5 ms·

Cholesterol / lipid science is a mess. First it was LDL-C that was bad, then that doesn’t actually correlate, then it’s LDL-P, oh wait, then it’s LDL size, and

Cholesterol / lipid science is a mess. First it was LDL-C that was bad, then that doesn’t actually correlate, then it’s LDL-P, oh wait, then it’s LDL size, and then it’s ApoB that’s going to “clog your arteries”. Once you dive into the “hard” science like pathology of atherosclerosis, you’ll find that the lipid hypothesis makes no sense. We have drugs (PKCS9 inhibitors: https://www.nejm.org/doi/full/10.1056/NEJMoa1615664 https://www.nejm.org/doi/full/10.1056/NEJMoa1615664, bile acid sequesterants, CETP Inhibitors: https://www.nejm.org/doi/full/10.1056/NEJMoa1609581 https://www.nejm.org/doi/full/10.1056/NEJMoa1609581) that can lower LDL to 10-20mg/dL — the later even increased HDL. No impact on cardiovascular mortality. The studies all use composite endpoints. What might cause Atherosclerosis? - Bacteria - Bacterial lipid byproducts - Endothelial damage from toxins (lead, mecury, etc) - Endothelial glycation from high blood sugar (Diabetics have a lot of CVD) - Bad genetics resulting in excess hemodynamic stress at coronary branch points (fun fact: CVD only develops in a few specific spots) - Autoimmune conditions (higher rates of CVD in this population) What most of these things have in common is they trigger the activation of the immune system.

