4 ms·

Sure, that’s fair. I believe that ApoB-tagged lipoproteins are a causal agent in atherosclerosis via the mechanism laid out in the 2019 EAS consensus (that is,

Sure, that’s fair. I believe that ApoB-tagged lipoproteins are a causal agent in atherosclerosis via the mechanism laid out in the 2019 EAS consensus (that is, the response to retention hypothesis). The full pathway and supporting evidence can be found here: https://academic.oup.com/eurheartj/article/41/24/2313/5735221 https://academic.oup.com/eurheartj/article/41/24/2313/573522...

nradov 2y ago
Sure, no argument with that but let's go another step back in the casual chain. What's causing the arterial wall injury (or loss of ability to repair damage) in the first place to even allow that mechanism to come into play? If a patient is already accumulating arterial wall damage then it might be necessary to limit serum cholesterol through dietary changes or statins or something. But I would claim that those interventions usually come too late, and that most of the damage can be prevented through other interventions thus making serum cholesterol levels less relevant. It's like if you have a truck driving around full of toxic waste. Maybe that's cause for concern, but if you can take other measures to ensure it won't crash and spill the cargo then maybe it's fine.
- KempyKolibri 2y ago
  What’s the evidence that this only takes place in individuals with arterial wall injury or without the ability to repair damage? These factors may increase the effect of high LDL-c on CVD, but I’m not sure on what basis we should assume that those without them aren’t at risk from high LDL-c.
  - jodrellblank 2y ago
    > "What’s the evidence that this only takes place in individuals with arterial wall injury or without the ability to repair damage?" Some people live a long time with high(er) fat diets and no heart disease; Cardiologist Dr William Davis[1] selling his heart-scan plan using non-invasive CT scan / calcium measuring as a proxy for atherosclerotic plaque buildup claims that cholesterol is "virtually worthless" for predicting heart disease, and that taking statins or cutting the fat in your diet measurably "does nothing" to affect that measure of plaque buildup. Your suggestion is that cutting fat should do something. He claims his plan of removing wheat, grains, using fish oil, fixing inflammation and insulin resistance, various vitamins and minerals, can measurably stop plaque developing and it can reduce. That seems like it should be a very testable claim. I haven't read his books, don't know the details of his plan, but if calcium is a solid proxy for plaque buildup, and a CT scan can measure it stay the same in people who switch to low-fat diets, and measure it drop in some people who don't but instead remove grains, that suggests plaque buildup from LDL only takes place in some individuals who eat fat, not all. Arterial wall injury or inability to repair damage are they possible reasons? Or the inflammation and insulin resistance he mentions? [1] https://drdavisinfinitehealth.com/2019/03/why-you-should-get-a-ct-heart-scan/ https://drdavisinfinitehealth.com/2019/03/why-you-should-get...
    - KempyKolibri 2y ago
      That’s an answer to a different question. I don’t disagree that CVD risk is multi factorial - having T2DM massively increases the risk, for example. But this being the case does not serve as evidence that arterial wall injury or an inability to repair damage is required in order for high serum cholesterol to be a risk. CAC scores (which it sounds like what you’re referring to) only look at calcified plaque, but not soft plaques. So there’s a whole category of risk that is missed by them. People’s CAC only tends to go up when they’re in a very late stage of atherosclerosis, and calcified plaques also tend to be more stable than soft plaques, so if two individuals had the same mass of plaque, but one’s was soft and the other’s one’s hard (sorry for the “carry on cardiology”) then we’d actually expect the individual with the CAC score of zero to be at greater risk of a CVD event. It’s my interlocutor’s burden to show that arterial wall damage and/or an individual’s inability to repair damage is required for ASCVD to take hold, and so far they’ve yet to meet it. That’s what I’m looking for, basically.
      - jodrellblank 2y ago
        Sounds like CAC scores are the same thing. I can only link some other doctor's article[1] which says that the CAC does only measures hard plaque, but that a score of 0 has been studied and goes with a very low risk of heart attack (1-2%) over the next ten years. When you say soft plaques are a whole category of risk, that suggests they are not a significant risk factor. So something doesn't add up here. From what I could gain in the paper you linked in another comment, they write that apoB with less LDL in it goes more easily into the arterial wall, apoB with more LDL in it causes more damage once in the arterial wall, and those two effects cancel out, so overal more LDL is worse. These things don't add up to a coherent picture. If eating less fat reduced LDL, that should reduces plaque buildup (by your claims and your study's claims) and that should reduces heart disease risk, and that should show up in the CAC scans. And apparently it doesn't. If eating more fat increases LDL and that increases heart disease risk, that should show up in Dr Davis' CAC scans and he should think that worsens heart disease risk, and he doesn't. > "But this being the case does not serve as evidence that arterial wall injury or an inability to repair damage is required in order for high serum cholesterol to be a risk." It doesn't, and I don't make that claim. So I have no more comment. Agree that it's multifactorial (or appears that way). [1] https://myheart.net/articles/ct-coronary-artery-calcium-heart-scan-the-facts/ https://myheart.net/articles/ct-coronary-artery-calcium-hear...

