7 ms·

Cholesterol and statins have always been suspect science in any case: https://medium.com/@petilon/cholesterol-and-statins-e7d9d8eea983 https://medium.com/@peti

Cholesterol and statins have always been suspect science in any case: https://medium.com/@petilon/cholesterol-and-statins-e7d9d8eea983 https://medium.com/@petilon/cholesterol-and-statins-e7d9d8ee...

bkandel 1y ago
From https://www.cochrane.org/evidence/CD004816_statins-primary-prevention-cardiovascular-disease 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.
- guerby 1y ago
  Published 2013
  - malfist 1y ago
    The human body evolves on a much slower time scale than decades
    - guerby 1y ago
      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 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/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4836695/
      - malfist 1y ago
        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
- FollowingTheDao 1y ago
  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.
  - KempyKolibri 1y ago
    Why do we see lower mortality in mendelian randomisation studies for individuals with SNPs that code for lower cholesterol, then?
    - FollowingTheDao 1y ago
      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/articles/10.3389/fcvm.2022.1023651/full 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.
      - cthalupa 1y ago
        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%3D10.1371/journal.pmed.1003062 https://journals.plos.org/plosmedicine/article%3Fid%3D10.137... https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00086-6/fulltext 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.bmj.com/content/342/bmj.d548 https://www.ahajournals.org/doi/10.1161/01.atv.0000258869.48076.14 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 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://pubmed.ncbi.nlm.nih.gov/25770315/ https://www.nejm.org/doi/full/10.1056/NEJMoa1604304 https://www.nejm.org/doi/full/10.1056/NEJMoa1604304
- guerby 1y ago
  And after 2013 in the BMJ on statins: https://www.bmj.com/campaign/statins-open-data https://www.bmj.com/campaign/statins-open-data
- timr 1y ago
  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.
  - bluGill 1y ago
    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.
    - timr 1y ago
      > 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!
carbocation 1y ago
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.
- e40 1y ago
  And my understanding of the science is that statins reduce inflammation.
- timr 1y ago
  > 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.
  - ajkjk 1y ago
    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.
    - timr 1y ago
      > 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.
Calavar 1y ago
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/192160 https://jamanetwork.com/journals/jama/article-abstract/19216... [2] https://pubmed.ncbi.nlm.nih.gov/25815993/ https://pubmed.ncbi.nlm.nih.gov/25815993/ [3] https://jamanetwork.com/journals/jamacardiology/article-abstract/2537381 https://jamanetwork.com/journals/jamacardiology/article-abst... [4] https://www.ahajournals.org/doi/abs/10.1161/01.CIR.67.4.730 https://www.ahajournals.org/doi/abs/10.1161/01.CIR.67.4.730 [5] https://jamanetwork.com/journals/jama/fullarticle/2678614 https://jamanetwork.com/journals/jama/fullarticle/2678614 [6] https://pubmed.ncbi.nlm.nih.gov/32507339/ https://pubmed.ncbi.nlm.nih.gov/32507339/ [7] https://www.tandfonline.com/doi/abs/10.1080/07315724.2008.10719668 https://www.tandfonline.com/doi/abs/10.1080/07315724.2008.10... [8] https://pubmed.ncbi.nlm.nih.gov/18061058/ https://pubmed.ncbi.nlm.nih.gov/18061058/ [9] https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.03.384 https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.03.384 [10] https://www.nature.com/articles/s41598-021-00020-3 https://www.nature.com/articles/s41598-021-00020-3 [11] https://www.ahajournals.org/doi/full/10.1161/JAHA.123.030496 https://www.ahajournals.org/doi/full/10.1161/JAHA.123.030496 [12] https://www.nature.com/articles/s41467-024-46686-x https://www.nature.com/articles/s41467-024-46686-x [13] https://www.sciencedirect.com/science/article/pii/S0021915023001144 https://www.sciencedirect.com/science/article/pii/S002191502... [14] https://link.springer.com/article/10.1186/s12872-021-01971-1 https://link.springer.com/article/10.1186/s12872-021-01971-1 [15] https://www.jstage.jst.go.jp/article/jat/31/3/31_64369/_article/-char/ja/ https://www.jstage.jst.go.jp/article/jat/31/3/31_64369/_arti...
azan_ 1y ago
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!
- breadwinner 1y ago
  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.
  - bluGill 1y ago
    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.
  - azan_ 1y ago
    > You could qualify your argument by saying that excess LDL is harmful. It’s so obvious it doesn’t need to be stated dude.
  - cthalupa 1y ago
    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
fny 1y ago
But statins are incredibly good at reducing inflammation anyway. https://pmc.ncbi.nlm.nih.gov/articles/PMC5633715/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5633715/
karlosvomacka 1y ago
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.
- timr 1y ago
  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?
- breadwinner 1y ago
  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 https://www.nytimes.com/2008/01/27/opinion/27taubes.html
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stefantalpalaru 1y ago
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dreamcompiler 1y ago
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.
- breadwinner 1y ago
  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-disease-not-about-cholesterol-businessweek-business-news-stock-market-and-financial-advice https://www.bloomberg.com/news/articles/2008-04-15/heart-dis...
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- cthalupa 1y ago
  Most of this is reputation is based on early generation statins. The side effect profile is incredibly slimmed down on statins like rosuvastatin.
pessimizer 1y ago
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.
- KempyKolibri 1y ago
  > 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.
Aurornis 1y ago
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.
- breadwinner 1y ago
  > 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.

