing inflammation is more important overall.
>If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
This is such a silly statement I'm not sure where to begin. Plenty of people smoke and drink and don't die of issues related to smoking or drinking, but smoking and drinking are bad for you.
Individual response to things varies. No one reasonable is going to say that because such and such person did X, Y, Z things that we know are bad and didn't have a negative outcome that we must flip the script on if those things are bad are not. Exceptions exist for a wide variety of reasons.
> It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
Calcium score does not tell you how much plaque you have in your arteries - it tells you how much calcified plaque you have in your arteries. This is NOT the same thing. You need a CCTA to tell if you have soft plaque or not.
I'm sorry, but you're just severely misinformed here and spreading all sorts of dangerous misinformation all over the comments here.
You’re comparing cancer to LDL. So you’re literally saying LDL is like cancer in the body. That’s ridiculous. The body does not need cancer, but it does need LDL to transport fats around the body.
And for your grandfather, yes, smoking does not cause cancer, smoking increases the risk of cancer, and cardiovascular disease, but there are other factors that play into that including nutrition and genetics.
Do you understand the distinction between increasing risk and causing?
This is the problem with western medicine, the constant search for a single cause disease because It’s not so complex that a non-holistic person can understand it.
If I was a legitimate scientist, I would look at your grandfather‘s case in curiosity and amazement. What was it that he did that proved him immune to the ravages of smoking? Do you know there were some people that had HIV that did not end up with AIDS? And the good scientist use those anecdotes to find a cure for AIDS and the current treatments that are now making people live long lifetimes with HIV.
> The body does not need cancer, but it does need LDL to transport fats around the body.
Of course the body needs cancer.
Cancer is your own bodies cells. They're essential for you being alive. And, cells with damaged DNA train and hone your immune system.
You have millions of cancer cells in your body right now. Your immune system is killing them as we speak.
If a few happen to slip through, then that's we would say you have cancer. Why might they slip through? Your immune system makes mistakes. Because everything makes mistakes.
> What was it that he did that proved him immune to the ravages of smoking?
Um, nothing?
Is this your first day on Earth? Life is not an algorithm.
Everything is risk, everything is probability. Smoking increases your risk. It doesn't give you anything.
Your HIV and AIDS argument is just fucking stupid. Sorry to be blunt.
Yes, SOME things are A -> B. That is an extremely rare exception to the rule. Extremely. That almost never happens.
Like, if I drive fast, I might die. Might. Its not a garuantee.
I can drive 150 every day and live, or drive 10 and die immediately. That's life. Welcome to risk and probability. That's just how things work.
Having LDL and no heart disease doesn't prove anything to anyone. That doesn't prove LDL doesn't cause heart disease.
LDL levels is too complex to be used as the litmus test it has become.
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:
> 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.
(OP here) LDL is still a good biomarker, but ApoB is a better biomarker for the same undelrying risk factor -- each atherogenic particle (LDL, VLDL, IDL) has exactly one ApoB molecule.
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.
Their comprehensive men’s panel is $200, which seems like the most comparable package. (The list of biomarkers above is a subset of the ones in our panel—obviously if you remove biomarkers, you’ll end up with a cheaper price.)
Unrelated to the topic, but does anyone know if an equivalent service (à-la-carte blood testing with online booking) is available in Europe, specifically the Netherlands (or France) ?
Anecdotal advantage that I've heard of but not verified.
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.
True - they wouldn't unless it is discovered and disclosure is mandated by a legal process. otoh - OP could provide a service where these results are completely anonymized if the person requesting the test so desires.
FYI the above poster is the founder of the company selling these tests (EDIT: He edited his comment to include the "OP here" intro after I posted my comment. Thanks!)
> 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 updated the above post to say (OP here). I thought it was fairly clear from my phrasing of "we offer the tests as cash pay", but never hurts to be even more explicit.
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 $190 panel. We've actually dealt with this exact situation in the last month, since every so often labs will make a mistake when they process the order (we obviously fix these situations). Perhaps the insurance companies aren't sane (a topic for another day), but this is unfortunately how the system works today.
Commenting to add - Insurance negotiated rate may actually be 1500$. If it is and they charge insurance 1500$. They legally cannot charge an individual a different or lower rate. Even if that person doesn’t have insurance and offers to pay cash.
This is one of those weird horrible traps health insurance puts you into. OP may charge insurance 1500$, 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.
The problem I'm seeing here in Norway is that the bar to put people on statins is way too low given the severe side-effects and likely consequences of long-term statin use, even low doses.
I think LDL is a good biomarker, just not in isolation, and especially not a "one-size fits all" metric for individual humans.
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.
This just isn't true. Modern statins have extremely good efficacy to side effect ratios.
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.
We have all sorts of RCTs, blinded studies, placebo controlled studies, MR studies that look at genetics, meta-analysis, etc. etc. etc. that all support the causal link of cholesterol... I've linked literally dozens of these in the comments for this article. If you care, feel free to look at my recent comment history - it's all in there and all my claims sourced.
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.
LDL and BMI's u and j shaped curves on all cause mortality disappear when you start controlling for other factors like a variety of diseases. Cancer, kidney disease, AIDS, etc. Lots of people end up with very poor nutrition when close to death from these diseases and end up with low bf%/bmi and LDL levels.
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.
> 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.
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:
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:
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:
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.
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.
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.
> 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.
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.
My favorite definition of heart disease is "when circulating fats in the blood (lipids) are pushed by a driving force (blood pressure) into a vessel wall that is vulnerable (endothelial dysfunction)." IMO this gives a good mental picture of how all of these risk factors fit together.
But if they have lower cholesterol and still have a heart attack, then certainly the causal link is not quite there. It seems you’re suggesting it’s a good proxy measurement if untampered by statins though
I personally have naturally very low cholesterol and also had a heart attack in my 30s. There are a handful of case studies published of other people in this scenario but it is a rare enough scenario, and it is vanishingly rare to have years of reliable cholesterol results without known high risk.
I'm not sure I follow - is this what you're saying:
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.
Correlation is informative, but neither necessary nor sufficient for causation.
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.
We could grant all that for the sake of argument but it wouldn’t interact with anything I said.
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.
Statins are generally administered after decades of exposure to high cholesterol/ApoB.
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.
In medicine, “mediates” is mostly synonymous with “facilitates”. So ‘lifelong exposure to cholesterol facilitates atherosclerosis’ - mediates is a bit softer since health changes often involve multiple pathways and can be impacted by many other processes.
There is a detailed lipid panel (Lipofraction NMR) as along with the HDL/LDL/TriG estimates they get today. There is a lot more detail in there. Statins help reduce LDL but the detailed lipid panel may still show a very high level of LDL-P and Small LDL-P which still increase risk.
If you're going for more testing, I would definitely suggest the lipofraction.
The most recent evidence is that if you’re measuring ApoB and Lp(a), you’re capturing the same information as fractionation (with the bonus that the former two are slightly faster and cheaper at most commercial labs):
LDL has always been both a worthwhile measure and target. It's not perfect as a measure - it doesn't account for Lp(a), for example, and why ApoB is a better indicator for the atherogenic particles portion of the equation - but we know that lowering LDL lowers the risks of ASCVD and results in better health outcomes. I've linked quite a few studies over the comments here backing this up with huge quantities of data points.
Yes, LDL is the best we have since they won’t bother to measure oxidative stress nor inflammation in the human body.
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.
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.
> But lowering your LDL does not prevent heart disease. There are many many people with normal LDL who have heart attacks.
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.
Lowering LDL isn't equivalent to a seatbelt. A seatbelt is a safety device that performs a function in an accident.
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.
>Lowering LDL doesn't actually do anything on its own
Is this some sort of weird philosophical statement? Because, of course, it's completely nonsensical, and completely at odds with all data on this file.
Lowering LDL reduces CVD incident rates, with no other interventions. People with genetically low LDL also have lower CVD incident rates. This is extraordinarily well proven.
So it sure seems -- you know, 100% of medical science -- that lowering LDL does "something".
The human body is a complex machine, however, and CVD is multifactorial, and for CVD to develop the current thinking is that you need inflammation and high cholesterol over decades. Inflammation can be caused by things like high blood pressure and the like. But everyone has inflammation to some degree as a facet of living, and the easiest component of that to treat (not just measure) is LDL.
And yes, there is an industry of cholesterol denialists, among whom there are just loads and loads of chiropractors. These clowns have built armies of poorly informed disciples that run to HN to tell us that cholesterol doesn't matter and lowering LDL doesn't do anything.
> People with genetically low LDL also have lower CVD incident rates. This is extraordinarily well proven….. you need inflammation and high cholesterol over decades.
We know that low LDL does not prevent CVD. Therefore we know that you do not need high cholesterol over decades.
He said LDL does not do anything on its own, meaning that there’s another factor that causes oxidized LDL, which triggers plaque formation and heart disease. As I pointed out in another post over 75% of people who have heart attacks have normal LDL.
I get my CRP measured every year. I have zero inflammation and I am in my late 50s. So not everyone has inflammation.
You’re saying a lot of nonsensical stuff in your comment like high blood pressure causes inflammation , which tells me you are not serious in this discussion. Because that makes absolutely no sense.
Localized foam cell activation and cytokine signaling does not necessarily raise hsCRP yet allows for continue plaque deposition. This is a very well understood mechanism.
No one knowledgeable here is saying that inflammation isn't worth paying attention to, but people acting like because inflammation is also important that LDL does nothing just aren't living in reality.
Your comment about blood pressure actually reveals more about your knowledge here than the person you're replying to.
FDG-PET is a signal we can use to detect tissue inflammation, and we know that higher blood pressure is highly correlated with increased FDG-PET in arterial walls:
Blood pressure results in shear stress to your arteries. This results in several things that amplify Angiotensin II and NF-kB activity, including expoosing adhesion molecules which then results in foam cell activation and cytokine signaling, etc.
It is quite well established that high blood pressure will contribute to increased inflammation.
It's like saying a flying bullet can't do anything on its own. It is a meaningless statement.
>As I pointed out in another post over 75% of people who have heart attacks have normal LDL.
The actual study authors were advocating for lower LDL guidelines, particularly among the elderly.
A heart attack is the destination, not the journey. What someone's LDL was at admission for a heart attack says literally nothing about their state for the decades before. In actual studies tracking cholesterol, even over a five year period lowering LDL has a potent beneficial effect.
>You’re saying a lot of nonsensical stuff in your comment like high blood pressure causes inflammation , which tells me you are not serious in this discussion
Hypertension can cause endothelial inflammation, leading to blood vessel damage and promoting the release of inflammatory mediators. This is extremely well documented, and it's why getting hypertension under control medically is considered extremely important in the CVD battle. Inflammation and hypertension often are found hand in hand, and there is uncertainty over the cause and the effect, but strangely controlling hypertension alone dramatically reduces inflammation. Weird, right?
>I have zero inflammation
Sorry, but LOL. Not only is that a singular and very narrow test, inflammation is literally just a facet of living. As is oxidization. There isn't a single human alive with "zero inflammation", nor is there anyone that has magically non-odidizing LDL.
If you don’t understand the difference between acute and chronic inflammation, there is no longer any reason to continue this conversation with you. Yes, I apologize because I didn’t specify the difference, but I thought you would be intelligent enough to know the distinction.
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.
>But lowering your LDL does not prevent heart disease
Literally one of the most proven truths in medical science is that LDL levels has an almost directly relationship with CVD risk over the long term. Someone with low cholesterol can of course still have CVD, but their odds are much better than someone with high cholesterol. And of course the damage from cholesterol is additive, so the earlier you control LDL, the more of a benefit.
>A new national study has shown that nearly 75 percent of patients hospitalized for a heart attack had cholesterol levels that would indicate they were not at high risk for a cardiovascular event, based on current national cholesterol guidelines.
The damage from high cholesterol happens over decades. Yet the people who actually have heart attacks are often older.
So yes, if gramps spent his life with high cholesterol but now he barely eats and is sedentary, he might have low cholesterol now but that says literally nothing to what you're claiming it does.
Yes, much like wet streets are a high predictor of rain. Or smoke, firefighters and wood are a high predictor of fire. The firefighters are not causing the fire, neither do the wet streets cause rain. This is what people are trying to tell you. If you remove the firefighters only, then you might make it worse. If you do something to cause the firefighters to go away, probably because there isn't a fire anymore, then you did the right thing. The important thing is not to goodhart's law yourself into doing the wrong thing.
