This paper's core idea is based on the assumption that circulating LDL is the cause of heart disease. That assumption is false.
Taking satins is proven to reduce heart disease rates, but there are lots of other drugs that lower LDL... many with much more efficacy than satins.
These non-satin drugs do not reduce heart disease rates significantly.
There something else going on here. High LDL is correlated with the development of heart disease, but it does not cause heart disease. Satins do reduce the risk of heart disease and they do reduce LDL, but their positive effect on heart disease rates is not caused by reduced LDL.
There are multiple independent risk factors for heart disease. The major ones are:
- LDL / ApoB
- Blood pressure
- inflammation (hs-CRP)
- Insulin resistance (HbA1c)
- Lp(a): strongest hereditary risk factor.
- eGFR: a measure of kidney function
Non-statin drugs like PCSK9 inhibitors have been shown to reduce heart attacks, strokes, and other cardiovascular events on top of statin therapy. One randomized control trial was FOURIER in 2017: https://www.nejm.org/doi/full/10.1056/NEJMoa1615664
Think of heart disease as slow, long-term damage to the cardiovascular system, and cholesterol is what the body uses as a bandaid.
If you have a lot of LDL cholesterol available, your body will use a lot of it, and you'll have stiffer arteries. If you don't have much available, it takes longer for the bandaids to build up.
This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality.
I think there's a a bit of a paradox here: cardiovascular disease is solved biomedically, yet still remains the #1 cause of death worldwide.
From a biomedical standpoint, we have highly accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, knowledge of nutritional biochemstry, and next generation drugs like PCSK9 inhibitors and lepodisiran that can lower ApoB and Lp(a) by 90%. So there's no fundamental reason why cardiovascular disease has to be in even the top 10 causes of death.
Practically speaking, providing guideline-recommended preventive care would require ~27 hours per doctor per day. And the incentives are misaligned: health systems profit when hospital beds are full, so they lack the business model to actually invest in prevention.
So it's a clear illustration of a systematic gap between research and care delivery.
Thanks for sharing this and empowering others to improve their heart health outcomes.
I’m not in love with the idea of sharing my biomarkers with multiple health-tech companies and really want a self-hosted solution to import biomarkers from multiple sources such as Apple Health, arbitrary csv and jsons while avoiding duplication.
Claude Code is something that will make this dream a reality for me pretty soon.
Do you have any tips on biomarker data design or import gotchas?
Well, and everyone knows they should exercise, and many know they should avoid dietary saturated fats, but most people neither exercise nor avoid highly fatty foods.
the mainline guideline is more exercise and better diet which is the treatment to much more than just heart disease. that's not something 27 hours of doctors a day can provide unless you give them guns
the treatments reduce risk, but they don't change the fact the human body is very reliant on the heart and increasingly vulnerable to cardiac death with age, even with perfect biomarkers
given the entrenched attitudes and the time it takes to actually get people to do the thing as evidenced by all the contrarians in the thread...
it would take a lot more than that. Ain't no doc got all that time to go through all this with every person who should take cholesterol lowering medicine but wants to argue their internet sourced bs
“Solved problem” is too strong of language, but the cardiologists I follow are generally open about the idea that we have enough tools and knowledges to reasonably prevent and manage it the average person.
Even without medications, we’ve had enough knowledge about diet and lifestyle factors that the average person (excluding generic abnormalities that lead to abnormally high risk) could reasonably avoid heart disease through lifestyle and diet alone. That’s easier said than done for a lot of people in the modern world, so it’s good that we have a few different medications on top of that knowledge.
It's almost entirely a lifestyle problem. Shit diet, lack of exercise, obesity, &c. Overlap maps of obesity and cardiovascular deaths, they're virtually the same
Ages ago, I used to do the typesetting for the _Cardiosource Review Journal_ (lived my life around the publishing schedule because no one else was able to run a WordBASIC macro to do initial formatting, import that into a page layout program, process all the graphics and place them, and generate page proofs early enough that it could be proofed and corrected with a 24hr. turn-around until a postal rate increase killed it) --- cardiologists seem very big on data/analysis, moreso than most other medical fields.