Cholesterol and statins have always been suspect science in any case: https://medium.com/@petilon/cholesterol-and-statins-e7d9d8eea983 https://medium.com/@petilon/cholesterol-and-statins-e7d9d8ee...

bkandel 1y ago

From https://www.cochrane.org/evidence/CD004816_statins-primary-prevention-cardiovascular-disease 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.

guerby 1y ago
Published 2013
- malfist 1y ago
  The human body evolves on a much slower time scale than decades
  - guerby 1y ago
    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 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/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4836695/
    - malfist 1y ago
      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
FollowingTheDao 1y ago
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.
- KempyKolibri 1y ago
  Why do we see lower mortality in mendelian randomisation studies for individuals with SNPs that code for lower cholesterol, then?
  - FollowingTheDao 1y ago
    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/articles/10.3389/fcvm.2022.1023651/full 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.
    - cthalupa 1y ago
      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%3D10.1371/journal.pmed.1003062 https://journals.plos.org/plosmedicine/article%3Fid%3D10.137... https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00086-6/fulltext 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.bmj.com/content/342/bmj.d548 https://www.ahajournals.org/doi/10.1161/01.atv.0000258869.48076.14 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 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://pubmed.ncbi.nlm.nih.gov/25770315/ https://www.nejm.org/doi/full/10.1056/NEJMoa1604304 https://www.nejm.org/doi/full/10.1056/NEJMoa1604304
guerby 1y ago
And after 2013 in the BMJ on statins: https://www.bmj.com/campaign/statins-open-data https://www.bmj.com/campaign/statins-open-data
timr 1y ago
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.
- bluGill 1y ago
  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.
  - timr 1y ago
    > 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!

carbocation 1y ago

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.

e40 1y ago
And my understanding of the science is that statins reduce inflammation.
timr 1y ago
> 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.
- ajkjk 1y ago
  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.
  - timr 1y ago
    > 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.

Calavar 1y ago

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/192160 https://jamanetwork.com/journals/jama/article-abstract/19216... [2] https://pubmed.ncbi.nlm.nih.gov/25815993/ https://pubmed.ncbi.nlm.nih.gov/25815993/ [3] https://jamanetwork.com/journals/jamacardiology/article-abstract/2537381 https://jamanetwork.com/journals/jamacardiology/article-abst... [4] https://www.ahajournals.org/doi/abs/10.1161/01.CIR.67.4.730 https://www.ahajournals.org/doi/abs/10.1161/01.CIR.67.4.730 [5] https://jamanetwork.com/journals/jama/fullarticle/2678614 https://jamanetwork.com/journals/jama/fullarticle/2678614 [6] https://pubmed.ncbi.nlm.nih.gov/32507339/ https://pubmed.ncbi.nlm.nih.gov/32507339/ [7] https://www.tandfonline.com/doi/abs/10.1080/07315724.2008.10719668 https://www.tandfonline.com/doi/abs/10.1080/07315724.2008.10... [8] https://pubmed.ncbi.nlm.nih.gov/18061058/ https://pubmed.ncbi.nlm.nih.gov/18061058/ [9] https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.03.384 https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.03.384 [10] https://www.nature.com/articles/s41598-021-00020-3 https://www.nature.com/articles/s41598-021-00020-3 [11] https://www.ahajournals.org/doi/full/10.1161/JAHA.123.030496 https://www.ahajournals.org/doi/full/10.1161/JAHA.123.030496 [12] https://www.nature.com/articles/s41467-024-46686-x https://www.nature.com/articles/s41467-024-46686-x [13] https://www.sciencedirect.com/science/article/pii/S0021915023001144 https://www.sciencedirect.com/science/article/pii/S002191502... [14] https://link.springer.com/article/10.1186/s12872-021-01971-1 https://link.springer.com/article/10.1186/s12872-021-01971-1 [15] https://www.jstage.jst.go.jp/article/jat/31/3/31_64369/_article/-char/ja/ https://www.jstage.jst.go.jp/article/jat/31/3/31_64369/_arti...

azan_ 1y ago

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!

breadwinner 1y ago
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.
- bluGill 1y ago
  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.
- azan_ 1y ago
  > You could qualify your argument by saying that excess LDL is harmful. It’s so obvious it doesn’t need to be stated dude.
- cthalupa 1y ago
  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

fny 1y ago

But statins are incredibly good at reducing inflammation anyway. https://pmc.ncbi.nlm.nih.gov/articles/PMC5633715/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5633715/

karlosvomacka 1y ago

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.

timr 1y ago
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?
breadwinner 1y ago
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 https://www.nytimes.com/2008/01/27/opinion/27taubes.html
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stefantalpalaru 1y ago

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dreamcompiler 1y ago

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.

breadwinner 1y ago
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-disease-not-about-cholesterol-businessweek-business-news-stock-market-and-financial-advice https://www.bloomberg.com/news/articles/2008-04-15/heart-dis...
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cthalupa 1y ago
Most of this is reputation is based on early generation statins. The side effect profile is incredibly slimmed down on statins like rosuvastatin.

pessimizer 1y ago

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.

KempyKolibri 1y ago
> 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.

Aurornis 1y ago

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.

breadwinner 1y ago
> 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.