This would be a fair analogy if we didn't have studies with a temporal component, but we do. We look at individuals before they get disease then track them over time to see what predicts disease. So we can see, per your analogy, that the fire is there, then the firefighters turn up.
No. They’re saying that damage is cumulative over a lifetime - plaque deposition - so that a point in time snapshot of LDL says little about lifetime exposure. If I live my life with high LDL and only get on statins at 65 I might have low LDL when I have a heart attack but the damage came from the decades of high LDL.
The current guidance from the AHA and NLA is that lower is better for as long as possible.
Lower cholesterol helps but lowering inflammation helps everyone. As I’ve said in another comment over 75% of people who have heart attacks have normal LDL levels.
And lower cholesterol is not without its own risks. You need cholesterol to make hormones and things like CoQ10, which are important for our health. So what’s better? Lowering oxidative stress and inflammation or lowering cholesterol?
LDL levels at admittance do not tell us what their lifetime LDL levels were. But even your own link is arguing for lowering the the number at which we consider LDL levels risky.
PCSK9 inhibitors when coupled with statin therapy have gotten people to ~10 LDL without negative impact in clinical trials. The body is good at producing cholesterol where it needs it - it doesn't pass the blood brain barrier, yet the brain is full of it. It produces it's own, the same as quite a lot of other tissue
For hormones, de novo synthesis of cholesterol is a thing when it comes to steroidgenesis, as well as recycling and re-uptake. PCSK9 inhibitor studies specifically looked at this because of this concern, and found cortisol/aldosterone/testosterone/estrogen/etc. were not impacted by having very lower levels of LDL-C.
The issue with statins and CoQ10 isn't cholesterol - it's the mevalonate pathway. They block a reductase in the pathway and this results in lower serum CoQ10 levels. Data around if this is of any clinical relevance is a mixed bag, but this is easily supplementable if needed, and should not be a reason to not take life saving medication. PCSK9 inhibitors make large dents in LDL but do not impact CoQ10 levels at all because they do not impact the mevalonate pathway.
There is a theory that cholesterol elevates in response to circulating endotoxin (dead bacteria cell walls).
Lipoproteins can bind to the endotoxin, and clear it or at least stop immune cells from reacting to it.
This response increases LDL, but decreases the immune activity that would otherwise be created by letting the endotoxin circulate.
So LDL is a defense mechanism against the body's own response to circulating endotoxin as well as the endotoxin itself.
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.
Why would a significant part of the population have dead bacteria circulating throughout their bloodstream? Bacteria live and die in the gut regularly, so it seems exceptional that parts of it would enter circulation and somehow avoid metabolism.
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.
Bacteria entering bloodstream is quite common it seems, gut is not perfectly sealed and less sealed because of bad lifestyle choices. I think the article points out that treating cholesterol doesn’t treat the root cause and possibly! ineffective in itself to lower heart disease risk as something else is causing direct health threatening problems.
This is all just a hypothesis, and a very new one. We know almost definitively that high cholesterol causes heart disease and lowering cholesterol lowers your risk of a heart attack.
Alcohol, NSAIDs, stress, obesity, or chronic inflammation
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.
Saw this the other day which may tie in with what you're saying? "Bacteria present in carotid arterial plaques are found as biofilm deposits which may contribute to enhanced risk of plaque rupture" : https://pubmed.ncbi.nlm.nih.gov/24917599/
That does seem related, but it suggests something even more unexpected, which is that live bacteria are forming biofilms in arterial plaque.
So the LDL is picking up live and dead bacteria and then adhering to the side of arteries.
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).
I certainly get the skepticism. You might find the JACC article (which is an American College of Cardiology consensus statement) interesting, since the ACC is a neutral party here (and reviewed all the evidence around hs-CRP).
Yes, and the internet has helped quite a bit with this.
Instead of a small group of people having access to research through university or hospital publishing networks, everything circulates on the internet for anyone to look at.
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.
hs-CRP is well known as a useful biomarker and it is cheap to test too. If you look at page 13 of the GrimAge 2 paper, you'll see CRP is one of the factors most negatively correlated with their aging clock, in fact basically as strong of a negative impact as smoking. https://escholarship.org/content/qt6k46n006/qt6k46n006.pdf
This new news is about research published in the Journal of the American College of Cardiology.
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.
>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.
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.
Just thinking out loud here, but I wonder if the immune activity is not the problem, but some kind of destructive process that is triggering the immune response. A continuous onslaught of destruction tends to make things break down faster.
The C reactive protein itself doesn't cause symptoms on its own. It's produced by the liver in response to signals from immune cells.
It actually binds to bacteria in circulation, so if anything it helps.
As a data point, it can vary by >1000x during the course of a disease, and won't be something that people feel or complain about separate from the other symptoms.
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.
Chronic inflammation (a general systemic thing) is the thing we're mostly concerned about for heart health. The hs-CRP metric itself will pick up both acute inflammation (if you get sick) and chronic inflammation.
I have always read it as systemic. Which is why low carb diets seem to do wonders for a lot of people's cardiovascular systems, somewhat paradoxically. If you go really low carb (<20g / day), the first week or two you can lose a ton of weight, but much of it is water, which detractors point to as "well, you're not losing fat!" But, imagine what this does for inflammation. That is 7 pounds of fluid you are no longer carrying and pumping against. It's basically a gallon. The first round of keto I did, I lost a ton of weight the first month (~20 lbs), and my blood pressure plummeted to the point where I was dizzy all the time, and I had to supplement with salt and magnesium. I remember a study I read probably 15 years ago where they looked at cross-sections of arteries before and after starting a ketogenic diet, and there was significant reduction in inflammation after just a few weeks, IIRC. I just tried finding it on pubmed, but can't find the right incantation of search terms to dredge it up. There are countless studies like this.
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.
"But, imagine what this does for inflammation. That is 7 pounds of fluid you are no longer carrying and pumping against. It's basically a gallon. The first round of keto I did, I lost a ton of weight the first month (~20 lbs), and my blood pressure plummeted to the point where I was dizzy all the time, and I had to supplement with salt and magnesium."
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.
“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]
What exactly does your diet consist in? What other adjustments have you made, e.g. in sleep or exercise?
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.
> 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.
Yes, you are correct. Nothing wrong with walking, helps keep weight low and fat cells are a huge source of oxidative stress. Better to eat low calorie, high nutrient dense foods.
I have genetically high cholesterol. But otherwise I exercise quite a lot and healthy. I’ve been told not to worry about cholesterol unless other indicators start to climb. So I just generally avoid high saturated fat foods (sat fat in food matters more to blood cholesterol than food cholesterol).
Have you measured your Lp(a)? It's the strongest hereditary risk factor for heart disease. (Each Lp(a) particle is essentially a "normal" cholesterol particle with an extra protein that makes it 6x more atherogenic.)
How old are you? I'm not a doctor, but my impression is treatment for cholesterol is not considered worth it until you are "older". Depending on how high, older can range from 35 to 50. (actually a better marker is probably when did your grandparents have heart attack, start treating somewhat before then). Which is to say get regular checkups because you will likely be put on treatment in the future, but not today.
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.
The guidance has been changing significantly over the past few years. The consensus from expert organizations is now that we should be lowering it far earlier.
To the point of the original article, the consensus is probably doing people more harm than good. My mother had a heart attack at 45. My brother died of a heart attack at 48 and my other brother had a heart attack at 47. My cholesterol has been over 200 for at least 15 years and I’m in my late 50s. My calcium artery scan was zero and all heart sonograms are perfect.
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.
Anecdotal data does not disprove the millions of data points from well controlled well structured RCTs that have been poured over by the brightest minds in the field.
The positive impact of lowering LDL is some of the strongest science we have on health.
You mean the positive impact of consuming statins. Consuming statins coincides with lower LDL so I can imagine people conflating the two variables. I'm sure taking statins also has other effects on the body.
No, I mean the positive impact of lowering LDL. Statins of course show positive impact, and yes, including from also lowering inflammation. But so do other drugs that lower LDL through other mechanisms, including ezetimibe, bempedoic acid, and pcsk9 inhibitors. MR studies on genetics also show that lower LDL even without other factors that reduce inflammation significantly reduces the risk of of negative ASCVD outcomes.
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 dismissal of anecdotal data is why science has been stalled and people are still sick.
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?
High LDL or Lp(a) on its own causes enough localized inflammation to continue plaque deposition. We can’t drive down every cause on inflammation to 0 to the point that there is zero plaque deposition at all in the presence of high LDL, there are just too many causes. Even temporary increases in inflammation from natural processes can deposit plaque is you have high amounts of atherogenic particles. And once they deposit, they begin to cause inflammation independently. Not all inflammation can be measured by hsCRP.
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.
Heart disease progresses over decades and there's no solid evidence it can be reversed. You don't want to wait til you're 18 months out from a heart attack to do anything. I don't think this is good advice
> Heart disease progresses over decades <...> You don't want to wait til you're 18 months out from a heart attack to do anything. I don't think this is good advice
Correct. The idea is commonly referred to as "LDL-C Burden"
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.
Eating excessive saturated fat is what your liver turns into too much "bad cholesterol" and what you need to watch if you're having cholesterol problems. Cholesterol in food doesn't usually translate to you having more cholesterol in your blood.
I would have to go dig up the source for this, but I believe that genetics play a role on how your body handles dietary cholestrol. For many it's not a problem, but for some it is.
Yeah, it's that and the relationship between dietary cholesterol and serum cholesterol isn't linear - once you're consuming a certain amount of dietary cholesterol, adding more doesn't make much difference to serum cholesterol.
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.
This is the study that finally confirms what a lot of people in the health/bio-hacking space have suspected for years! It’s not that cholesterol is irrelevant—it's still a primary risk factor—but it's clear it's only half the story.
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.
Note that the $190 panel includes not just hs-CRP ($59), 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.
Anyone know how weight lifting might be related to this?
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.
I dont know the direct answer to your question, and am not a Doctor nor researcher... but using a generally applicable health pattern -- it's important not to equate acute anything with chronic anything. Eg: Acute fat loss via exercising while fasting does not seem to relate to body composition changes over 12 weeks. Similarly the self protective process of hormesis seems to actually create greater health - like reactions to heat from sauna usages for example.
Fundamentally weight lifting should reduce inflammation, but at the same time I’m less certain about how things like protein powders or very high protein intake factor into this.
Weightlifting increases inflammation acutely, not chronically. But if you work out too much without enough rest, then the inflammation is chronic and that’s where the danger is. Over the long-term resistance training decreases CRP level levels when adequate rest is involved.
I'd guess this is persistent, systemic inflammation. So I, as someone with IBD, have higher levels of CRP, so am probably a prime candidate for this kind of early death (despite having quite good cholesterol)
is there something akin to a continuous glucose monitor but for inflammatory biomarkers? it would be so dope to be able to watch your body respond in real time to the foods you eat the way you can with a cgm
It specifically measures carotenoids through the optical heart rate sensor -- you mostly get carotenoids from eating vegetables, and they do reduce inflammation.
It always did... even the way cholesterol recommendations have been aren't really good in and of themselves. The better marker is Triglyceride to HDL ratio, in terms of correlation to morbidity. Not total, not LDL by itself without quality tests.
Trig/HDL and LDL/HDL ratios are outdated science that have been superseded by our better understanding of the causative factors and our ability to drive LDL way lower than we could in the past.
MR studies have shown very little evidence higher HDL does much, if anything, to prevent CVD or serious adverse events.
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.
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.
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
Good luck to you, hope you keep on top of it. Do you know if you have high lp(a) out o curiosity? Curious what drives these events in cases such as yours.
> Curious what drives these events in cases such as yours.
In my case, I got dealt a very, very poor set of cardiac genes. Everyone on my mother's side has had at least one heart attack, though they generally started around age 50.
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.
I walk my kids to school every morning. And I walk to pick them up. It's a 10 minute walk to get them, so that's about 40 minutes of walking each day. I could drive and get there in 2 minutes then wait in a line. It would probably cut the time in half, but walking is better for the environment (noise, pollution, safety, wear and tear), me, and my relationship with the kids (we, y'know, talk while we walk).
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.
That's great - for me the problem is weather. Where I live it's hot, >80s Fahrenheit, >28 celsius, for 4 months a year. So unless I want to always be sweaty, I can't really walk more then 10 minutes at a time.
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).
