6 ms·

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 red

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.

thomassmith65 9mo ago
*statins?
- blell 9mo ago
  The fact that this word is misspelt every single time makes me want to dismiss the entirety of the comment.
  - mark-r 9mo ago
    My browser underlines the word statin to indicate a misspelling, but does not underline satin. We've been trained to believe the computer is always right when it flags an error, but unfortunately it's not 100% accurate.
medstrom 9mo ago
> 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.
- elromulous 9mo ago
  You realize correlation does not imply causation? Edit: this was written before OP edited their comment
- rowanG077 9mo ago
  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.
- smt88 9mo ago
  > 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.
  - KempyKolibri 9mo ago
    The band aid analogy doesn’t make sense when we consider the MR studies showing the lower your genetically determined LDL-c, the lower your risk of CVD. If everything was randomised except the number of band aids, why would having fewer band aids result in lower CVD risk? > This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality. That’s one potential explanation, but I don’t think it’s the most likely one. We tend to see non significant ACM in smaller, less powered trials, or those with lower LDL-c lowering. ACM is simply a less sensitive endpoint - if you have a treatment that reduces CVD incidence, then the “CVD incidence” endpoint will give you significant results with fewer CVD event differences between study arms compared to ACM since your power to detect differences is diluted by other fatal events that aren’t affected by statins (cancer, motor accidents etc).
KempyKolibri 9mo ago
Why do we see consistent dose response between LDL lowering SNPs and cardiovascular disease in Mendelian randomisation studies, then?
- daveguy 9mo ago
  Heart disease is clearly not Mendelian. So, unless you have a specific well-designed study to cite, that is a non-argument.
  - graboy 9mo ago
    https://www.jacc.org/doi/10.1016/j.jacc.2012.09.017 https://www.jacc.org/doi/10.1016/j.jacc.2012.09.017 Across different genetic variants, lower lifetime LDL -> lower risk of death. Check out figure 3. The causality of LDL -> plaque buildup -> 55-60% [1] of heart disease related deaths is also well understood, so it seems clear to me that preventing plaque buildup in the first place prevents over half of heart disease related deaths. Would like to know if you disagree, "Minimize LDL at all costs" goes current mainstream medical guidance, so I'd like to disconfirm my beliefs if possible. [1] Number from deep research.
  - KempyKolibri 9mo ago
    Graboy has provided the citation I would have given, as well as an excellent explanation. I’m not sure what you mean by “heart disease is clearly not Mendelian”.
    - daveguy 9mo ago
      Mendelian is characterized by effects having strong influence from a single gene. Heart disease is clearly more complex than gene -> heart disease. I thought that was basic enough that I didn't need to explain it. But here goes... A clinical score changing with treatment is not unconfounded by mendelian randomization. When the genetics are clearly more complex than what you are mathematically randomizing for, the control doesn't solve the confounding. eg you haven't suddenly "proven" the effects are non-genetic. We already knew heart disease is non-mendelian. But showing something is non-mendelian doesn't mean you've shown it's not genetic. I hope that clarifies, because I'm not sure I can explain it to you in simpler terms.
brandonb 9mo ago
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 https://www.nejm.org/doi/full/10.1056/NEJMoa1615664
justinator 9mo ago
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.
- mock-possum 9mo ago
  That’s not really a helpful attitude to take when trying to prevent heat disease though
  - justinator 9mo ago
    Reality is like that. Before hoping for a miracle, may I suggest adding more walks into your week?
loeg 9mo ago
> [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.
readthenotes1 9mo ago
The article goes on to say it's not all LDL. Keep reading. The first part agrees with my cardiologist, at any rate

thomassmith65 9mo ago

*statins?

blell 9mo ago
The fact that this word is misspelt every single time makes me want to dismiss the entirety of the comment.
- mark-r 9mo ago
  My browser underlines the word statin to indicate a misspelling, but does not underline satin. We've been trained to believe the computer is always right when it flags an error, but unfortunately it's not 100% accurate.

medstrom 9mo ago

> 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.

elromulous 9mo ago
You realize correlation does not imply causation? Edit: this was written before OP edited their comment
rowanG077 9mo ago
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.
smt88 9mo ago
> 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.
- KempyKolibri 9mo ago
  The band aid analogy doesn’t make sense when we consider the MR studies showing the lower your genetically determined LDL-c, the lower your risk of CVD. If everything was randomised except the number of band aids, why would having fewer band aids result in lower CVD risk? > This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality. That’s one potential explanation, but I don’t think it’s the most likely one. We tend to see non significant ACM in smaller, less powered trials, or those with lower LDL-c lowering. ACM is simply a less sensitive endpoint - if you have a treatment that reduces CVD incidence, then the “CVD incidence” endpoint will give you significant results with fewer CVD event differences between study arms compared to ACM since your power to detect differences is diluted by other fatal events that aren’t affected by statins (cancer, motor accidents etc).

KempyKolibri 9mo ago

Why do we see consistent dose response between LDL lowering SNPs and cardiovascular disease in Mendelian randomisation studies, then?

daveguy 9mo ago
Heart disease is clearly not Mendelian. So, unless you have a specific well-designed study to cite, that is a non-argument.
- graboy 9mo ago
  https://www.jacc.org/doi/10.1016/j.jacc.2012.09.017 https://www.jacc.org/doi/10.1016/j.jacc.2012.09.017 Across different genetic variants, lower lifetime LDL -> lower risk of death. Check out figure 3. The causality of LDL -> plaque buildup -> 55-60% [1] of heart disease related deaths is also well understood, so it seems clear to me that preventing plaque buildup in the first place prevents over half of heart disease related deaths. Would like to know if you disagree, "Minimize LDL at all costs" goes current mainstream medical guidance, so I'd like to disconfirm my beliefs if possible. [1] Number from deep research.
- KempyKolibri 9mo ago
  Graboy has provided the citation I would have given, as well as an excellent explanation. I’m not sure what you mean by “heart disease is clearly not Mendelian”.
  - daveguy 9mo ago
    Mendelian is characterized by effects having strong influence from a single gene. Heart disease is clearly more complex than gene -> heart disease. I thought that was basic enough that I didn't need to explain it. But here goes... A clinical score changing with treatment is not unconfounded by mendelian randomization. When the genetics are clearly more complex than what you are mathematically randomizing for, the control doesn't solve the confounding. eg you haven't suddenly "proven" the effects are non-genetic. We already knew heart disease is non-mendelian. But showing something is non-mendelian doesn't mean you've shown it's not genetic. I hope that clarifies, because I'm not sure I can explain it to you in simpler terms.

brandonb 9mo ago

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 https://www.nejm.org/doi/full/10.1056/NEJMoa1615664

justinator 9mo ago

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.

mock-possum 9mo ago
That’s not really a helpful attitude to take when trying to prevent heat disease though
- justinator 9mo ago
  Reality is like that. Before hoping for a miracle, may I suggest adding more walks into your week?

loeg 9mo ago

> [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.

readthenotes1 9mo ago

The article goes on to say it's not all LDL. Keep reading. The first part agrees with my cardiologist, at any rate