4 ms·

(caveat:I'm not an expert) Why would you need to account for it? Trying to understand the logic here. The study goes to showing the association between high c

(caveat:I'm not an expert) Why would you need to account for it? Trying to understand the logic here. The study goes to showing the association between high cholesterol and all-cause mortality (which is what we really care about right?) is weak. This would seem to diminish the benefits of statin use, all other things being equal.

carbocation 7y ago
In the tweet that I linked to, we noted that failure to account for statin use can invert the causal relationship between cholesterol and mortality. With regard to the point of the study, they start by saying, "It is unclear whether associations between total cholesterol (TC) levels and all-cause mortality and the optimal TC ranges for lowest mortality vary by sex and age." So, interpreting their statement, I would say that their goal with this study was to investigate whether the relationship between total cholesterol and mortality was consistent across age and sex. That is a different point from assessing the strength of the relationship between cholesterol and mortality. I do agree, however, that there is no single biomarker aside from age that is a particularly powerful predictor of mortality in the general population.
- fauigerzigerk 7y ago
  I don't understand why it matters for the conclusion whether lower cholesterol (or specifically LDL) is caused by diet or statins or something else altogether (if the assumption is that high LDL affects mortality). [Edit] I just read another one of your comments that answers my question, and I think you're right: https://news.ycombinator.com/item?id=20138685 https://news.ycombinator.com/item?id=20138685
- garmaine 7y ago
  Age isn’t a bio marker.
  - carbocation 7y ago
    I agree, it doesn’t fit the definition. I still call it that in casual conversation when getting the point across while being more precise would be more wordy.
    - garmaine 7y ago
      It is fundamentally not the same though. You are saying that there isn’t any reliable bio marker other than “age,” but you can’t measure age. So what reliable bio marker are you talking about? What would be measured? If you mean there are no reliable bio markers, period, it would be more clear to just say that.
      - Amygaz 7y ago
        I tend to disagree. We actually can measure the biological age. There are clinical biomarkers for that. It is not commonly done. The best one, epigenetic signature, is yet to be clinically approved or widely available. Now, in that paper, they use broad range of age as a descriptor, confounding many age-associated phenotype and genotypes, which also translate into risk factors. You can definitely say that the 18-34 cohort is different 45-54, and that the later as more risk factors, the same a specific mutation might be associated with higher or even guaranteed chance of developing a disease, and hence will be use as a biomarker. That being said, it is not typical to measure the biological age of healthy individuals. Actually, we don't know what an healthy individual is. We know a great deal more about diseased individuals. The current status seems to be that if you are not diseased you are healthy. I don't agree with that. That's how science is done. And that is how we end up with half-baked studies in one of the most impactful journal .
        naasking 7y ago
        > We actually can measure the biological age. There are clinical biomarkers for that. It is not commonly done. The best one, epigenetic signature, is yet to be clinically approved or widely available. What is the precision and accuracy of the best biomarker? ie. if I gave you the necessary sample, how close can you get to the correct age and what are the error bars?
- phkahler 7y ago
  >> In the tweet that I linked to, we noted that failure to account for statin use can invert the causal relationship between cholesterol and mortality. I didn't get enough from the tweets to understand how that was accounted for in the data. But I have questions. By "inverts the causal relationship" I assume you threw "causal" in there by mistake. Nobody is going to think mortality causes high cholesterol. More importantly, if ignoring statin use reverses the slope to weaken the relationship "high cholesterol causes mortality" doesn't that suggest a lack of efficacy for statins? We know they lower cholesterol, but if that also reduces mortality the relationship (between cholesterol and mortality) should hold weather they are accounted for or not. Right?
  - carbocation 7y ago
    > Nobody is going to think mortality causes high cholesterol. Prevalent cardiovascular disease, or having a high risk for cardiovascular disease, causes low cholesterol. It does so by your doctor recognizing your elevated risk and putting you on statins. Statins, like all drugs for prevention, do not prevent all subsequent disease. Perhaps most importantly, they only reduce cholesterol from the time you start taking them (as opposed to a genetically-driven low cholesterol throughout life). All of the drugs for chronic disease prevention tend to have a pretty small effect on the disease risk. Therefore, detecting that someone is taking a statin is a great signal that the person is at high risk for disease. They would be at an even higher risk if they weren't on a statin, but the statin does not erase all risk. That is why failing to account for statin use will lead to low cholesterol looking protective, if there are people in the population taking statins.