In the US a large number of people have moved to suburbs in the south. On a bad year our lows are in the 90F range. Add in asphalt architecture and in the sun temps are commonly 125F+
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 someone goes from not exercising at all to walking 30 minutes a day, it will make a definite dent in blood pressure. Changing diet will add another dent. Walking for 90 minutes a day will make a bigger dent than 30. The degree of the changes reflects the degree of the results.
Why would they be platonists? Diogenes was the Greek philosopher who shunned material things and famously lived in a barrel. Seems like that would be the ancient Grecian philosopher that might inspire some form of voluntary homelessness.
There's a (apparently un-substantiated[0]) claim that Plato was buff; "Plato" was apparently a nickname and meant "broad" in Classical Greek, referring to his wrestlers physique.
[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.
Ah fair, I meant in that they're homeless so they must live in their heads/in ideas which are more real to them (hence Plato), so they're shredded from always being active and outside.
Avoid allergenic foods, Highly processed foods. Get plenty of sleep. Manage stress. Avoid toxins like alcohol or smoking. Avoid chemical irritants including perfumes, dyes, fragrances in detergent or soap, ….
Not sure why this is downvoted, this is correct on all points. I've been on a journey to lower chronic inflammation and you would not believe how hard it is to find stuff that doesn't have "fragrance" or other mysterious potentially-inflammation-causing substances.
> 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.
Honestly that used to be a common midday break for me at work.
2 slices of bread per sandwich with ham and/or cheese inbetween the 2
I never gained weight and always ate a lot tho and as i got older i've become more active.
I saw an interesting video that mentioned a study.
Even though 10K steps a day is considered an arbitrary amount, this study found that level of activity counteracted inflammation.
>And avoiding putting stuff in your body that makes your immune system react like air pollution, microplastics,
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.
Yes, there is that risk. On the other hand there is the risk of stroke, which I am more scared of, which is why I take aspirin. What is the impact of NSAID Gastritis? How bad is it and can you recover from it?
If you have been prescribed the Aspirin then it’s important to continue or discuss with your Physician. But as I mentioned in another comment, there are gastro protective Aspirin pills available.
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).
I was taking a lot of Ibuprofen due to frequent illnesses while simultaneously needing to be healthy. I started to get terrible heartburn that caused me to hunch over at times. Tried dietary changes. Finally, I happened to read that this and ulcers is a side effect of NSAIDs. Switched to acetaminophen, and was generally more judicious about taking fever meds, and I haven’t had heartburn in months now.
The conventional wisdom is that low dose aspirin prevents heart attacks by lowering the tendency for blood to clot. I've long had a theory that it was the anti-inflammatory effect that had the greatest benefit.
Potentially inhibiting IL-6 or reducing Lp(a). We'll get an early glimpse from some robust Phase 3's next year. These have been in the works for several years with tens of thousands of patients enrolled - it'll be an exciting set of readouts.
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.
I have never understood how one supposed to reduce stress. For me, stress is a signal that there is some threat in my environment. Such threats are often outside of my control. How is one supposed to reduce something that he or she has little control over?
Well, not with that attitude. Surely you've seen people on life that you felt overly stressed themselves. It's not just a natural bodily reaction, how you react to the reaction. Some people can spiral out of control with stress, amplifying it. Other people can relax and not let it get to them.
Try meditation? Not the religious stuff, just breathing exercises and trying to clear your mind
> Some people can spiral out of control with stress, amplifying it. Other people can relax and not let it get to them.
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?
I'm not a doctor, but I am passionate about this stuff in my own life.
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.
I am extremely skeptical about the need for this kind of shotgun "health marker" blood panel test. Even granting the premise that whatever ML algorithm they use to interpret the results is at all accurate, the upshot is unlikely to change the general recommendations regarding heart disease anyway (control blood pressure, stop smoking, manage diabetes or pre-diabetes, maintain a healthy diet and meet the physical activity guidelines).
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.
Thank you to the reply; the fact that there is a qualified human in the loop to review test results is very encouraging. I stand corrected on my initial assessment.
Curious about infliximab being unhelpful or even harmful for cardiovascular risk; I'm not sure if there were any confounding factors re. people on infliximab not generally being in great health to begin with. But back when I was on infliximab I had some not-awesome systemic side effects, so I wouldn't be chocked if it's just not great for your cardiovascular health in general. (And that's still probably a worthwhile tradeoff if you're the kind of person who's being prescribed infliximab.)
If you don't mind me asking, what was your like on Remicade (and/or what you swapped to)? I suppose I have the option of taking a biologic (not Remicade) for an immune mediated condition, but I can't help but shake the feeling that the cure might be worse than the disease in my particular situation.
I don't mind at all! I started on Humira, switched to Remicade, now on Skyrizi. Remicade worked better than Humira for me, but it's a much stronger drug (and I worked my way up to a higher-than-default dose), so I was prone to some weird skin infections that I hadn't had on Humira despite both drugs acting on the same mechanism, and my immune system was weaker overall. Nothing serious, just annoying. And I wasn't actually responding that well to Remicade overall.
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.
That all makes sense! If your skin stuff is relatively mild and isn't causing you too much trouble, a topical approach seems warranted (and is certainly a lot cheaper). That said, if it ever does get worse to the point where you're in genuine distress, keep in mind that the psoriasis-only dose of a drug like Skyrizi is a lot lower than the big fat dose I take for Crohn's disease, and less frequent as well. Also keep in mind--and hopefully it doesn't come to this--that psoriasis is highly comorbid with both Crohn's/colitis and arthritis, so if you start to experience worsening digestive issues or joint pain, definitely get those checked out. The silver lining is that if you do experience comorbidities like that, finding the right treatment (usually but not always a biologic) can knock them all out at once.
(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!)
I am an Empirical Health customer, and the app has numerous bugs. Please, fix them before blogging! Thank you for your attention to this matter. MAKE APPS GREAT AGAIN!
Thank you! Just emailed you with the debug code. By the way, on the debug code screen, it says that my push notifications are off, but I was never asked to enable them within the app itself.
This isn't surprising, and its refreshing to see more research that questions the cholesterol hypothesis finally gaining some traction.
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.
This doesn't question the cholesterol hypothesis. The link between higher ApoB and increased risk of CVD and death is one of (if not the) best understood and well researched exposure/outcome relationships in human health research.
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?
This paper isn't directly challenging the cholesterol hypothesis but it is a step in that direction. 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.
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.
I didn't say there can't be multiple causal factors, and in anything related to biology I would expect there to be multiple factors.
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.
The cholesterol hypothesis certainly leaves room on the table for multiple causal factors, and from very early on we knew that inflammation was key to plaque actually being deposited on arterial walls. The cholesterol hypothesis has always been that serum cholesterol are linked and that decreasing serum cholesterol significantly reduces heart disease. It is not that serum cholesterol is the sole source of heart disease.
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.)
Why would that raise questions about whether cholesterol levels are correlative rather than causal?
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.
That isn't the a good comparison. You are describing two pathogens that can both be found to be highly correlated to risk of lung cancer in isolation. A smoker with no known asbestos exposure is still more likely to get lung cancer than a nonsmoker, and visa versa.
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.
What I’m arguing against is the form of the argument you’re making when you say:
> 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?
Interesting that official recommendations are catching up to what some clinicians on the edge have been saying for years: inflammation may be a stronger predictor of heart disease than cholesterol. Clinician-authors like Dr. Gundry (who blame lectins/diet) have long argued inflammation is central, though their theories are more controversial and less trial-backed.
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.
Gundry is a huge quack. Listen to him on Dr Mike's podcast: https://www.youtube.com/shorts/LulcIT9XRFI -- Among many wtf claims, he claims that smoking is good for you because nicotine has antioxidants.
I think that’s a disservice to quacks - most of them are far better at dressing up their claims in something believable sounding. Gundry is just stark raving mad, it blows my mind that anyone gives him the time of day.
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.
> 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.
You should actually read the article. In particular:
> 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?
Careful. You are correct at what we want for primary prevent. However for primary prevention we need much larger sample sizes and thus data is much harder to get.
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.
> Lack of data doesn't mean the treatment won't work
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!
It’s not that lowering cholesterol does not decrease heart disease, but the fundamental problem of heart disease is not cholesterol, it’s the inflammation.
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.
For the last time. I am not saying that lowering cholesterol does not lower the risk of CVD. I am saying that it is oxidized cholesterol that causes CVD, and by lowering cholesterol you are also lowering oxidized cholesterol. Cholersterol good. oxidized cholesterol bad.
pubmed.ncbi.nlm.nih.gov/18625445/
Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis.
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.
Where we agree is that oxidation of LDL is part of the atherogenesis pathway.
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.
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.
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.
Your argument I responded to wasn't that the consensus of science is wrong, your argument was that the study is not valid because it was from the early 2010s
This is not a mainstream view of the science, and it's worth noting that this perspective is also not supported by the OP or by the JACC article that it's citing.
It's true that most doctors and pharmaceutical companies maintain that statins are effective. But there are plenty of statistically educated people that don't think they have much of an effect on all-cause mortality.
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.
> This is not a mainstream view of the science, and it's worth noting that this perspective is also not supported by the OP or by the JACC article that it's citing.
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.
The view among "authorities" is certainly something I find relevant in assessing a highly opinionated but thinly sourced medium article from someone who, respectfully, I've never heard of and know nothing about. Certainly it would be defeasible by a closer look at the research itself. But, barring that, it's a very useful heuristic.
I'm not suggesting you should take the medium article at face value either. Just that if you don't know enough to evaluate the evidence, you don't know enough to dismiss any particular opinion.
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.
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.
yes they do. for one thing you do not make the rules around here; no one cares what you think counts as suitable grounds for arguing. For another, yes, authority has some merit. Doesn't make it fact, but certainly the prior we ought to assign for "medical authorities are correct" is quite high. Not certainty, but pretty confident, all else being equal.
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.
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.
as others have noted, you seem to be unaware of what exactly the fallacy refers to. You might want to look it up. It is not "citing an authority at all" but rather "citing an authority's opinion as though it were logical fact". Which nobody is doing here.
> 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.
... What is going on? Yes, that's what it means, that's why I used it. Notice it does not say 'lie' or anything directly synonymous with lying. It's related, sure, but not the same.
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 is no logical fallacy in play here. Nobody is saying “the argument is wrong because of who said it”. 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: because the consensus is usually right.
> There is no logical fallacy in play here. Nobody is saying “the argument is wrong because of who said it”.
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.
Well yes, exactly: it's just consensuses all the way down. Which is just another way of saying "I feel like it's right and you're wrong, even though I have no actual evidence either way."
You are confusing what "Appeal to Authority" fallacy is. Namely you are ignoring the fallaciousness of it.
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 Medium blog you linked has 9 citations and none of them are actual scientific research. They're all news articles.
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.
Any cardiologist will tell you statins have saved millions of lives. And that they also have side effects that make them not an option for a significant chunk of the population.
Statins are not evil and they're not a scam, but we definitely need to replace them with something better.
> 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.
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.
Not really, the evidence that ldl causes heart disease and statins prevent deaths is very, very, very strong (lots of clinical trials, lots of causal evidence e.g. Mendelian randomization). LDL is extremely harmful!
So you are saying the human body manufactures a substance that is extremely harmful to the body. And yet lowering it artificially can lead to issues such as loss of short term memory. The body needs cholesterol! You could qualify your argument by saying that excess LDL is harmful.
The body needs SOME. Evolution doesn't care about when you die, just that you reproduce first. Even the highest cholesterol cases generally have kids old enough to have their own kids before they die. That is enough for evolution to not care.
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.
The body can produce needed cholesterol locally just fine. The PCKS9 inhibitor trials show that having basically no serum LDL is not harmful. People that have the genetic mutation that results in no PCKS9 have extremely low rates of CVD
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?
> The cholesterol to heart disease link is one of the best attested in medical science
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.)
It's a bad blog post for sure. However, I've a few smart people say that lower cholesterol may not be what makes statins powerful: it's the anti-inflammatory properties. I'm too lazy to find papers right now.
Yes, there is certaintly data to make that argument. The argument that inflammation is a better predictor of heart disease than cholesterol is a reasonable one. On the other hand the argument that cholesterol is not a good predictor of heart disease and cholesterol lowering therapy is a fraud is not reasonable in the face of the evidence.
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 can't be bad unless the original sources it cites 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.
Age-standardized cardiovascular mortality dropped steadily from 1975 to 2010 (with no particular discontinuity when statins were introduced), and has not budged since 2010.
