1/ Today marks my 18 month-aversary since beginning the #LCCholesterolChallengecholesterolcode.com/lccholesterolc… and exactly a year ago adding #LDLBounty to meet the challenge. To date, I've only found studies showing the opposite -> High LDL+High HDL+Low TG = Low cardiovascular disease..
2/ The reason I say "best study" in the challenge instead of "any study" is that I thought it may well be possible there were tens if not hundreds of studies that might meet the definition. Again, I've only found the opposite, like this one: ncbi.nlm.nih.gov/pubmed/27166203
3/ The colored overlays are mine, to emphasize this "triad" of high LDL, high HDL, and low triglycerides...
5/ Where they first stratified between those with an LDL of < 170 and LDL ≥ 170, then substratified three groups of high HDL+low TG, low HDL+high TG, and one in between.
6/ As it happens, the reverse of this triad already has a name in the literature, "Atherogenic Dyslipidemia", which is characterized by low HDL, high TG, and a preponderance of small dense LDL particles. It is has an extremely high association with cardiovascular disease...
7/ It's worth reminding everyone as to why I set up the challenge in the first place. I didn't pick these markers out of a hat, they are extremely relevant to the Lipid Energy Model we're working on at CC, which is central to my research and experiments. CholesterolCode.com/model
8/ I hypothesize high LDL, high HDL, and low TG generally suggests a healthy lipid metabolism. (Again, that's generally, not always) And if so, I suspect that's highly relevant to cardiovascular disease outcomes and especially all cause mortality.
9/ Getting a hold of NHANES was a game changer, as it helped to provide further evidence for this hypothesis, though with all the usual caveats that should be applied to observational data.
10/ Which brings me back to the #LCCholesterolChallenge. I'm now more skeptical than I've been before that it will be met. The bigger question is whether this will apply to those with *very* extraordinary levels of the triad, and by that I mean #LMHRsCholesterolCode.com/lmhr
11/ While I'm cautiously optimistic, I certainly emphasize that only real, clinical trial data will provide strong evidence. This is why I'm working very hard to make that happen as soon as possible.
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🧵 My thoughts on the Baseline Piece of the Puzzle
-- That everyone keeps missing... 1/10
A week ago today the longitudinal paper for our KETO-CTA study dropped (jacc.org/doi/10.1016/j.…) and there's been a lot of positive feedback, but also critiques worth discussing. I'd like to zero in on the topic of NCPV and PAV change.
First and foremost, I’m looking to be respectful of lead author Dr. Adrian Soto-Mota (@AdrianSotoMota) and Principal Investigator Dr. Matthew Budoff (@BudoffMd) regarding the complexity and relevance the heterogeneity of the cohort with regard to our findings. The coming paper expanding on this for both classification and clinical use is already under submission for review.
However, waiting for the publication of the new paper seems very untenable given how long these things take and interest in discussing the overall change in NCPV and PAV for the KETO-CTA study.
This can be challenging on my end as I want to represent this study effectively. And that’s difficult right now when I not as versed to delve deeper into both the heterogeneity relevance statistics like Dr. Soto-Mota or the issues with looking to changes in NCPV or PAV at low baseline levels like Dr. Budoff.
However, here’s what I can speak to…
I can speak to my own personal challenges in looking to the change of NCPV and PAV overall and why this hasn’t made sense to me. Not from a standpoint of discouragement, such as — this makes the study look bad. No, I mean it actually doesn’t fit any model I’m aware of save present plaque being predictive of future plaque change.
Let me unpack what I’m talking about…
Our baseline scans from the study showed this was a low risk population. Again, if looking at this from a population level.
But then, we were able to do a match analysis with Miami Heart. Matching up age, sex, ethnicity and risk factors quite tightly, but with our cohort having an average LDL-C of 272 mg/dL, and the matched Miami Heart cohort having average LDL-C of 123 mg/dL. And what did we find? They were nearly identical. In fact, for the semi-quantitative data ours was trending slightly better. jacc.org/doi/10.1016/j.…
2/10 - Moreover, while unpublished, I was cleared to present a preliminary quantitative match analysis with Miami Heart last year at a conference. These would make use of Cleerly scan data for both our cohort and Miami Heart. So it had both overall plaque volume and non calcified plaque volume (NCPV).
3/10 - But even better, there was a subgroup analysis that excluded those taking cholesterol lowering medication on Miami Heart to match again with ours...
First, let me say that data on this has been a bit limited. But *IF* we do ultimately confirm there are more ApoB-48 (B48) than ApoB-100 (B100) in ASCVD plaque, it would be a very big deal.
Let's unpack...
2/ First, thanks to @TuckerGoodrich for pinging me on these pubs and pressing the discussion.
But also credit to @CaloriesProper on tweeting this a couple years ago (I missed it then)
To understand why this would be so important if true, some review...
3/ B48 and B100s are the major proteins on chylomicrons (CMs) and VLDLs, respectively.
CMs mostly carry lipids from the small intestine to the bloodstream (lipids consumed), VLDL mostly carry lipids from storage; predominantly from adipose stores.
#Me: Why would triglyceride rich LDL particles be more atherogenic than triglyceride poor LDL particles?
#ChatGPT: Triglyceride-rich LDL (low-density lipoprotein) particles are more atherogenic (i.e., more likely to contribute to the… twitter.com/i/web/status/1…
2/
#Me: Couldn’t it also be possible that triglyceride rich LDL are ultimately the result of metabolic dysfunction and that better explains its association with atherosclerosis?
#Me: Is it possible that almost the entire amount of atherogenesis associated with high triglyceride rich LDL is due to dysfunctional lipid metabolism and the diseases that result in these profiles rather than the LDL particles themselves?
1/🧵 I'm definitely a fan of both @DominicDAgosti2 and @DrRagnar (obviously), so I was excited to see them chatting about #lipids, #LMHRs, and Dom's consideration of increasing carbs to lower his #ApoB
3/ When chatting with Dom in SD last year for dinner, he mentioned focusing less on maintaining such a sizable muscle mass as he typically does, and I predicted he'd likely see his LDL/ApoB as considerably higher with this change if still #keto. This podcast appears to confirm...