Many medical professionals (like my good friend and colleague, @DrNadolsky) feel strongly that #LowCarb-ers may be acting very recklessly by allowing their #LDL#Cholesterol to be much higher than the guidelines allow.
Certainly if "diet induced" high LDL is the equivalent to genetically high LDL, such as those with #FamilialHypercholesterolemia (FH), then there should be likewise rapidly progressing #atherosclerosis.
3/ "The sine qua non of FH is severe elevation of total and LDL cholesterol levels." jaoa.org/article.aspx?a…
Often heterozygous FH is considered where LDL is 190 to 500 mg/dL, with homozygous being above 500.
4/ Indeed, there are key symptoms they may arise in the low carb community related to high cholesterol-- the most relevant being "tendon xanthomas"
"Tendon xanthomas are a classic pathognomonic physical examination finding, detected in approximately 20% to 40% of those with FH."
5/ I won't link a picture here, but you can google "tendon xanthomas" for examples.
(Note these are different than xanthelasmas which can occur around the eyes/eyelids, but are less specific to FH -- where tendon xanthomas are very specific)
6/ Given children with homozygous FH can get tendon xanthomas at age 2 or 3, and given the lipid hypothesis considers "LDL burden" to be dose dependent and log linear over lifetime exposure- these symptoms should be showing up at very high rates for low carb hyper-responders soon
7/ Which is all the more reason to take Computed Tomography Angiography (CTA) scans in a clinical trial as soon as possible -- which is our central measurement for the study.
CTAs can display powerful, high resolution geography of the cardiovascular system.
8/ And given the effect size of "Lean Mass Hyper-responders" (LMHRs) where LDL is often well above the guidelines (>190 mg/dL -- with many in the 300s, 400s, 500s or more), we should be able to observe the same rapid progression of atherosclerosis we see with FH in just 1 year.
9/ To emphasize -- if you believe low carbers are being too cavalier with their high cholesterol -- help fund this study to bring this data back to them ASAP.
This study could potentially give notice to everyone on low carb who might need to take steps to lower their lipids.
10/ Conversely, if you yourself are low carb with high cholesterol and believe the data will show low to no risk, you should be just as motivated to get the evidence specific to this context.
In short -- help us get the data that's relevant to you.
11/ As of this thread, our funding sits at $86,472.00 on our way to $100,000 -- where we have an anonymous donor set to match with an additional $100,000 when we reach the goal. 🚨
Which is to say -- we're very, very close to having our goal of $200k to meet our base funding.
12/ There's been more than enough debate around this topic without the clinical data to its context. If many low carbers are going to maintain higher LDL regardless of the guidelines, we should capture this data ASAP to confirm its efficacy.
🧵 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...