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.
> Age-standardized cardiovascular mortality dropped steadily from 1975 to 2010 (with no particular discontinuity when statins were introduced), and has not budged since 2010.
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.
> The ACC is now recommending that everyone measure inflammation (specifically, hs-CRP)
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.
Do you have a link to an article that covers the history? In the time that I've been following this topic (about 10 years), hs-CRP has been the go-to biomarker of inflammation. It'd be interesting to learn about the process required to get there.
CRP and its subtypes have been known since 1930 as markers of acute inflammation such as following disease or injury. The measurement of chronic systemic inflammation is more difficult, because it involves lower levels of the biomarkers. So for example CRP levels increase by a factor of thousands when there is an infection, but in chronic systemic inflammation are elevated much more subtly. I don't know a great historical review but this "Nature Perspective" from 2019 seems pretty good:
For decades, LDL cholesterol has been the main target in preventive heart health.
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).
Thanks for the summary! I haven’t read tfa yet, so my apologies if this is answered in there, but: does this mean that we’ve already reduced the contribution from cholesterol to events? Or that cholesterol was simply associated and not causative? I imagine the truth is somewhere in between, perhaps we can guess that’s it’s 70% due to one and 30% due to the other?
It's more the former -- we've gotten so good at detecting high cholesterol and reducing it, that the majority of residual risk is now in the other factors.
(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.
Before you assume that LDL isn’t a good biomarker, read the entire article. Specifically this section:
> 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).
There have always been people with high LDL who lived to a very old age and finally died of something other than a heart attack (nobody knows why). Still high LDL after controlling for everything we can think of (cholesterol is cheap to measure so we have a lot of data!) is a strong sign of a future heart attack and so anyone with high LDL should talk to their doctor: there is good reason to think statins will reduce your chance of a heart attack. Which why we measure it and control it.
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)
LDL is a proxy measure that's cheap and easy to measure. It's widely used for screening despite not being perfect, which confused some into thinking it's the one and only thing measure of CVD risk. It's not, though. Many of the tests we look at are proxies and markers, not actually the sole factor for a disease.
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.
My cholesterol is (frankly) through the roof. My GP wanted to start statins immediately. I pushed back and asked what the big deal was -- my RHR is low, BP is normal, my weight is fine, I have an active lifestyle, and my diet is fine. They explained that the cholesterol might build up a blockage in my heart, and that higher levels meant higher increased risk of that. So I asked whether we could just check and see if that's actually happening, and you can! It's a calcium scoring test, and it cost me $150.
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.
You're probably a "lean mass hyper-responders", a phenotype which is actively investigated, initial paper:
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.
Same story here (though it cost me more - insurance refused to cover it because I did not meet the criteria [0])
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...
Calcium scores only reflect calcified plaque - not soft plaque. CTTA is what you need for that.
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.
Calcium scores only show calcified plaque - not soft. You need a CTTA for that.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10920137
LDL is almost always talked about as a singluar thing, even in scientific studies when LDL comes in several flavors.
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.
This doesn't really seem to pan out in reality. Often people with small dense LDL have it as a result of other risk markers. There's a good discussion here - https://www.youtube.com/watch?v=kplh30RmYo8 - the long and short of it is that when you perform mutual adjustment for number of particles, both large and small LDL particles are associated with a fairly similar risk. But if you have the same mass of cholesterol in two individuals (LDL-c) and one has SD LDL and the other has LB LDL, the latter has fewer LDL particles and therefore lower risk, so it can appear that LB LDL are less risky if you're only measuring cholesterol mass.
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.
The Jupiter trial clearly stated that those with low hs-crp didn’t benefit from LDL-C reduction, only those with high hs-crp had reduced CVD events due to LDL-C reduction.
PCSK9 inhibitor trials have shown significant benefit for reduction in CVD events independent of whether or not the inhibitors lowered hsCRP. Ezetimibe makes an impact on events without reducing hsCRP when administered on it's own. (But it is generally administered with a statin, and it seems that the combination does result in lower hsCRP than a statin on it's own)
https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/ https://pubmed.ncbi.nlm.nih.gov/36779348/
The claim I was addressing was that we don’t have evidence of statin efficacy for primary prevention. My point was that JUPITER seems to be evidence this isn’t the case.
> Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.
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...
> If you have normal cholesterol though - we have long known that people with normal cholesterol also have heart attacks.
Just to continue on this line, we also know that people with a genetic disposition for low cholesterol have a significantly lower risk of coronary heart disease than people with ostensibly normal cholesterol levels. It is one of the most proven, obvious correlations (more cholesterol increases the incident of CHD) in medicine.
Some snake-oil merchants, usually pitching a book or supplement, have often tried to muddy the waters by pointing out that someone at death's door often has very low cholesterol (they usually aren't eating, and cancer often "eats" cholesterol and leads to low levels), trying to then extrapolate this out.
These people with genetically low cholesterol, however, have other issues. Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. Many individuals with FHBL develop an abnormal buildup of fats in the livercalled hepatic steatosis or fatty liver.
You have to understand the point which you’re not yet able to put in your head. Yes it is true that lowering cholesterol lowers cardiovascular disease. No one here is disagreeing with that. What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease. I don’t know why this is so hard to understand. Lowering inflammation not only would reduce cardiovascular disease, but also cancer, arthritis and a multitude of other diseases.
> What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease.
interesting idea which I have heard before. However so far as I can tell we don't know if it is true. It seems to fit the evidence that the two are independantly causes of heart attack, when combined it is worse.
maybe someday science will figure this out but it is not easy and so will take a while. Until we do I avoid saying things with high confidence.
Cholesterol is more of a proxy "smoke" or "firefighter" measure than a measurement of the actual fire. It's very much a wet streets cause rain kind of thing.
Artificially eliminating the firefighters doesn't necessarily mean you've solved most of the problem.
Heart disease is a far more complicated problem than "cholesterol" or "cholesterol + inflammation", but humans and patients mentally gravitate to silver bullet thinking, which makes it really hard to work with. One interesting measure I've encountered is the lipid clearance rate, but it costs something like +$20k to measure and is not something a doctor can order from a lab; it's typically only performed in research settings.
This isn't necessarily true. High content of certain cholesterols in the blood does cause heart attacks. It doesn't just indicate it - it actually causes it.
And, we have shown the mechanism of action. Certain cholesterols will build up on artery walls, constraining the flow of blood. When there is too much build up and/or the vessel is too narrow, blood can be constrained too much, causing loss of blood flow and therefore oxygenation. The heart has MANY capillaries and requires a lot of oxygen.
This is really for real.
Comments like these just aren't based in reality. LDL levels are not a proxy or a wet streets cause rain. We even have a strong understanding of the mechanisms in which cholesterol causes things like heart attacks, strokes, peripheral arterial disease, etc. etc. etc. Something has to deposit plaque in your arteries.
Yes, from a mechanistic standpoint, inflammation is also an important causal factor. Lp(a) is also an important factor for people that are genetically predisposed to high levels - it also deposits plaque, and is one of the reasons ApoB is recommended. Most people don't have worrisome Lp(a) levels but enough do that we've been missing them, and we now also have good treatments for them - PCKS9 inhibitors reduce it by ~1/3rd, and we have Lp(a) specific medications in phase 3 trials that are even stronger.
But we know that statins work. This is some of the most established science in health. I keep seeing claims in these comments from people stating otherwise, but it just doesn't match reality.
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 this is why it's sometimes worthwhile to read the entire thread. Thanks for writing.
I believe the JUPITER trial showed this. If I remember correctly you needed high inflammation for high ldl to matter in cardiovascular events.
PCSK9 inhibitors don't universally lower hsCRP ( https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/ ) but do lower adverse cardiovascular events https://pubmed.ncbi.nlm.nih.gov/36779348/
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
>These people with genetically low cholesterol, however, have other issues
Neat.
>You have to understand the point which you’re not yet able to put in your head
Nowhere did I ever dismiss other causative inputs. All I did was reply to some probably-listen-to-chiropractor people who sure are trying incredibly hard to downplay cholesterol.
If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
Why don’t you stop your appeal to authority arguments and focus on the facts.
It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
If that is not interesting to you then you have an odd bias. I merely saying that inflammation is the risk factor that matters more than high cholesterol. You can lower cholesterol for someone who has high inflammation and reduce heart disease, but reducing inflammation is more important overall.
>If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
This is such a silly statement I'm not sure where to begin. Plenty of people smoke and drink and don't die of issues related to smoking or drinking, but smoking and drinking are bad for you.
Individual response to things varies. No one reasonable is going to say that because such and such person did X, Y, Z things that we know are bad and didn't have a negative outcome that we must flip the script on if those things are bad are not. Exceptions exist for a wide variety of reasons.
> It’s not that I haven’t died yet either. My calcium artery score was zero. I have no plaque in my arteries and I’ve had high cholesterol for probably 30 years of my life because of my genetics.
Calcium score does not tell you how much plaque you have in your arteries - it tells you how much calcified plaque you have in your arteries. This is NOT the same thing. You need a CCTA to tell if you have soft plaque or not.
I'm sorry, but you're just severely misinformed here and spreading all sorts of dangerous misinformation all over the comments here.
> If one person with high cholesterol does not get heart disease then cholesterol is not the problem. Fact. Logic.
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?
You’re an analogy is horrible
You’re comparing cancer to LDL. So you’re literally saying LDL is like cancer in the body. That’s ridiculous. The body does not need cancer, but it does need LDL to transport fats around the body.
And for your grandfather, yes, smoking does not cause cancer, smoking increases the risk of cancer, and cardiovascular disease, but there are other factors that play into that including nutrition and genetics.
Do you understand the distinction between increasing risk and causing?
This is the problem with western medicine, the constant search for a single cause disease because It’s not so complex that a non-holistic person can understand it.
If I was a legitimate scientist, I would look at your grandfather‘s case in curiosity and amazement. What was it that he did that proved him immune to the ravages of smoking? Do you know there were some people that had HIV that did not end up with AIDS? And the good scientist use those anecdotes to find a cure for AIDS and the current treatments that are now making people live long lifetimes with HIV.
> The body does not need cancer, but it does need LDL to transport fats around the body.
Of course the body needs cancer.
Cancer is your own bodies cells. They're essential for you being alive. And, cells with damaged DNA train and hone your immune system.
You have millions of cancer cells in your body right now. Your immune system is killing them as we speak.
If a few happen to slip through, then that's we would say you have cancer. Why might they slip through? Your immune system makes mistakes. Because everything makes mistakes.
> What was it that he did that proved him immune to the ravages of smoking?
Um, nothing?
Is this your first day on Earth? Life is not an algorithm.
Everything is risk, everything is probability. Smoking increases your risk. It doesn't give you anything.
Your HIV and AIDS argument is just fucking stupid. Sorry to be blunt.
Yes, SOME things are A -> B. That is an extremely rare exception to the rule. Extremely. That almost never happens.
Like, if I drive fast, I might die. Might. Its not a garuantee.
I can drive 150 every day and live, or drive 10 and die immediately. That's life. Welcome to risk and probability. That's just how things work.
Having LDL and no heart disease doesn't prove anything to anyone. That doesn't prove LDL doesn't cause heart disease.
[flagged]
LDL levels is too complex to be used as the litmus test it has become.
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.
Discordances like this between LDL-c and ApoB are one of the reasons many lipidologists are pushing for LDL-c measurement to be replaced with ApoB.
(OP here) LDL is still a good biomarker, but ApoB is a better biomarker for the same undelrying risk factor -- each atherogenic particle (LDL, VLDL, IDL) has exactly one ApoB molecule.
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.
Goodlabs prices:
https://app.hellogoodlabs.com/book-tests
So no, I wouldn't call $190 "pretty low", lol.Their comprehensive men’s panel is $200, which seems like the most comparable package. (The list of biomarkers above is a subset of the ones in our panel—obviously if you remove biomarkers, you’ll end up with a cheaper price.)
Unrelated to the topic, but does anyone know if an equivalent service (à-la-carte blood testing with online booking) is available in Europe, specifically the Netherlands (or France) ?
Can't vouch for any of these, but quick search shows:
https://labplusarts.nl/
https://www.bloodtesting.nl/
https://curitt.as.me/schedule/7b51cc60/appointment/70269915/...
https://www.easly.nl/en/personalised-blood-test/
Anecdotal advantage that I've heard of but not verified.
