At one point you say that the metabolic syndrome is correlated with insulin resistance, and at another point you use IR as another word for the metablic syndrome. It's important to be clear, as you pointed out. (Btw, when I say "high cholesterol," I mean elevated LDL-C.) The correlation coefficient between ApoB and repeat LDL-C measurements is high enough as to make the (more expensive) ApoB not worth measuring except for research purposes; though I'd be happy to measure ApoB directly, doing so would change very little. It's certainly not "much better." There is actual research, and then there is clinical junk like taking ratios of different lipoprotein species; that doesn't help you get to the heart of the problem. And you are extrapolating out too far from the papers that you are citing; the medical literature merits a bit more of a cautious reading than I think you're giving it, IMHO. Making super-bold claims like "Metabolic syndrome ... is the "best" predcursor/predictor for cardiac mortality" from a paper entitled "Evaluation of some markers of subclinical atherosclerosis in Egyptian young adult males with abdominal obesity" is a perfect example of over-interpreting.
In conclusion, your level of belief of well-established science (such as statin trials; >100,000 people, total) is too low, and your willingness to extrapolate from very small studies (50 people, total) is too high. I would urge you to recalibrate your beliefs in proportion to the weight of each study, instead of in proportion to your desire for the study to be true. It's hard for all of us to do, but it's the hallmark of the scientific approach.
> Making super-bold claims like "Metabolic syndrome ... is the "best" predcursor/predictor for cardiac mortality" .. example of over-interpreting.
That is an unfair charge, the claim is not based solely on that study. Taubes reviews 50+ years of observations and research on this. Besides, that claim is my hypothesis, which is yet to be tested.
I in no way present it as anything other than a theory.
> In conclusion, your level of belief of well-established science (such as statin trials; >100,000 people, total)
Citation?
> is too low, and your willingness to extrapolate from very small studies (50 people, total) is too high.
I will grant that this is the case. It's because the large scale studies for the hypothesis I put forward do not exist yet. I would like to see NIH funded diet-intervention studies at the same scale, even n=200 would be a great thing.
> each study, instead of in proportion to your desire for the study to be true. It's hard for all of us to do, but it's the hallmark of the scientific approach.
Nice burn in the last sentence!
While I agree that my hypothesis has not been tested, it has not been negated either.
I would like to see well funded and well designed studies to settle the issue conclusively, therefore the charge about the scientific approach is a bit off the mark: I am not holding on to a belief in the face of overwhelming evidence against it, I merely postulate an alternative hypothesis which has the potential to neatly (in the Occam's razor sense) explain several inconsistencies in the current model (and should be tested for merely on that basis, if for no other).
The ApoB issue was raised as there were some pubmed papers that discussed the test and what advantages it had over others in predictive power. I cannot find the ref. right now, but it should be easy to search for. In any case, that was a tangential point I made and you spend a lot of time addressing it, while not addressing other tests like homocysteine levels etc.
MS is a catch-all term for several coincidentally occuring symptoms, as far as I can tell. IR is one of them, abdominal obesity is another, prevalence of LDL and high triglyceride counts are yet more markers. For all I know, IR is the major symptom, that's why at one point I refer to IR and then say "aka MS". Again, this point is tangential.
When you said "Cholesterol" I naturally assumed "Total Cholesterol". I note that you have clarified that. Also, LDL-C I presume includes the VLDL counts? That raises another possible issue: what if the symptoms observed in these studies actually indicate that VLDL is highly correlated with mortality, and that due to some confounding factor, the subjects in these studies have very high VLDL? In that case LDL would be unfairly blamed. Do you agree?
> Looking at coronary calcification is no better than looking at lipoprotein fractions; both are intermediate endpoints. I see no reason to trust calcification if you don't trust LDL. Reduction in LDL correlates so well with ... FDA-got-bought-out-by-pharma sort of problem.
You did not address the Agatston score point, which iirc was the main rebuttal I'd made to your earlier comment. As this discussion is threatening to run off on another tangent, I will end here.
> To reject the overwhelmingly data-backed LDL hypothesis, I'd need to see something much more compelling, I must say.
Perhaps GCBC may itself be compelling?
I will state that most of my stance is covered in GCBC (to the extent that you could say I got it from there) and it should be quite easy to test the alternative hypotheses laid out in that book. Perhaps we can revisit this thread when the issue is settled to our satisfactions and marvel at the different positions we took.
No, it's completely fair. We have objective criteria for evaluating "best", and expert opinion is Grade C evidence (different groups use different lettering conventions, but suffice it to say that expert opinion is not regarded highly since it is, in fact, not evidence).
LDL is not VLDL. LDL-C is different from VLDL measures. Since this isn't that popularly known, let me explain a bit: people rarely measure LDL-C directly. Instead, they assume that virtually all serum TG is carried by VLDL; they measure HDL; and then they infer LDL-C. It turns out that this inferred LDL-C correlates well enough with directly measured LDL-C for the vast majority of people that it hasn't been worth the cost of implementing a direct test except for research purposes (Canadians will differ on this).
I'm not exactly sure where you are going with the VLDL vs LDL discussion, however, since VLDL is the precursor to LDL. It is always a formal possibility that a confounder is modifying or even inverting the relationship between X and Y, but typically one would expect some evidence in support of that. The LDL-MI association holds up in every population tested - so unless this postulated confounder is present in every population, it's not likely. Plus, most people expect that both VLDL and LDL will correlate with MI risk, though the best studied one is LDL.
>You did not address the Agatston score point, which iirc was the main rebuttal I'd made to your earlier comment. As this discussion is threatening to run off on another tangent, I will end here.
My point isn't that the Agatston score is bad; it's that you're rejecting the intermediate endpoint with the best evidence (LDL-C, which has prospective randomized trials supporting it) and then endorsing an intermediate endpoint that's far less accepted (coronary calcification). I rebutted your Agatston score comment in a couple of ways previously and without actual evidence supporting its importance in the causal chain for MI, I see it merely as a biomarker (unlike LDL-C, which is causal).
>Perhaps GCBC may itself be compelling?
No. Since the GCBC is a book that expresses its author's expert opinion, I do not find it to be evidence. When I hear "evidence," I expect data, not opinion.
In conclusion, your level of belief of well-established science (such as statin trials; >100,000 people, total) is too low, and your willingness to extrapolate from very small studies (50 people, total) is too high. I would urge you to recalibrate your beliefs in proportion to the weight of each study, instead of in proportion to your desire for the study to be true. It's hard for all of us to do, but it's the hallmark of the scientific approach.