village-idiot 7y ago
For the life of me I really don’t understand why the regulators haven’t clamped down on statins. Sure, it lowers your cholesterol, but unless if you’re in a very specific population it doesn’t move your all cause mortality risk one iota. All while costing the patient money and causing some pretty nasty side effects too.
- viraptor 7y ago
  > but unless if you’re in a very specific population it doesn’t move your all cause mortality risk one iota Have you got a link to some relevant research?
  - village-idiot 7y ago
    Sure do! I typically defer to Mark Sisson for this kind of stuff, who’s very good at linking in relevant research. https://www.marksdailyapple.com/the-evidence-continues-to-mount-against-statins/ https://www.marksdailyapple.com/the-evidence-continues-to-mo...
- semenko 7y ago
  Probably because most data disagree with this comment. There's a ~20% relative risk reduction in vascular events & mortality per ~40 mg/dL decrease in LDL. The CTT is probably the best summary of these data: https://www.cttcollaboration.org/ https://www.cttcollaboration.org/
  - virtuallynathan 7y ago
    > "~20% relative risk reduction in vascular events & mortality per ~40 mg/dL decrease in LDL." Is that a composite endpoint of vascular events AND mortality? From TheNNT: "It takes 5 years of daily statin therapy to achieve a 1.6% chance of avoiding a heart attack, and a 0.37% chance of avoiding a stroke. Most disappointing, statins seem unable to prevent death in this group. And most concerning, the drugs may increase diabetes, a serious and life-altering disease." (Primary Prevention) http://www.thennt.com/nnt/statins-for-heart-disease-prevention-without-prior-heart-disease-2/ http://www.thennt.com/nnt/statins-for-heart-disease-preventi...
  - deleted 7y ago
    [deleted]
  - village-idiot 7y ago
    That would be the same CTT that makes money from the makers of Statins and has been accused of being insufficiently transparent around their studies[0]. 0 http://www.drjohnm.org/2014/06/growing-doubt-on-statin-drugs-the-problem-of-drug-lifestyle-interaction/ http://www.drjohnm.org/2014/06/growing-doubt-on-statin-drugs...
agumonkey 7y ago
I thought I'd double down on reading medical books and the more I read the less I knew. The deeper the fuzzier.
YeGoblynQueenne 7y ago
Well, the study in the posted article examined Total Cholesterol (TC), not LDL, and the conflicting results you say were found in different studies were all about LDL, which suggests there really is some involvement of LDL in CVD. I wonder whether you might have misinterpreted these studies as conflicting when they are merely complementary in nature. Additionally, I think you will not find many studies that claim that high HDL is bad for you, whereas you will find many that claim it's good (because it protects from CVD). I can't say I see much of "a mess" here- just ordinary, progressing scientific understanding of a complex system. Are there really any studies that attribute atherosclerosis to bacteria, or some of the other conditions you describe? If so- are there many of those and are they good quality studies? I am very skeptical of your comment's suggestion that the immune system may be involved in atherosclerosis.
- virtuallynathan 7y ago
  My comment is more general, not specifically in response to the specifics of the article on TC. FWIW, TC is probably not a great measure on an individual basis, but sort of interesting population-wide. Yes, folks agree high HDL is good, high LDL is bad. However, drug trials to raise HDL didn't work so well. > "Are there really any studies that attribute atherosclerosis to bacteria, or some of the other conditions you describe?" Yes! Many! - "Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases" https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.104.507996 https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.... - "Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis" - "The immune system in atherosclerosis" https://www.nature.com/articles/ni.2001 https://www.nature.com/articles/ni.2001 - "Is atherosclerosis an autoimmune disease?" https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-12-47 https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-... - "Atherosclerosis and the role of immune cells" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391004/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391004/
  - YeGoblynQueenne 7y ago
    Thank you for the links. My understanding is also that TC is not a very good predictor of cardiovascular health, but I'm not any kind of expert on the matter, or even close.
mtgx 7y ago
This is a relevant video to some of the stuff you said: https://www.youtube.com/watch?v=vBKa6d6j9_8 https://www.youtube.com/watch?v=vBKa6d6j9_8
deleted 7y ago
[deleted]
carbocation 7y ago
Just so other readers are aware, this view of cholesterol and lipidology is far outside the mainstream medical understanding of the topic. LDL-c is bad. LDL-p (the particle number), LDL size, and ApoB (which is the protein part of LDL) are all very well correlated with LDL-c. So, while some people prefer one measurement or another, they're all proxies for one another. We have lifelong exposure to our genetics-and-diet-induced cholesterol levels, whereas clinical trials run for a few years. The long-term follow up of the statin trials show mortality reduction. PCSK9 inhibitors reduce all-cause mortality, and the long-term follow-up of the PCSK9 trials may or may not show the same for cardiovascular specific mortality. However, everyone in the field thinks they will, because those with loss-of-function PCSK9 variants live longer with less cardiovascular disease. Also, adjudicating the cause of death is hard - autopsy, if done, overturns the diagnosis nearly 60% of the time[1]. Cholesterol isn't the only risk factor for cardiovascular disease, so other things (like autoimmune conditions) will contribute to risk as well, but this isn't an either/or phenomenon. 1 = https://www.ncbi.nlm.nih.gov/pubmed/12913844 https://www.ncbi.nlm.nih.gov/pubmed/12913844
- keymone 7y ago
  If LDL-c correlated with LDL-p, those two metrics would have been similarly good as CVD predictors, but they aren’t, LDL-c is basically useless. (Don’t have sources atm, can link later if you’re interested)
  - carbocation 7y ago
    This is simply incorrect.
    - keymone 7y ago
      https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391 https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1...
- Joeri 7y ago
  Do the statin follow-up studies correct for participants seeing a doctor more often? Even if the statins do nothing I would expect mortality to be lower among the group that takes them just by having more interactions with doctors.

village-idiot 7y ago

For the life of me I really don’t understand why the regulators haven’t clamped down on statins. Sure, it lowers your cholesterol, but unless if you’re in a very specific population it doesn’t move your all cause mortality risk one iota. All while costing the patient money and causing some pretty nasty side effects too.

viraptor 7y ago
> but unless if you’re in a very specific population it doesn’t move your all cause mortality risk one iota Have you got a link to some relevant research?
- village-idiot 7y ago
  Sure do! I typically defer to Mark Sisson for this kind of stuff, who’s very good at linking in relevant research. https://www.marksdailyapple.com/the-evidence-continues-to-mount-against-statins/ https://www.marksdailyapple.com/the-evidence-continues-to-mo...
semenko 7y ago
Probably because most data disagree with this comment. There's a ~20% relative risk reduction in vascular events & mortality per ~40 mg/dL decrease in LDL. The CTT is probably the best summary of these data: https://www.cttcollaboration.org/ https://www.cttcollaboration.org/
- virtuallynathan 7y ago
  > "~20% relative risk reduction in vascular events & mortality per ~40 mg/dL decrease in LDL." Is that a composite endpoint of vascular events AND mortality? From TheNNT: "It takes 5 years of daily statin therapy to achieve a 1.6% chance of avoiding a heart attack, and a 0.37% chance of avoiding a stroke. Most disappointing, statins seem unable to prevent death in this group. And most concerning, the drugs may increase diabetes, a serious and life-altering disease." (Primary Prevention) http://www.thennt.com/nnt/statins-for-heart-disease-prevention-without-prior-heart-disease-2/ http://www.thennt.com/nnt/statins-for-heart-disease-preventi...
- deleted 7y ago
  [deleted]
- village-idiot 7y ago
  That would be the same CTT that makes money from the makers of Statins and has been accused of being insufficiently transparent around their studies[0]. 0 http://www.drjohnm.org/2014/06/growing-doubt-on-statin-drugs-the-problem-of-drug-lifestyle-interaction/ http://www.drjohnm.org/2014/06/growing-doubt-on-statin-drugs...