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.
Don't you sign something to the effect that you have not hidden testing like this that you are aware of?
And how would they know?
True - they wouldn't unless it is discovered and disclosure is mandated by a legal process. otoh - OP could provide a service where these results are completely anonymized if the person requesting the test so desires.
FYI the above poster is the founder of the company selling these tests (EDIT: He edited his comment to include the "OP here" intro after I posted my comment. Thanks!)
> 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 updated the above post to say (OP here). I thought it was fairly clear from my phrasing of "we offer the tests as cash pay", but never hurts to be even more explicit.
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 $190 panel. We've actually dealt with this exact situation in the last month, since every so often labs will make a mistake when they process the order (we obviously fix these situations). Perhaps the insurance companies aren't sane (a topic for another day), but this is unfortunately how the system works today.
Commenting to add - Insurance negotiated rate may actually be 1500$. If it is and they charge insurance 1500$. They legally cannot charge an individual a different or lower rate. Even if that person doesn’t have insurance and offers to pay cash.
This is one of those weird horrible traps health insurance puts you into. OP may charge insurance 1500$, 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.
Why would the insurance pay only 20% if it's a negotiated rate?
The problem I'm seeing here in Norway is that the bar to put people on statins is way too low given the severe side-effects and likely consequences of long-term statin use, even low doses.
I think LDL is a good biomarker, just not in isolation, and especially not a "one-size fits all" metric for individual humans.
I’m surprised by your strong wording. >”… severe side-effects and likely consequences of long-term statin use, even low doses.”
Could you provide a few reputable clinical outcomes studies to support your statements? I was unaware of these risks.
For one: https://pmc.ncbi.nlm.nih.gov/articles/PMC2949584/
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.
This just isn't true. Modern statins have extremely good efficacy to side effect ratios.
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.
It should be extremely easy to take this into consideration, and create cohorts of people who were not on a statin.
I'm quite sure we would still see that cholesterol is useless and that inflammation drives everything.
We have all sorts of RCTs, blinded studies, placebo controlled studies, MR studies that look at genetics, meta-analysis, etc. etc. etc. that all support the causal link of cholesterol... I've linked literally dozens of these in the comments for this article. If you care, feel free to look at my recent comment history - it's all in there and all my claims sourced.
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.
LDL has a u shaped association with mortality , just like bmi. Statins have a lot of side effects also, lots of muscle toxicity.
LDL and BMI's u and j shaped curves on all cause mortality disappear when you start controlling for other factors like a variety of diseases. Cancer, kidney disease, AIDS, etc. Lots of people end up with very poor nutrition when close to death from these diseases and end up with low bf%/bmi and LDL levels.
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.
the number needed to treat for a benefit from statins is high and the absolute risk reduction small.
Please stop spreading misinformation about life-saving medication. This is simply untrue.
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.
1. Lowest mortality is with ldl of 140, not lower/. https://www.bmj.com/content/371/bmj.m4266
2. Guess what the relative risk of myotoxicity is with statins.
> 1. Lowest mortality is with ldl of 140, not lower/. https://www.bmj.com/content/371/bmj.m4266
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.
> 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.
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.
My favorite definition of heart disease is "when circulating fats in the blood (lipids) are pushed by a driving force (blood pressure) into a vessel wall that is vulnerable (endothelial dysfunction)." IMO this gives a good mental picture of how all of these risk factors fit together.
But if they have lower cholesterol and still have a heart attack, then certainly the causal link is not quite there. It seems you’re suggesting it’s a good proxy measurement if untampered by statins though
I personally have naturally very low cholesterol and also had a heart attack in my 30s. There are a handful of case studies published of other people in this scenario but it is a rare enough scenario, and it is vanishingly rare to have years of reliable cholesterol results without known high risk.
I'm not sure I follow - is this what you're saying:
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.
Correlation is informative, but neither necessary nor sufficient for causation.
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.
We could grant all that for the sake of argument but it wouldn’t interact with anything I said.
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.
Ah I see what you mean. Thanks for clarifying
Welcome! Thanks for being understanding.
Statins are generally administered after decades of exposure to high cholesterol/ApoB.
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.
> 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?
In medicine, “mediates” is mostly synonymous with “facilitates”. So ‘lifelong exposure to cholesterol facilitates atherosclerosis’ - mediates is a bit softer since health changes often involve multiple pathways and can be impacted by many other processes.
There is a detailed lipid panel (Lipofraction NMR) as along with the HDL/LDL/TriG estimates they get today. There is a lot more detail in there. Statins help reduce LDL but the detailed lipid panel may still show a very high level of LDL-P and Small LDL-P which still increase risk.
If you're going for more testing, I would definitely suggest the lipofraction.
The most recent evidence is that if you’re measuring ApoB and Lp(a), you’re capturing the same information as fractionation (with the bonus that the former two are slightly faster and cheaper at most commercial labs):
https://academic.oup.com/eurheartj/article-abstract/46/27/27...
If you're already on statins, they may be lowering your hs-CRP. Still have that conversation with your dr.
when a measure becomes a target etc etc
LDL has always been both a worthwhile measure and target. It's not perfect as a measure - it doesn't account for Lp(a), for example, and why ApoB is a better indicator for the atherogenic particles portion of the equation - but we know that lowering LDL lowers the risks of ASCVD and results in better health outcomes. I've linked quite a few studies over the comments here backing this up with huge quantities of data points.
ApoB is the best measure we have.
You forgot to mention that statins are an anti-inflammatory as well. This argument itself fails on that
PCSK9 inhibitors do not universally lower hsCRP but still reduce cardiovascular events.
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...
https://www.nejm.org/doi/full/10.1056/NEJMoa1604304
https://pubmed.ncbi.nlm.nih.gov/23083789/
Yes, LDL is the best we have since they won’t bother to measure oxidative stress nor inflammation in the human body.
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.
> But lowering your LDL does not prevent heart disease. There are many many people with normal LDL who have heart attacks.
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.
Lowering LDL isn't equivalent to a seatbelt. A seatbelt is a safety device that performs a function in an accident.
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.
>Lowering LDL doesn't actually do anything on its own
Is this some sort of weird philosophical statement? Because, of course, it's completely nonsensical, and completely at odds with all data on this file.
Lowering LDL reduces CVD incident rates, with no other interventions. People with genetically low LDL also have lower CVD incident rates. This is extraordinarily well proven.
So it sure seems -- you know, 100% of medical science -- that lowering LDL does "something".
The human body is a complex machine, however, and CVD is multifactorial, and for CVD to develop the current thinking is that you need inflammation and high cholesterol over decades. Inflammation can be caused by things like high blood pressure and the like. But everyone has inflammation to some degree as a facet of living, and the easiest component of that to treat (not just measure) is LDL.
And yes, there is an industry of cholesterol denialists, among whom there are just loads and loads of chiropractors. These clowns have built armies of poorly informed disciples that run to HN to tell us that cholesterol doesn't matter and lowering LDL doesn't do anything.
> People with genetically low LDL also have lower CVD incident rates. This is extraordinarily well proven….. you need inflammation and high cholesterol over decades.
We know that low LDL does not prevent CVD. Therefore we know that you do not need high cholesterol over decades.
He said LDL does not do anything on its own, meaning that there’s another factor that causes oxidized LDL, which triggers plaque formation and heart disease. As I pointed out in another post over 75% of people who have heart attacks have normal LDL.
I get my CRP measured every year. I have zero inflammation and I am in my late 50s. So not everyone has inflammation.
You’re saying a lot of nonsensical stuff in your comment like high blood pressure causes inflammation , which tells me you are not serious in this discussion. Because that makes absolutely no sense.
Localized foam cell activation and cytokine signaling does not necessarily raise hsCRP yet allows for continue plaque deposition. This is a very well understood mechanism.
No one knowledgeable here is saying that inflammation isn't worth paying attention to, but people acting like because inflammation is also important that LDL does nothing just aren't living in reality.
Your comment about blood pressure actually reveals more about your knowledge here than the person you're replying to.
FDG-PET is a signal we can use to detect tissue inflammation, and we know that higher blood pressure is highly correlated with increased FDG-PET in arterial walls:
https://pmc.ncbi.nlm.nih.gov/articles/PMC6994784/
High blood pressure is also feed-forward loop with Angiotensin, which increases inflammation:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3377325/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4192119/
Blood pressure results in shear stress to your arteries. This results in several things that amplify Angiotensin II and NF-kB activity, including expoosing adhesion molecules which then results in foam cell activation and cytokine signaling, etc.
It is quite well established that high blood pressure will contribute to increased inflammation.
>He said LDL does not do anything on its own
It's like saying a flying bullet can't do anything on its own. It is a meaningless statement.
>As I pointed out in another post over 75% of people who have heart attacks have normal LDL.
The actual study authors were advocating for lower LDL guidelines, particularly among the elderly.
A heart attack is the destination, not the journey. What someone's LDL was at admission for a heart attack says literally nothing about their state for the decades before. In actual studies tracking cholesterol, even over a five year period lowering LDL has a potent beneficial effect.
>You’re saying a lot of nonsensical stuff in your comment like high blood pressure causes inflammation , which tells me you are not serious in this discussion
Hypertension can cause endothelial inflammation, leading to blood vessel damage and promoting the release of inflammatory mediators. This is extremely well documented, and it's why getting hypertension under control medically is considered extremely important in the CVD battle. Inflammation and hypertension often are found hand in hand, and there is uncertainty over the cause and the effect, but strangely controlling hypertension alone dramatically reduces inflammation. Weird, right?
>I have zero inflammation
Sorry, but LOL. Not only is that a singular and very narrow test, inflammation is literally just a facet of living. As is oxidization. There isn't a single human alive with "zero inflammation", nor is there anyone that has magically non-odidizing LDL.
If you don’t understand the difference between acute and chronic inflammation, there is no longer any reason to continue this conversation with you. Yes, I apologize because I didn’t specify the difference, but I thought you would be intelligent enough to know the distinction.
Sure thing. I'm sorry I'm just not intelligent enough to have a discussion with an expert like yourself.
Lowering LDL is one of the best preventative measures we have for ASCVD.
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.
How can inflammation be measured?
I am sure there are other means, but I always thought C-Reactive Protein levels were the standard measure.
>But lowering your LDL does not prevent heart disease
Literally one of the most proven truths in medical science is that LDL levels has an almost directly relationship with CVD risk over the long term. Someone with low cholesterol can of course still have CVD, but their odds are much better than someone with high cholesterol. And of course the damage from cholesterol is additive, so the earlier you control LDL, the more of a benefit.
>A new national study has shown that nearly 75 percent of patients hospitalized for a heart attack had cholesterol levels that would indicate they were not at high risk for a cardiovascular event, based on current national cholesterol guidelines.
The damage from high cholesterol happens over decades. Yet the people who actually have heart attacks are often older.
So yes, if gramps spent his life with high cholesterol but now he barely eats and is sedentary, he might have low cholesterol now but that says literally nothing to what you're claiming it does.
Yes, much like wet streets are a high predictor of rain. Or smoke, firefighters and wood are a high predictor of fire. The firefighters are not causing the fire, neither do the wet streets cause rain. This is what people are trying to tell you. If you remove the firefighters only, then you might make it worse. If you do something to cause the firefighters to go away, probably because there isn't a fire anymore, then you did the right thing. The important thing is not to goodhart's law yourself into doing the wrong thing.
This would be a fair analogy if we didn't have studies with a temporal component, but we do. We look at individuals before they get disease then track them over time to see what predicts disease. So we can see, per your analogy, that the fire is there, then the firefighters turn up.
[flagged]
No. They’re saying that damage is cumulative over a lifetime - plaque deposition - so that a point in time snapshot of LDL says little about lifetime exposure. If I live my life with high LDL and only get on statins at 65 I might have low LDL when I have a heart attack but the damage came from the decades of high LDL.
The current guidance from the AHA and NLA is that lower is better for as long as possible.
Lower cholesterol helps but lowering inflammation helps everyone. As I’ve said in another comment over 75% of people who have heart attacks have normal LDL levels.
https://www.uclahealth.org/news/release/most-heart-attack-pa...
And lower cholesterol is not without its own risks. You need cholesterol to make hormones and things like CoQ10, which are important for our health. So what’s better? Lowering oxidative stress and inflammation or lowering cholesterol?
LDL levels at admittance do not tell us what their lifetime LDL levels were. But even your own link is arguing for lowering the the number at which we consider LDL levels risky.