carbocation 7y ago

In the tweet that I linked to, we noted that failure to account for statin use can invert the causal relationship between cholesterol and mortality. With regard to the point of the study, they start by saying, "It is unclear whether associations between total cholesterol (TC) levels and all-cause mortality and the optimal TC ranges for lowest mortality vary by sex and age." So, interpreting their statement, I would say that their goal with this study was to investigate whether the relationship between total cholesterol and mortality was consistent across age and sex. That is a different point from assessing the strength of the relationship between cholesterol and mortality. I do agree, however, that there is no single biomarker aside from age that is a particularly powerful predictor of mortality in the general population.

fauigerzigerk 7y ago
I don't understand why it matters for the conclusion whether lower cholesterol (or specifically LDL) is caused by diet or statins or something else altogether (if the assumption is that high LDL affects mortality). [Edit] I just read another one of your comments that answers my question, and I think you're right: https://news.ycombinator.com/item?id=20138685 https://news.ycombinator.com/item?id=20138685
garmaine 7y ago
Age isn’t a bio marker.
- carbocation 7y ago
  I agree, it doesn’t fit the definition. I still call it that in casual conversation when getting the point across while being more precise would be more wordy.
  - garmaine 7y ago
    It is fundamentally not the same though. You are saying that there isn’t any reliable bio marker other than “age,” but you can’t measure age. So what reliable bio marker are you talking about? What would be measured? If you mean there are no reliable bio markers, period, it would be more clear to just say that.
    - Amygaz 7y ago
      I tend to disagree. We actually can measure the biological age. There are clinical biomarkers for that. It is not commonly done. The best one, epigenetic signature, is yet to be clinically approved or widely available. Now, in that paper, they use broad range of age as a descriptor, confounding many age-associated phenotype and genotypes, which also translate into risk factors. You can definitely say that the 18-34 cohort is different 45-54, and that the later as more risk factors, the same a specific mutation might be associated with higher or even guaranteed chance of developing a disease, and hence will be use as a biomarker. That being said, it is not typical to measure the biological age of healthy individuals. Actually, we don't know what an healthy individual is. We know a great deal more about diseased individuals. The current status seems to be that if you are not diseased you are healthy. I don't agree with that. That's how science is done. And that is how we end up with half-baked studies in one of the most impactful journal .
      - naasking 7y ago
        > We actually can measure the biological age. There are clinical biomarkers for that. It is not commonly done. The best one, epigenetic signature, is yet to be clinically approved or widely available. What is the precision and accuracy of the best biomarker? ie. if I gave you the necessary sample, how close can you get to the correct age and what are the error bars?
phkahler 7y ago
>> In the tweet that I linked to, we noted that failure to account for statin use can invert the causal relationship between cholesterol and mortality. I didn't get enough from the tweets to understand how that was accounted for in the data. But I have questions. By "inverts the causal relationship" I assume you threw "causal" in there by mistake. Nobody is going to think mortality causes high cholesterol. More importantly, if ignoring statin use reverses the slope to weaken the relationship "high cholesterol causes mortality" doesn't that suggest a lack of efficacy for statins? We know they lower cholesterol, but if that also reduces mortality the relationship (between cholesterol and mortality) should hold weather they are accounted for or not. Right?
- carbocation 7y ago
  > Nobody is going to think mortality causes high cholesterol. Prevalent cardiovascular disease, or having a high risk for cardiovascular disease, causes low cholesterol. It does so by your doctor recognizing your elevated risk and putting you on statins. Statins, like all drugs for prevention, do not prevent all subsequent disease. Perhaps most importantly, they only reduce cholesterol from the time you start taking them (as opposed to a genetically-driven low cholesterol throughout life). All of the drugs for chronic disease prevention tend to have a pretty small effect on the disease risk. Therefore, detecting that someone is taking a statin is a great signal that the person is at high risk for disease. They would be at an even higher risk if they weren't on a statin, but the statin does not erase all risk. That is why failing to account for statin use will lead to low cholesterol looking protective, if there are people in the population taking statins.