My cardiologist recently told me the disease is mostly from Lipo(a) and small dense Ldl, that it took decades from being able to measure LDL and note the correlation to disease to be able to measure there more specific factors, and even more time to nail down the observations.
Lipo(a) is genetic, apparently either you have it or not.
Small dense ldl is caused apparently (not a biologist) from high triglycerides, one cause of which is high sugar diet.
I think the title is deliberately provocative, but they're not wrong.
Heart disease is largely solvable from a biomedical standpoint: we have accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, precision nutrition, and highly effective next-generation drugs (PCSK9 inhibitors, lepodisiran, etc).
But practically speaking, heart disease remains the #1 cause of death due to bottlenecks in care delivery: e.g., 46% U.S. counties have no cardiologists, providing guideline-recommended preventive care would require ~27 hours per doctor per day, and incentives are misaligned (health systems profit when hospital beds are full, not from prevention).
It is very much not a solved problem unless you can actually cure it in existing patients, e.g. reduce or remove the extant plaques from their blood vessels.
This is not pedantry, this is a vital problem of hundreds of millions of currently living people, many of which don't even know their own status.
I believe this can be done in the near future, there are some interesting initiatives in this direction, but it is very much not a solved problem.
I agree with you, but I suppose the point of the article is that we can solve cardiovascular disease without first solving obesity or chronic inactivity.
I wish the “counter points” to my claims were always as bad as that link. It has a little bit of everything, from Fauci to seed oils to a Joe Rogan video.
Here is the chief editor of JAMA internal medicine arguing there is not enough evidence to prescribe statins for primary prevention in those 40+: https://www.natap.org/2016/HIV/ied160021.pdf
Thanks for sharing this — amazing resource and resembles my experience with US health care.
I recently asked my doctor at Stanford - a pretty expensive hospital but one of the top cardio hospitals in the country - to get me an APoB test. He said that it may not be covered by insurance.
So instead I spend $360 or so on a year worth of biomarkers from Function Health that included ApoB and others
>Lp(a) levels are almost purely genetically determined and so elevated Lp(a) is essentially due to a poor roll of the genetic dice... For simplicity, we will devote little further attention to either of these secondary risk factors”
As someone who rolled poorly on those genetic dice, I would like to complain. But also, disregarding a factor that impacts 20%[1] of the population seems disingenuous.
Layering PCSK9 inhibitors, ezetimibe, and statins can lower ApoB/LDL cholesterol by 85–90%, which would have been unheard of until recently.
On the horizon, drugs in clinical trials lower Lp(a) (the strongest hereditary risk factor for heart disease) by 94%. Currently, there are four RNA-based drugs in trials that effectively silence the gene that makes Lp(a) in liver cells: lepodisiran, olpasiran, pelacarsen, and zerlasiran.
If you’re unlucky enough to have one of the genetic factors that predisposes you to atherosclerosis then it’s going to be statins and maybe PCSK9 inhibitors.
For the average person, diet and lifestyle choices could be enough, but adherence can be difficult. Monitoring LDL as an imperfect but useful marker and then introducing low-dose statins on a sliding scale proportions to severity is a good idea.
Statins are not completely side effect free (no medication really is) but they’re generally well tolerated. Statin side effects are an interesting area of research because they have a very high nocebo effect rate: People hear so much about statins and their side effects from popular media that when they’re prescribed a statin in older age they start thinking everything is a side effect of the statin. There are some actual known side effects of statins which scale with dose and some of which can be maybe offset by supplements like CoQ10, but the side effects are generally mild. I’d take the side effects over heart disease after watching some older family members struggle and then die due to heart problems.
My experience with them was a brain fog so bad I could hardly do my engineering job effectively. Quite unfortunate as I've read that side effect isn't very common.
This paper's core idea is based on the assumption that circulating LDL is the cause of heart disease. That assumption is false.
Taking satins is proven to reduce heart disease rates, but there are lots of other drugs that lower LDL... many with much more efficacy than satins.
These non-satin drugs do not reduce heart disease rates significantly.