PCSK9 inhibitors when coupled with statin therapy have gotten people to ~10 LDL without negative impact in clinical trials. The body is good at producing cholesterol where it needs it - it doesn't pass the blood brain barrier, yet the brain is full of it. It produces it's own, the same as quite a lot of other tissue
For hormones, de novo synthesis of cholesterol is a thing when it comes to steroidgenesis, as well as recycling and re-uptake. PCSK9 inhibitor studies specifically looked at this because of this concern, and found cortisol/aldosterone/testosterone/estrogen/etc. were not impacted by having very lower levels of LDL-C.
The issue with statins and CoQ10 isn't cholesterol - it's the mevalonate pathway. They block a reductase in the pathway and this results in lower serum CoQ10 levels. Data around if this is of any clinical relevance is a mixed bag, but this is easily supplementable if needed, and should not be a reason to not take life saving medication. PCSK9 inhibitors make large dents in LDL but do not impact CoQ10 levels at all because they do not impact the mevalonate pathway.
https://www.ahajournals.org/doi/10.1161/ATV.0000000000000164 https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/201... https://pubmed.ncbi.nlm.nih.gov/36779348/
As for which is better... lower both. Why wouldn't you want to lower all the causal factors you can? Statins even do this!
> lower cholesterol is not without its own risks
I haven’t seen any clear evidence that low blood cholesterol has actual risks, just hypothesizing. Is there any?
You have left multiple comments for the sole purpose of muddying waters. So HN would probably be better off if you didn't reply.
What did I "shout"? What are you even going off about? Don't project your angry fanaticism on others.
Further, your literacy is not my problem. Nothing in my comment was contradictory or confusing to anyone but you.
There is a theory that cholesterol elevates in response to circulating endotoxin (dead bacteria cell walls). Lipoproteins can bind to the endotoxin, and clear it or at least stop immune cells from reacting to it. This response increases LDL, but decreases the immune activity that would otherwise be created by letting the endotoxin circulate. So LDL is a defense mechanism against the body's own response to circulating endotoxin as well as the endotoxin itself.
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...
Why would a significant part of the population have dead bacteria circulating throughout their bloodstream? Bacteria live and die in the gut regularly, so it seems exceptional that parts of it would enter circulation and somehow avoid metabolism.
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.
Bacteria entering bloodstream is quite common it seems, gut is not perfectly sealed and less sealed because of bad lifestyle choices. I think the article points out that treating cholesterol doesn’t treat the root cause and possibly! ineffective in itself to lower heart disease risk as something else is causing direct health threatening problems.
This is all just a hypothesis, and a very new one. We know almost definitively that high cholesterol causes heart disease and lowering cholesterol lowers your risk of a heart attack.
Alcohol, NSAIDs, stress, obesity, or chronic inflammation
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.
Saw this the other day which may tie in with what you're saying? "Bacteria present in carotid arterial plaques are found as biofilm deposits which may contribute to enhanced risk of plaque rupture" : https://pubmed.ncbi.nlm.nih.gov/24917599/
That does seem related, but it suggests something even more unexpected, which is that live bacteria are forming biofilms in arterial plaque. So the LDL is picking up live and dead bacteria and then adhering to the side of arteries.
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).
Very interesting
I'm wary of trusting new health science from a company trying to sell me the cure to what they just discovered was the _real cause_ of my ills.
This article might be truthful, it might not. But it is absolutely trying to sell you something.
The article is merely summarizing new recommendations from the American College of Cardiology. You can read the source if you prefer it: https://www.jacc.org/doi/10.1016/j.jacc.2025.08.047
Thank you for linking. The first few paragraphs sound like this is kind of big deal, like print out and read.
I certainly get the skepticism. You might find the JACC article (which is an American College of Cardiology consensus statement) interesting, since the ACC is a neutral party here (and reviewed all the evidence around hs-CRP).
In fairness, the literature has been trending this way for a long time. Well before anyone had figured out a way to profit off of it.
Yes, and the internet has helped quite a bit with this. Instead of a small group of people having access to research through university or hospital publishing networks, everything circulates on the internet for anyone to look at.
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.
hs-CRP is well known as a useful biomarker and it is cheap to test too. If you look at page 13 of the GrimAge 2 paper, you'll see CRP is one of the factors most negatively correlated with their aging clock, in fact basically as strong of a negative impact as smoking. https://escholarship.org/content/qt6k46n006/qt6k46n006.pdf
This new news is about research published in the Journal of the American College of Cardiology.
It's definitely not some marketing fad.
Cholesterol can hide your inflammation.
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.
Does "inflammation" refer to a general systemic thing? Or does this refer to something specific such as tendonitis or inflammation due to injury?
This is a good question.
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.
Just thinking out loud here, but I wonder if the immune activity is not the problem, but some kind of destructive process that is triggering the immune response. A continuous onslaught of destruction tends to make things break down faster.
Other than a biomarker, does it produce symptoms?
The C reactive protein itself doesn't cause symptoms on its own. It's produced by the liver in response to signals from immune cells. It actually binds to bacteria in circulation, so if anything it helps. As a data point, it can vary by >1000x during the course of a disease, and won't be something that people feel or complain about separate from the other symptoms.
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.
Chronic inflammation (a general systemic thing) is the thing we're mostly concerned about for heart health. The hs-CRP metric itself will pick up both acute inflammation (if you get sick) and chronic inflammation.
Upvoted because I was going to ask the same thing: What is "inflammation" in this context?
hs-CRP is the specific biomarker
I have always read it as systemic. Which is why low carb diets seem to do wonders for a lot of people's cardiovascular systems, somewhat paradoxically. If you go really low carb (<20g / day), the first week or two you can lose a ton of weight, but much of it is water, which detractors point to as "well, you're not losing fat!" But, imagine what this does for inflammation. That is 7 pounds of fluid you are no longer carrying and pumping against. It's basically a gallon. The first round of keto I did, I lost a ton of weight the first month (~20 lbs), and my blood pressure plummeted to the point where I was dizzy all the time, and I had to supplement with salt and magnesium. I remember a study I read probably 15 years ago where they looked at cross-sections of arteries before and after starting a ketogenic diet, and there was significant reduction in inflammation after just a few weeks, IIRC. I just tried finding it on pubmed, but can't find the right incantation of search terms to dredge it up. There are countless studies like this.
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.
"But, imagine what this does for inflammation. That is 7 pounds of fluid you are no longer carrying and pumping against. It's basically a gallon. The first round of keto I did, I lost a ton of weight the first month (~20 lbs), and my blood pressure plummeted to the point where I was dizzy all the time, and I had to supplement with salt and magnesium."
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.
Could it be either of these studies?
“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...
What exactly does your diet consist in? What other adjustments have you made, e.g. in sleep or exercise?
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.
[1] e.g. https://doi.org/10.1093/advances/nmaa006
What if you're trying to put on muscle? I found it was very difficult to push myself to the extent that I wanted without high carbohydrate intake.
CRP is a protein produced by the liver in response to inflammation. Elevated CRP levels indicate inflammation in the bodY.
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.
> 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.
> Keep your oxidative stress low and you will not get heart disease.
if you take this advice literally, you should stop exercising
Yes, you are correct. Nothing wrong with walking, helps keep weight low and fat cells are a huge source of oxidative stress. Better to eat low calorie, high nutrient dense foods.
Easier said than done. Even microplastics have been liked to oxidative stress and inflammation.
I have genetically high cholesterol. But otherwise I exercise quite a lot and healthy. I’ve been told not to worry about cholesterol unless other indicators start to climb. So I just generally avoid high saturated fat foods (sat fat in food matters more to blood cholesterol than food cholesterol).
Have you measured your Lp(a)? It's the strongest hereditary risk factor for heart disease. (Each Lp(a) particle is essentially a "normal" cholesterol particle with an extra protein that makes it 6x more atherogenic.)
How old are you? I'm not a doctor, but my impression is treatment for cholesterol is not considered worth it until you are "older". Depending on how high, older can range from 35 to 50. (actually a better marker is probably when did your grandparents have heart attack, start treating somewhat before then). Which is to say get regular checkups because you will likely be put on treatment in the future, but not today.
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.
The guidance has been changing significantly over the past few years. The consensus from expert organizations is now that we should be lowering it far earlier.
https://www.lipidjournal.com/article/S1933-2874%2825%2900317...
To the point of the original article, the consensus is probably doing people more harm than good. My mother had a heart attack at 45. My brother died of a heart attack at 48 and my other brother had a heart attack at 47. My cholesterol has been over 200 for at least 15 years and I’m in my late 50s. My calcium artery scan was zero and all heart sonograms are perfect.
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.
Anecdotal data does not disprove the millions of data points from well controlled well structured RCTs that have been poured over by the brightest minds in the field.
The positive impact of lowering LDL is some of the strongest science we have on health.
You mean the positive impact of consuming statins. Consuming statins coincides with lower LDL so I can imagine people conflating the two variables. I'm sure taking statins also has other effects on the body.
No, I mean the positive impact of lowering LDL. Statins of course show positive impact, and yes, including from also lowering inflammation. But so do other drugs that lower LDL through other mechanisms, including ezetimibe, bempedoic acid, and pcsk9 inhibitors. MR studies on genetics also show that lower LDL even without other factors that reduce inflammation significantly reduces the risk of of negative ASCVD outcomes.
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 dismissal of anecdotal data is why science has been stalled and people are still sick.
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?
High LDL or Lp(a) on its own causes enough localized inflammation to continue plaque deposition. We can’t drive down every cause on inflammation to 0 to the point that there is zero plaque deposition at all in the presence of high LDL, there are just too many causes. Even temporary increases in inflammation from natural processes can deposit plaque is you have high amounts of atherogenic particles. And once they deposit, they begin to cause inflammation independently. Not all inflammation can be measured by hsCRP.
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.
Heart disease progresses over decades and there's no solid evidence it can be reversed. You don't want to wait til you're 18 months out from a heart attack to do anything. I don't think this is good advice
> Heart disease progresses over decades <...> You don't want to wait til you're 18 months out from a heart attack to do anything. I don't think this is good advice
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.
In my 40s
It would be worth checking to be sure your doctor is up to date. The other reply suggests younger is the latest - but I'm not a doctor.
> sat fat matter more to blood cholesterol than food cholesterol
Can you expand on this? I don't understand.
Eating excessive saturated fat is what your liver turns into too much "bad cholesterol" and what you need to watch if you're having cholesterol problems. Cholesterol in food doesn't usually translate to you having more cholesterol in your blood.
I would have to go dig up the source for this, but I believe that genetics play a role on how your body handles dietary cholestrol. For many it's not a problem, but for some it is.
Yeah, it's that and the relationship between dietary cholesterol and serum cholesterol isn't linear - once you're consuming a certain amount of dietary cholesterol, adding more doesn't make much difference to serum cholesterol.
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.
This is the study that finally confirms what a lot of people in the health/bio-hacking space have suspected for years! It’s not that cholesterol is irrelevant—it's still a primary risk factor—but it's clear it's only half the story.
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.
Is this an advertisement? There's a CTA for a $190 service above the fold.
It is, but as siblings note the evidence is real. You can purchase the test directly from Labcorp for $59 – https://www.ondemand.labcorp.com/lab-tests/inflammation-hs-c...
Note that the $190 panel includes not just hs-CRP ($59), 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.
Anyone know how weight lifting might be related to this?
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.
I dont know the direct answer to your question, and am not a Doctor nor researcher... but using a generally applicable health pattern -- it's important not to equate acute anything with chronic anything. Eg: Acute fat loss via exercising while fasting does not seem to relate to body composition changes over 12 weeks. Similarly the self protective process of hormesis seems to actually create greater health - like reactions to heat from sauna usages for example.
Fundamentally weight lifting should reduce inflammation, but at the same time I’m less certain about how things like protein powders or very high protein intake factor into this.
Weightlifting increases inflammation acutely, not chronically. But if you work out too much without enough rest, then the inflammation is chronic and that’s where the danger is. Over the long-term resistance training decreases CRP level levels when adequate rest is involved.
Everything has downsides. Exercise causes short term high blood pressure. Food generally decreases FMD. Etc.
Exercise in moderation is almost always worth it.