agumonkey 7y ago

I thought I'd double down on reading medical books and the more I read the less I knew. The deeper the fuzzier.

YeGoblynQueenne 7y ago

Well, the study in the posted article examined Total Cholesterol (TC), not LDL, and the conflicting results you say were found in different studies were all about LDL, which suggests there really is some involvement of LDL in CVD. I wonder whether you might have misinterpreted these studies as conflicting when they are merely complementary in nature. Additionally, I think you will not find many studies that claim that high HDL is bad for you, whereas you will find many that claim it's good (because it protects from CVD). I can't say I see much of "a mess" here- just ordinary, progressing scientific understanding of a complex system. Are there really any studies that attribute atherosclerosis to bacteria, or some of the other conditions you describe? If so- are there many of those and are they good quality studies? I am very skeptical of your comment's suggestion that the immune system may be involved in atherosclerosis.

virtuallynathan 7y ago
My comment is more general, not specifically in response to the specifics of the article on TC. FWIW, TC is probably not a great measure on an individual basis, but sort of interesting population-wide. Yes, folks agree high HDL is good, high LDL is bad. However, drug trials to raise HDL didn't work so well. > "Are there really any studies that attribute atherosclerosis to bacteria, or some of the other conditions you describe?" Yes! Many! - "Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases" https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.104.507996 https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.... - "Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis" - "The immune system in atherosclerosis" https://www.nature.com/articles/ni.2001 https://www.nature.com/articles/ni.2001 - "Is atherosclerosis an autoimmune disease?" https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-12-47 https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-... - "Atherosclerosis and the role of immune cells" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391004/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391004/
- YeGoblynQueenne 7y ago
  Thank you for the links. My understanding is also that TC is not a very good predictor of cardiovascular health, but I'm not any kind of expert on the matter, or even close.

mtgx 7y ago

This is a relevant video to some of the stuff you said: https://www.youtube.com/watch?v=vBKa6d6j9_8 https://www.youtube.com/watch?v=vBKa6d6j9_8

deleted 7y ago

[deleted]

carbocation 7y ago

Just so other readers are aware, this view of cholesterol and lipidology is far outside the mainstream medical understanding of the topic. LDL-c is bad. LDL-p (the particle number), LDL size, and ApoB (which is the protein part of LDL) are all very well correlated with LDL-c. So, while some people prefer one measurement or another, they're all proxies for one another. We have lifelong exposure to our genetics-and-diet-induced cholesterol levels, whereas clinical trials run for a few years. The long-term follow up of the statin trials show mortality reduction. PCSK9 inhibitors reduce all-cause mortality, and the long-term follow-up of the PCSK9 trials may or may not show the same for cardiovascular specific mortality. However, everyone in the field thinks they will, because those with loss-of-function PCSK9 variants live longer with less cardiovascular disease. Also, adjudicating the cause of death is hard - autopsy, if done, overturns the diagnosis nearly 60% of the time[1]. Cholesterol isn't the only risk factor for cardiovascular disease, so other things (like autoimmune conditions) will contribute to risk as well, but this isn't an either/or phenomenon. 1 = https://www.ncbi.nlm.nih.gov/pubmed/12913844 https://www.ncbi.nlm.nih.gov/pubmed/12913844

keymone 7y ago
If LDL-c correlated with LDL-p, those two metrics would have been similarly good as CVD predictors, but they aren’t, LDL-c is basically useless. (Don’t have sources atm, can link later if you’re interested)
- carbocation 7y ago
  This is simply incorrect.
  - keymone 7y ago
    https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391 https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1...
Joeri 7y ago
Do the statin follow-up studies correct for participants seeing a doctor more often? Even if the statins do nothing I would expect mortality to be lower among the group that takes them just by having more interactions with doctors.