There something else going on here. High LDL is correlated with the development of heart disease, but it does not cause heart disease. Satins do reduce the risk of heart disease and they do reduce LDL, but their positive effect on heart disease rates is not caused by reduced LDL.
There are multiple independent risk factors for heart disease. The major ones are:
Non-statin drugs like PCSK9 inhibitors have been shown to reduce heart attacks, strokes, and other cardiovascular events on top of statin therapy. One randomized control trial was FOURIER in 2017: https://www.nejm.org/doi/full/10.1056/NEJMoa1615664Why do we see consistent dose response between LDL lowering SNPs and cardiovascular disease in Mendelian randomisation studies, then?
Heart disease is clearly not Mendelian. So, unless you have a specific well-designed study to cite, that is a non-argument.
> [that circulating LDL is the cause of heart disease] is false.
I think your comment really owes the rest of us more explanation of this part.
*statins?
The fact that this word is misspelt every single time makes me want to dismiss the entirety of the comment.
Simplifying, we are all essentially born with heart disease. It's just a game of how long it takes for it to kill us. No way around it.
Unfortunately, our biology isn't perfect.
That’s not really a helpful attitude to take when trying to prevent heat disease though
The article goes on to say it's not all LDL. Keep reading. The first part agrees with my cardiologist, at any rate
> High LDL is correlated with the development of heart disease, but it does not cause heart disease.
You realize this sentence is an oxymoron?
Unless you meant to say "it does not cause the development of heart disease". I agree correlation is not causation.
I don't think it is. Something can either be correlated and causal or correlated and non-causal. It makes sense to talk about which.
> You realize this sentence is an oxymoron?
No it isn't.
Think of heart disease as slow, long-term damage to the cardiovascular system, and cholesterol is what the body uses as a bandaid.
If you have a lot of LDL cholesterol available, your body will use a lot of it, and you'll have stiffer arteries. If you don't have much available, it takes longer for the bandaids to build up.
This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality.
You realize correlation does not imply causation?
Edit: this was written before OP edited their comment
I wonder how many Cardiologists would call cardiovascular disease “a solved problem”
My bet is close to none
I think there's a a bit of a paradox here: cardiovascular disease is solved biomedically, yet still remains the #1 cause of death worldwide.
From a biomedical standpoint, we have highly accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, knowledge of nutritional biochemstry, and next generation drugs like PCSK9 inhibitors and lepodisiran that can lower ApoB and Lp(a) by 90%. So there's no fundamental reason why cardiovascular disease has to be in even the top 10 causes of death.
Practically speaking, providing guideline-recommended preventive care would require ~27 hours per doctor per day. And the incentives are misaligned: health systems profit when hospital beds are full, so they lack the business model to actually invest in prevention.
So it's a clear illustration of a systematic gap between research and care delivery.
> I think there's a a bit of a paradox here: cardiovascular disease is solved biomedically, yet still remains the #1 cause of death worldwide.
Because most people don't give a shit about their health, no amount of pills will save you if you eat like the average american.
Thanks for sharing this and empowering others to improve their heart health outcomes.
I’m not in love with the idea of sharing my biomarkers with multiple health-tech companies and really want a self-hosted solution to import biomarkers from multiple sources such as Apple Health, arbitrary csv and jsons while avoiding duplication.
Claude Code is something that will make this dream a reality for me pretty soon.
Do you have any tips on biomarker data design or import gotchas?
Well, and everyone knows they should exercise, and many know they should avoid dietary saturated fats, but most people neither exercise nor avoid highly fatty foods.
Couple of reasons why I think this is nonsense .
the mainline guideline is more exercise and better diet which is the treatment to much more than just heart disease. that's not something 27 hours of doctors a day can provide unless you give them guns
the treatments reduce risk, but they don't change the fact the human body is very reliant on the heart and increasingly vulnerable to cardiac death with age, even with perfect biomarkers
given the entrenched attitudes and the time it takes to actually get people to do the thing as evidenced by all the contrarians in the thread...
it would take a lot more than that. Ain't no doc got all that time to go through all this with every person who should take cholesterol lowering medicine but wants to argue their internet sourced bs
“Solved problem” is too strong of language, but the cardiologists I follow are generally open about the idea that we have enough tools and knowledges to reasonably prevent and manage it the average person.