Exercise raises acute inflammation but lowers chronic inflammation
I'd guess this is persistent, systemic inflammation. So I, as someone with IBD, have higher levels of CRP, so am probably a prime candidate for this kind of early death (despite having quite good cholesterol)
I believe IBD only had a slight impact on all cause mortality figures.
is there something akin to a continuous glucose monitor but for inflammatory biomarkers? it would be so dope to be able to watch your body respond in real time to the foods you eat the way you can with a cgm
The closest thing I've seen is the antioxidant index from Samsung's latest Galaxy Watch: https://www.mobihealthnews.com/news/samsung-debuts-galaxy-wa...
It specifically measures carotenoids through the optical heart rate sensor -- you mostly get carotenoids from eating vegetables, and they do reduce inflammation.
Came here to asks this. This could unlock a super powerful feedback loop towards fantastic health.
It always did... even the way cholesterol recommendations have been aren't really good in and of themselves. The better marker is Triglyceride to HDL ratio, in terms of correlation to morbidity. Not total, not LDL by itself without quality tests.
Trig/HDL and LDL/HDL ratios are outdated science that have been superseded by our better understanding of the causative factors and our ability to drive LDL way lower than we could in the past.
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
28 years old, had a heart attack last weekend (inferior STEMi)
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:
Glad you're still with us! (And that you're seeing a cardiologist soon.)
Glad you're still with us, mate.
Was a hypothetical cause ever suggested?
I had vulnerable plaque rupture in an inferior artery that caused a 99% occlusion after thrombus formed over it
Very genetically predisposed to cardiac events unfortunately
Good luck to you, hope you keep on top of it. Do you know if you have high lp(a) out o curiosity? Curious what drives these events in cases such as yours.
I will soon, as a follow up from cardiologist.
My money is on it being within normal limits.
In my case, I got dealt a very, very poor set of cardiac genes. Everyone on my mother's side has had at least one heart attack, though they generally started around age 50.So statins lower LDL; what lowers inflammation?
Exercise.
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.
It's quite a lot harder than just taking a pill every day, of course.
Only because people drive everywhere. If you live in a well designed city you just walk everywhere and you don't have to do anything extra.
It's only hard because we make it hard.
I walk my kids to school every morning. And I walk to pick them up. It's a 10 minute walk to get them, so that's about 40 minutes of walking each day. I could drive and get there in 2 minutes then wait in a line. It would probably cut the time in half, but walking is better for the environment (noise, pollution, safety, wear and tear), me, and my relationship with the kids (we, y'know, talk while we walk).
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.
That's great - for me the problem is weather. Where I live it's hot, >80s Fahrenheit, >28 celsius, for 4 months a year. So unless I want to always be sweaty, I can't really walk more then 10 minutes at a time.
You sound like you live in the Midwest like I do.
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).
Carry a water bottle and take showers. Sweat is normal, if you don't like it wash it off.
There needs to be a shower where you're going, and you need to budget the extra time and change of clothes.
Folks seem to have forgotten about sun umbrellas as well.
And do the thing at dawn if you can!
In the US a large number of people have moved to suburbs in the south. On a bad year our lows are in the 90F range. Add in asphalt architecture and in the sun temps are commonly 125F+
Patient: "Doctor, it hurts when I do this." Doctor: "Then don't do that!"
Or get a dog.
It's not though.
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.
Walking for 30 min isn't going to do it either.
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%.
If someone goes from not exercising at all to walking 30 minutes a day, it will make a definite dent in blood pressure. Changing diet will add another dent. Walking for 90 minutes a day will make a bigger dent than 30. The degree of the changes reflects the degree of the results.
Exercise actually increases oxidative stress.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7498668/
What lowers oxidative stress is nutrition, specifically selenium, vitamin C, manganese, zinc, and copper.
I knew I should be eating more soil
Breathing also increases oxidative stress but no one is going to tell you to breathe less
Selenium can elevate your PSA, so stop taking it a couple week prior to a test. It also increases fluid production from the prostate.
Homeless are walking (exercise) miles daily 365/7 yet they are unhealthy. lol
There are often other comorbidities with being homeless.
I don't know man some of those guys are absolutely shredded. Maybe they're just platonists?
Diogenesists? Diogenesers? Followers of Diogenes?
I'm low on ancient Greek knowledge, what are you getting at?
Why would they be platonists? Diogenes was the Greek philosopher who shunned material things and famously lived in a barrel. Seems like that would be the ancient Grecian philosopher that might inspire some form of voluntary homelessness.
There's a (apparently un-substantiated[0]) claim that Plato was buff; "Plato" was apparently a nickname and meant "broad" in Classical Greek, referring to his wrestlers physique.
[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.
Ah fair, I meant in that they're homeless so they must live in their heads/in ideas which are more real to them (hence Plato), so they're shredded from always being active and outside.
I believe followers of Diogenes are called Cynics
Ah, yes.
Avoid allergenic foods, Highly processed foods. Get plenty of sleep. Manage stress. Avoid toxins like alcohol or smoking. Avoid chemical irritants including perfumes, dyes, fragrances in detergent or soap, ….
Not sure why this is downvoted, this is correct on all points. I've been on a journey to lower chronic inflammation and you would not believe how hard it is to find stuff that doesn't have "fragrance" or other mysterious potentially-inflammation-causing substances.
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...
One says
> 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.
from the heartandstroke.ca
> 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.
Sorry, where did you find that text? I can't find the words "mainly whole grains", or even the word "servings" anywhere on https://www.heartandstroke.ca/articles/the-anti-inflammatory... .. maybe you navigated to another page afterward or something?
You're right, I actually navigated to their dash diet page:
https://www.heartandstroke.ca/healthy-living/healthy-eating/...
Honestly that used to be a common midday break for me at work. 2 slices of bread per sandwich with ham and/or cheese inbetween the 2 I never gained weight and always ate a lot tho and as i got older i've become more active.
GLP-1s.
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...
I saw an interesting video that mentioned a study. Even though 10K steps a day is considered an arbitrary amount, this study found that level of activity counteracted inflammation.
https://youtu.be/bDGA82wts2g?t=2015&si=lmZeD_KE1F7TvOPA
Consider: https://doi.org/10.1016/j.bbi.2016.02.024
Click the link.
> Lifestyle: Anti-inflammatory diets (Mediterranean, DASH), regular exercise, smoking cessation, and maintaining a healthy weight all lower hs-CRP and reduce risk.
also they list a big list of drugs that are in various stages
Exercise,sleep,vitamin d, omega 3, curcumin
And avoiding putting stuff in your body that makes your immune system react like air pollution, microplastics, hyper processed foods
>And avoiding putting stuff in your body that makes your immune system react like air pollution, microplastics,
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.
Prednisone and other corticosteroids. They are not good to use long term for many reasons.
There is no free lunch or magic bullet (yet) to health. We're all going to die.
Lifestyle.
Not sitting a lot (more than 1 hour at a time), walking or cycling everywhere, not eating a kot of sugar/refined carbs..
Just to throw into the mix: apparently sitting in a hyperbaric oxygen chamber does. Who would've thought.
Low dose aspirin can lower inflammation.
Please be very careful with low dose aspirin.
I am 5 months into NSAID Gastritis. Would not recommend.
Yes, there is that risk. On the other hand there is the risk of stroke, which I am more scared of, which is why I take aspirin. What is the impact of NSAID Gastritis? How bad is it and can you recover from it?
If you have been prescribed the Aspirin then it’s important to continue or discuss with your Physician. But as I mentioned in another comment, there are gastro protective Aspirin pills available.
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).
How low was your dose? 75-125mg?
It was 75mg. Soluble, not gastro resistant ones.
I was taking a lot of Ibuprofen due to frequent illnesses while simultaneously needing to be healthy. I started to get terrible heartburn that caused me to hunch over at times. Tried dietary changes. Finally, I happened to read that this and ulcers is a side effect of NSAIDs. Switched to acetaminophen, and was generally more judicious about taking fever meds, and I haven’t had heartburn in months now.
Acetaminophen doesn't deteriorate the stomach lining like NSAIDs, but it also isn't anti-inflammatory. It's an analgesic and antipyretic.
Yes, I mention this all in the context of needing a fever reducer
Did you take your Ibuprofen with some food?
The conventional wisdom is that low dose aspirin prevents heart attacks by lowering the tendency for blood to clot. I've long had a theory that it was the anti-inflammatory effect that had the greatest benefit.
Potentially inhibiting IL-6 or reducing Lp(a). We'll get an early glimpse from some robust Phase 3's next year. These have been in the works for several years with tens of thousands of patients enrolled - it'll be an exciting set of readouts.
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...
Improvements in diet, stress, and environment.
I have never understood how one supposed to reduce stress. For me, stress is a signal that there is some threat in my environment. Such threats are often outside of my control. How is one supposed to reduce something that he or she has little control over?
Well, not with that attitude. Surely you've seen people on life that you felt overly stressed themselves. It's not just a natural bodily reaction, how you react to the reaction. Some people can spiral out of control with stress, amplifying it. Other people can relax and not let it get to them.
Try meditation? Not the religious stuff, just breathing exercises and trying to clear your mind
> Some people can spiral out of control with stress, amplifying it. Other people can relax and not let it get to them.
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?
It is more complex than just a threat in our environment.
Huberman has done a few episodes on it: https://www.hubermanlab.com/episode/tools-for-managing-stres...
I have heard of this man before, but I am not well versed in his podcast. Thank you for sharing this though. I will check it out.
and sleep.
I'm not a doctor, but I am passionate about this stuff in my own life.
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.
Statins also have an anti-inflammatory response.
I am extremely skeptical about the need for this kind of shotgun "health marker" blood panel test. Even granting the premise that whatever ML algorithm they use to interpret the results is at all accurate, the upshot is unlikely to change the general recommendations regarding heart disease anyway (control blood pressure, stop smoking, manage diabetes or pre-diabetes, maintain a healthy diet and meet the physical activity guidelines).
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.
FWIW, the linked article shows a specific biomarker that would change both medication and lifestyle, i.e., something you’d act on.
The panel from the company above (I’m a co-founder) includes a review with an MD (not just an algorithm).
Thank you to the reply; the fact that there is a qualified human in the loop to review test results is very encouraging. I stand corrected on my initial assessment.
It’s important to note that hsCRP and C Reactive Protein are 2 different tests.
Curious about infliximab being unhelpful or even harmful for cardiovascular risk; I'm not sure if there were any confounding factors re. people on infliximab not generally being in great health to begin with. But back when I was on infliximab I had some not-awesome systemic side effects, so I wouldn't be chocked if it's just not great for your cardiovascular health in general. (And that's still probably a worthwhile tradeoff if you're the kind of person who's being prescribed infliximab.)
If you don't mind me asking, what was your like on Remicade (and/or what you swapped to)? I suppose I have the option of taking a biologic (not Remicade) for an immune mediated condition, but I can't help but shake the feeling that the cure might be worse than the disease in my particular situation.
I don't mind at all! I started on Humira, switched to Remicade, now on Skyrizi. Remicade worked better than Humira for me, but it's a much stronger drug (and I worked my way up to a higher-than-default dose), so I was prone to some weird skin infections that I hadn't had on Humira despite both drugs acting on the same mechanism, and my immune system was weaker overall. Nothing serious, just annoying. And I wasn't actually responding that well to Remicade overall.
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/
Thank you for your response.
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.
That all makes sense! If your skin stuff is relatively mild and isn't causing you too much trouble, a topical approach seems warranted (and is certainly a lot cheaper). That said, if it ever does get worse to the point where you're in genuine distress, keep in mind that the psoriasis-only dose of a drug like Skyrizi is a lot lower than the big fat dose I take for Crohn's disease, and less frequent as well. Also keep in mind--and hopefully it doesn't come to this--that psoriasis is highly comorbid with both Crohn's/colitis and arthritis, so if you start to experience worsening digestive issues or joint pain, definitely get those checked out. The silver lining is that if you do experience comorbidities like that, finding the right treatment (usually but not always a biologic) can knock them all out at once.
(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!)
I am an Empirical Health customer, and the app has numerous bugs. Please, fix them before blogging! Thank you for your attention to this matter. MAKE APPS GREAT AGAIN!
Hi! Happy to help -- can you send me your debugging code (under Settings) if you haven't already? I'm bmb@empirical.health.
Thank you! Just emailed you with the debug code. By the way, on the debug code screen, it says that my push notifications are off, but I was never asked to enable them within the app itself.
This isn't surprising, and its refreshing to see more research that questions the cholesterol hypothesis finally gaining some traction.
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.