nradov 2y ago

Sure, no argument with that but let's go another step back in the casual chain. What's causing the arterial wall injury (or loss of ability to repair damage) in the first place to even allow that mechanism to come into play? If a patient is already accumulating arterial wall damage then it might be necessary to limit serum cholesterol through dietary changes or statins or something. But I would claim that those interventions usually come too late, and that most of the damage can be prevented through other interventions thus making serum cholesterol levels less relevant. It's like if you have a truck driving around full of toxic waste. Maybe that's cause for concern, but if you can take other measures to ensure it won't crash and spill the cargo then maybe it's fine.

KempyKolibri 2y ago
What’s the evidence that this only takes place in individuals with arterial wall injury or without the ability to repair damage? These factors may increase the effect of high LDL-c on CVD, but I’m not sure on what basis we should assume that those without them aren’t at risk from high LDL-c.
- jodrellblank 2y ago
  > "What’s the evidence that this only takes place in individuals with arterial wall injury or without the ability to repair damage?" Some people live a long time with high(er) fat diets and no heart disease; Cardiologist Dr William Davis[1] selling his heart-scan plan using non-invasive CT scan / calcium measuring as a proxy for atherosclerotic plaque buildup claims that cholesterol is "virtually worthless" for predicting heart disease, and that taking statins or cutting the fat in your diet measurably "does nothing" to affect that measure of plaque buildup. Your suggestion is that cutting fat should do something. He claims his plan of removing wheat, grains, using fish oil, fixing inflammation and insulin resistance, various vitamins and minerals, can measurably stop plaque developing and it can reduce. That seems like it should be a very testable claim. I haven't read his books, don't know the details of his plan, but if calcium is a solid proxy for plaque buildup, and a CT scan can measure it stay the same in people who switch to low-fat diets, and measure it drop in some people who don't but instead remove grains, that suggests plaque buildup from LDL only takes place in some individuals who eat fat, not all. Arterial wall injury or inability to repair damage are they possible reasons? Or the inflammation and insulin resistance he mentions? [1] https://drdavisinfinitehealth.com/2019/03/why-you-should-get-a-ct-heart-scan/ https://drdavisinfinitehealth.com/2019/03/why-you-should-get...
  - KempyKolibri 2y ago
    That’s an answer to a different question. I don’t disagree that CVD risk is multi factorial - having T2DM massively increases the risk, for example. But this being the case does not serve as evidence that arterial wall injury or an inability to repair damage is required in order for high serum cholesterol to be a risk. CAC scores (which it sounds like what you’re referring to) only look at calcified plaque, but not soft plaques. So there’s a whole category of risk that is missed by them. People’s CAC only tends to go up when they’re in a very late stage of atherosclerosis, and calcified plaques also tend to be more stable than soft plaques, so if two individuals had the same mass of plaque, but one’s was soft and the other’s one’s hard (sorry for the “carry on cardiology”) then we’d actually expect the individual with the CAC score of zero to be at greater risk of a CVD event. It’s my interlocutor’s burden to show that arterial wall damage and/or an individual’s inability to repair damage is required for ASCVD to take hold, and so far they’ve yet to meet it. That’s what I’m looking for, basically.
    - jodrellblank 2y ago
      Sounds like CAC scores are the same thing. I can only link some other doctor's article[1] which says that the CAC does only measures hard plaque, but that a score of 0 has been studied and goes with a very low risk of heart attack (1-2%) over the next ten years. When you say soft plaques are a whole category of risk, that suggests they are not a significant risk factor. So something doesn't add up here. From what I could gain in the paper you linked in another comment, they write that apoB with less LDL in it goes more easily into the arterial wall, apoB with more LDL in it causes more damage once in the arterial wall, and those two effects cancel out, so overal more LDL is worse. These things don't add up to a coherent picture. If eating less fat reduced LDL, that should reduces plaque buildup (by your claims and your study's claims) and that should reduces heart disease risk, and that should show up in the CAC scans. And apparently it doesn't. If eating more fat increases LDL and that increases heart disease risk, that should show up in Dr Davis' CAC scans and he should think that worsens heart disease risk, and he doesn't. > "But this being the case does not serve as evidence that arterial wall injury or an inability to repair damage is required in order for high serum cholesterol to be a risk." It doesn't, and I don't make that claim. So I have no more comment. Agree that it's multifactorial (or appears that way). [1] https://myheart.net/articles/ct-coronary-artery-calcium-heart-scan-the-facts/ https://myheart.net/articles/ct-coronary-artery-calcium-hear...