Even without medications, we’ve had enough knowledge about diet and lifestyle factors that the average person (excluding generic abnormalities that lead to abnormally high risk) could reasonably avoid heart disease through lifestyle and diet alone. That’s easier said than done for a lot of people in the modern world, so it’s good that we have a few different medications on top of that knowledge.
the cardiologist I pay, visit and follow, would likely advise perfect diet and excercise will only reduce risk not eliminate it.
So it comes down to definition of 'resaonably'. diet and excercise will 'reasonably' reduce risk of most disease.
It's almost entirely a lifestyle problem. Shit diet, lack of exercise, obesity, &c. Overlap maps of obesity and cardiovascular deaths, they're virtually the same
https://ec.europa.eu/eurostat/documents/4187653/10321616/dea...
https://ec.europa.eu/eurostat/statistics-explained/images/th...
Ages ago, I used to do the typesetting for the _Cardiosource Review Journal_ (lived my life around the publishing schedule because no one else was able to run a WordBASIC macro to do initial formatting, import that into a page layout program, process all the graphics and place them, and generate page proofs early enough that it could be proofed and corrected with a 24hr. turn-around until a postal rate increase killed it) --- cardiologists seem very big on data/analysis, moreso than most other medical fields.
following a few cardiology conference i tend to agree with you, far from this sadly
Ask yourself what happens to them if it’s solved.
I mean their livelihood is predicated on it not being solved for a portion of the population
Some information on the author:
- The blog seems to be associated with this Twitter account: https://x.com/sichuan_mala. That person seems to be a good friend of Cremieux¹.
- The article seems to have originally been published/unpublished in 2024 https://x.com/cremieuxrecueil/status/1922743591924899962
- It was only re-uploaded in September 2025 (?). There's some discussion of the claims under a tweet by Cremieux who announced the re-upload: https://x.com/cremieuxrecueil/status/1974990143544287715
¹) FWIW: https://en.wikipedia.org/wiki/Jordan_Lasker
archive just in case https://archive.ph/Od1VS
anybody in the medical field able to give some report on state of the art CV research ?
My cardiologist recently told me the disease is mostly from Lipo(a) and small dense Ldl, that it took decades from being able to measure LDL and note the correlation to disease to be able to measure there more specific factors, and even more time to nail down the observations.
Lipo(a) is genetic, apparently either you have it or not.
Small dense ldl is caused apparently (not a biologist) from high triglycerides, one cause of which is high sugar diet.
I think the title is deliberately provocative, but they're not wrong.
Heart disease is largely solvable from a biomedical standpoint: we have accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, precision nutrition, and highly effective next-generation drugs (PCSK9 inhibitors, lepodisiran, etc).
But practically speaking, heart disease remains the #1 cause of death due to bottlenecks in care delivery: e.g., 46% U.S. counties have no cardiologists, providing guideline-recommended preventive care would require ~27 hours per doctor per day, and incentives are misaligned (health systems profit when hospital beds are full, not from prevention).
It is very much not a solved problem unless you can actually cure it in existing patients, e.g. reduce or remove the extant plaques from their blood vessels.
This is not pedantry, this is a vital problem of hundreds of millions of currently living people, many of which don't even know their own status.
I believe this can be done in the near future, there are some interesting initiatives in this direction, but it is very much not a solved problem.
Obesity, junk food addiction, and chronic inactivity still remain unsolved as ever.
I agree with you, but I suppose the point of the article is that we can solve cardiovascular disease without first solving obesity or chronic inactivity.
Obesity is solved! Tirzepatide.
GLP-1's baby.
Here’s a counterpoint if anyone is interested: https://www.midwesterndoctor.com/p/why-are-statins-so-danger...
I’m not saying either side is right but when it comes to your health why not evaluate as many opinions as possible.
I wish the “counter points” to my claims were always as bad as that link. It has a little bit of everything, from Fauci to seed oils to a Joe Rogan video.