This doesn't question the cholesterol hypothesis. The link between higher ApoB and increased risk of CVD and death is one of (if not the) best understood and well researched exposure/outcome relationships in human health research.
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?
This paper isn't directly challenging the cholesterol hypothesis but it is a step in that direction. 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.
No, it really isn't.
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...
https://www.nejm.org/doi/full/10.1056/NEJMoa1604304
https://pubmed.ncbi.nlm.nih.gov/23083789/
I didn't say there can't be multiple causal factors, and in anything related to biology I would expect there to be multiple factors.
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.
The cholesterol hypothesis certainly leaves room on the table for multiple causal factors, and from very early on we knew that inflammation was key to plaque actually being deposited on arterial walls. The cholesterol hypothesis has always been that serum cholesterol are linked and that decreasing serum cholesterol significantly reduces heart disease. It is not that serum cholesterol is the sole source of heart disease.
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.)
Why would that raise questions about whether cholesterol levels are correlative rather than causal?
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.
That isn't the a good comparison. You are describing two pathogens that can both be found to be highly correlated to risk of lung cancer in isolation. A smoker with no known asbestos exposure is still more likely to get lung cancer than a nonsmoker, and visa versa.
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.
What I’m arguing against is the form of the argument you’re making when you say:
> 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?
https://www.health.harvard.edu/staying-healthy/inflammation-...
Interesting that official recommendations are catching up to what some clinicians on the edge have been saying for years: inflammation may be a stronger predictor of heart disease than cholesterol. Clinician-authors like Dr. Gundry (who blame lectins/diet) have long argued inflammation is central, though their theories are more controversial and less trial-backed.
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.
Gundry is a huge quack. Listen to him on Dr Mike's podcast: https://www.youtube.com/shorts/LulcIT9XRFI -- Among many wtf claims, he claims that smoking is good for you because nicotine has antioxidants.
I think that’s a disservice to quacks - most of them are far better at dressing up their claims in something believable sounding. Gundry is just stark raving mad, it blows my mind that anyone gives him the time of day.
wow, that seems quite insane
"Less trial-backed" is doing some heavy lifting here afaik, is there any reputable clinical evidence of this?
Very interesting recommendation - very much in line with this paper from a few weeks ago: https://pubmed.ncbi.nlm.nih.gov/40878356/
TLDR: women who would otherwise be missed by current algorithms might be picked up by this inflammatory marker (hs-CRP)
I suspect Lp(a) is next, since there are now drugs in clinical trials that directly lower it.
It’s important to put this in context.
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
What about GLP-1 antagonists to lower inflammation / hs-CRP?
So does this mean apoB or hs-CRP is a better predictor of heart disease?
Cholesterol and statins have always been suspect science in any case:
https://medium.com/@petilon/cholesterol-and-statins-e7d9d8ee...
From https://www.cochrane.org/evidence/CD004816_statins-primary-p...:
> 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.
You should actually read the article. In particular:
> 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.
Careful. You are correct at what we want for primary prevent. However for primary prevention we need much larger sample sizes and thus data is much harder to get.
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.
> Lack of data doesn't mean the treatment won't work
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!
And after 2013 in the BMJ on statins:
https://www.bmj.com/campaign/statins-open-data
It’s not that lowering cholesterol does not decrease heart disease, but the fundamental problem of heart disease is not cholesterol, it’s the inflammation.
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.
Why do we see lower mortality in mendelian randomisation studies for individuals with SNPs that code for lower cholesterol, then?
For the last time. I am not saying that lowering cholesterol does not lower the risk of CVD. I am saying that it is oxidized cholesterol that causes CVD, and by lowering cholesterol you are also lowering oxidized cholesterol. Cholersterol good. oxidized cholesterol bad.
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.
Where we agree is that oxidation of LDL is part of the atherogenesis pathway.
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.
MR studies rule out the idea that inflammation is the sole causal factor, and we have a lot of them.
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.
https://pubmed.ncbi.nlm.nih.gov/25770315/
https://www.nejm.org/doi/full/10.1056/NEJMoa1604304
Published 2013
The human body evolves on a much slower time scale than decades
Piles of money at stake, misinterpreting data, cherry picking data, misplaced pride leading to hiding data or worse, etc...
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.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4836695/
Your argument I responded to wasn't that the consensus of science is wrong, your argument was that the study is not valid because it was from the early 2010s
This is not a mainstream view of the science, and it's worth noting that this perspective is also not supported by the OP or by the JACC article that it's citing.
It's true that most doctors and pharmaceutical companies maintain that statins are effective. But there are plenty of statistically educated people that don't think they have much of an effect on all-cause mortality.
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.
And my understanding of the science is that statins reduce inflammation.
> This is not a mainstream view of the science, and it's worth noting that this perspective is also not supported by the OP or by the JACC article that it's citing.
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.
The view among "authorities" is certainly something I find relevant in assessing a highly opinionated but thinly sourced medium article from someone who, respectfully, I've never heard of and know nothing about. Certainly it would be defeasible by a closer look at the research itself. But, barring that, it's a very useful heuristic.
I'm not suggesting you should take the medium article at face value either. Just that if you don't know enough to evaluate the evidence, you don't know enough to dismiss any particular opinion.
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.
appeals to authority have some merit, you know.
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.
> appeals to authority have some merit, you know.
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.
yes they do. for one thing you do not make the rules around here; no one cares what you think counts as suitable grounds for arguing. For another, yes, authority has some merit. Doesn't make it fact, but certainly the prior we ought to assign for "medical authorities are correct" is quite high. Not certainty, but pretty confident, all else being equal.
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.
> for one thing you do not make the rules around here; no one cares what you think counts as suitable grounds for arguing.
You're asserting that a extremely well-known logical fallacy is not a fallacy. It's not an HN rule, it's argumentation 101.
> You're asserting that a extremely well-known logical fallacy is not a fallacy.
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.
Experts can be wrong, even in mass consensus.
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.
as others have noted, you seem to be unaware of what exactly the fallacy refers to. You might want to look it up. It is not "citing an authority at all" but rather "citing an authority's opinion as though it were logical fact". Which nobody is doing here.
You started this subthread by saying:
> 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.
No... I called it disingenuous. I didn't use the word lie because that's not what I meant. The inference 'disingenuous = lie' is false.
https://www.merriam-webster.com/dictionary/disingenuous
Lacking in candor.
also : giving a false appearance of simple frankness : calculating
... What is going on? Yes, that's what it means, that's why I used it. Notice it does not say 'lie' or anything directly synonymous with lying. It's related, sure, but not the same.
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 is no logical fallacy in play here. Nobody is saying “the argument is wrong because of who said it”. 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: because the consensus is usually right.
> There is no logical fallacy in play here. Nobody is saying “the argument is wrong because of who said it”.
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.
More than just an assertion: the consensus is that the consensus is usually right, you see.
Well yes, exactly: it's just consensuses all the way down. Which is just another way of saying "I feel like it's right and you're wrong, even though I have no actual evidence either way."
You are confusing what "Appeal to Authority" fallacy is. Namely you are ignoring the fallaciousness of it.
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.
But statins are incredibly good at reducing inflammation anyway.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5633715/
The Medium blog you linked has 9 citations and none of them are actual scientific research. They're all news articles.
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.
> They're all news articles.
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.
Any cardiologist will tell you statins have saved millions of lives. And that they also have side effects that make them not an option for a significant chunk of the population.
Statins are not evil and they're not a scam, but we definitely need to replace them with something better.
Sure statins may have saved lives, but the question is how. Is it by controlling LDL, or by reducing inflammation? This story says it is the latter: https://www.bloomberg.com/news/articles/2008-04-15/heart-dis...
Most of this is reputation is based on early generation statins. The side effect profile is incredibly slimmed down on statins like rosuvastatin.
What a boatload of crap.
> 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.
I'm unaware of any evidence for ppcsk9 inhibitors outside of the same cohorts (people with existing CVD) that the OP is citing.
Do you have any?
What about Vytorin trial?
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
Not really, the evidence that ldl causes heart disease and statins prevent deaths is very, very, very strong (lots of clinical trials, lots of causal evidence e.g. Mendelian randomization). LDL is extremely harmful!
So you are saying the human body manufactures a substance that is extremely harmful to the body. And yet lowering it artificially can lead to issues such as loss of short term memory. The body needs cholesterol! You could qualify your argument by saying that excess LDL is harmful.
The body needs SOME. Evolution doesn't care about when you die, just that you reproduce first. Even the highest cholesterol cases generally have kids old enough to have their own kids before they die. That is enough for evolution to not care.
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.
The body can produce needed cholesterol locally just fine. The PCKS9 inhibitor trials show that having basically no serum LDL is not harmful. People that have the genetic mutation that results in no PCKS9 have extremely low rates of CVD
> You could qualify your argument by saying that excess LDL is harmful.
It’s so obvious it doesn’t need to be stated dude.
That's a hot take of a blog post.
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 cholesterol to heart disease link is one of the best attested in medical science
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.
Other methods do.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6661243/
It's a bad blog post for sure. However, I've a few smart people say that lower cholesterol may not be what makes statins powerful: it's the anti-inflammatory properties. I'm too lazy to find papers right now.
Yes, there is certaintly data to make that argument. The argument that inflammation is a better predictor of heart disease than cholesterol is a reasonable one. On the other hand the argument that cholesterol is not a good predictor of heart disease and cholesterol lowering therapy is a fraud is not reasonable in the face of the evidence.
> It's a bad blog post for sure
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 can't be bad unless the original sources it cites 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.
Age-standardized cardiovascular mortality dropped steadily from 1975 to 2010 (with no particular discontinuity when statins were introduced), and has not budged since 2010.
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.
> Age-standardized cardiovascular mortality dropped steadily from 1975 to 2010 (with no particular discontinuity when statins were introduced), and has not budged since 2010.
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.
[dead]
Single author
Unknown editor
No journal? Committee? Conference?
Ew.
https://www.jacc.org/doi/10.1016/j.jacc.2025.08.047
Thanks!! I completely missed that.
The post links to the JACC article (which is an American College of Cardiology consensus statement).
Yep yep, just saw that, thanks <3
How do you measure inflammation !
hs-CRP levels from a blood test.
> The ACC is now recommending that everyone measure inflammation (specifically, hs-CRP)
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.
Do you have a link to an article that covers the history? In the time that I've been following this topic (about 10 years), hs-CRP has been the go-to biomarker of inflammation. It'd be interesting to learn about the process required to get there.
CRP and its subtypes have been known since 1930 as markers of acute inflammation such as following disease or injury. The measurement of chronic systemic inflammation is more difficult, because it involves lower levels of the biomarkers. So for example CRP levels increase by a factor of thousands when there is an infection, but in chronic systemic inflammation are elevated much more subtly. I don't know a great historical review but this "Nature Perspective" from 2019 seems pretty good:
https://zellavie.ch/wp-content/uploads/2020/06/Nature-Medici...
Oh yes I agree with you. This seems important.
This is now a thing because of the covid vax no less
For decades, LDL cholesterol has been the main target in preventive heart health.
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).
Thanks for the summary! I haven’t read tfa yet, so my apologies if this is answered in there, but: does this mean that we’ve already reduced the contribution from cholesterol to events? Or that cholesterol was simply associated and not causative? I imagine the truth is somewhere in between, perhaps we can guess that’s it’s 70% due to one and 30% due to the other?
It's more the former -- we've gotten so good at detecting high cholesterol and reducing it, that the majority of residual risk is now in the other factors.
(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.)
1. Thanks for the reply!
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.
I'm interested in this subject. Can you cite some of the RCTs and mechanistic evidence?
Does this mean this test is recommenced in place of cholesterol for people who are not taking statins? Or is the test in addition?
Recommended in addition to cholesterol (or better yet, ApoB). And recommended for everyone, not just those taking statins.
Interesting, thanks. I'm changing docs/insurance and thinking about the tests I should be paying attention to.
Is this...a summary? The wording is so close to the article in parts that I'm not sure.
This is a summary -- I'm the article author and the author of that comment, so I would hope my wording is consistent. :)
Oh, missed the username. Normally when people post a comment like that they prepend it with something like "Author here, just wanted to add X/Y/Z"
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.
Green highlight is for new users.
Oh. They should add a highlight for comments written by the poster as well. Or some kind of [poster] tag, not sure. Would be useful in these cases.
Fair point!
[dead]
This is clearly now a thing due to the covid "vaccine" myocarditis, pericarditis