Here is the chief editor of JAMA internal medicine arguing there is not enough evidence to prescribe statins for primary prevention in those 40+: https://www.natap.org/2016/HIV/ied160021.pdf
Your article starts by comparing the harms of statins to the harms of scary COVID vaccines. I'm not sure it's very credible.
Commenters are really piling on, without, it seems, reading the article.
The author addresses a lot of the obvious gotcha points I see in the comments.
Although I don't think the author realistically explores the downsides of statin use, papering over the common side-effects.
Dramatic clickbait titles should expect to get responses that match.
Very similar to https://myticker.com/ though a little denser.
Thanks for sharing this — amazing resource and resembles my experience with US health care.
I recently asked my doctor at Stanford - a pretty expensive hospital but one of the top cardio hospitals in the country - to get me an APoB test. He said that it may not be covered by insurance.
So instead I spend $360 or so on a year worth of biomarkers from Function Health that included ApoB and others
It was my understanding that circulating free triglycerides and LpA were the main risk factors for CAD and not LDL. In addition to AGEs?
>Lp(a) levels are almost purely genetically determined and so elevated Lp(a) is essentially due to a poor roll of the genetic dice... For simplicity, we will devote little further attention to either of these secondary risk factors”
As someone who rolled poorly on those genetic dice, I would like to complain. But also, disregarding a factor that impacts 20%[1] of the population seems disingenuous.
[1] - https://familyheart.org/family-sharing-tools/high-lpa-family...
Lepodisiran has reduced Lp(a) by 94% in clinical trails. After it gets approved, IMO the author should re-write this section.
Valve failure often has nothing to do with diet. This is junk.
There are other cardiac failure modes too, for example electrical and hypertrophy.
Why was this flagged? I was under the impression that the content of the article reflects the current mainstream medical view.
Hm, so statins for everyone? What’re the downsides?
The main side effects of statins are muscle pain and brain fog (from some statins -- others cross the blood-brain barrier much less).
The benefit of statins is to not only lower LDL cholesterol, but also inflammation, which is now actually a stronger risk factor for cardiovascular disease than cholesterol: https://www.empirical.health/blog/inflammation-and-heart-hea...
Layering PCSK9 inhibitors, ezetimibe, and statins can lower ApoB/LDL cholesterol by 85–90%, which would have been unheard of until recently.
On the horizon, drugs in clinical trials lower Lp(a) (the strongest hereditary risk factor for heart disease) by 94%. Currently, there are four RNA-based drugs in trials that effectively silence the gene that makes Lp(a) in liver cells: lepodisiran, olpasiran, pelacarsen, and zerlasiran.
I’m old enough that my parents/spouse’s parents are all on statins. They all report side-effects, mostly digestive issues.
I’ll eat a healthy diet, exercise, and live a life without persistent diarrhea. I’ll take statins if/when they are medically necessary, and no sooner.
If you’re unlucky enough to have one of the genetic factors that predisposes you to atherosclerosis then it’s going to be statins and maybe PCSK9 inhibitors.
For the average person, diet and lifestyle choices could be enough, but adherence can be difficult. Monitoring LDL as an imperfect but useful marker and then introducing low-dose statins on a sliding scale proportions to severity is a good idea.
Statins are not completely side effect free (no medication really is) but they’re generally well tolerated. Statin side effects are an interesting area of research because they have a very high nocebo effect rate: People hear so much about statins and their side effects from popular media that when they’re prescribed a statin in older age they start thinking everything is a side effect of the statin. There are some actual known side effects of statins which scale with dose and some of which can be maybe offset by supplements like CoQ10, but the side effects are generally mild. I’d take the side effects over heart disease after watching some older family members struggle and then die due to heart problems.
Possible side effects include muscle damage, liver damage, and type 2 diabetes.
My experience with them was a brain fog so bad I could hardly do my engineering job effectively. Quite unfortunate as I've read that side effect isn't very common.
Well, that's certainly a ... hypothesis.
And an N of 1 "experiment" on whoever wrote this.
"Hunger is a solved problem. We just need to give enough food to everyone!"
This is dangerous nonsense and should be removed from the HN front page.
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