- I consider myself an optimist, but I’ve been a little less so lately. For example, as much as there are things to be concerned about right now, I’m looking toward all the economic fallout ahead and... it wont likely be rosy.
2/ - There’s at least a dozen times I’ve wanted to complain openly about how the pandemic really disrupted my plans for #TheCCDoc, the CSF study and several key experiments.
But that’s so tiny compared to many of the friends I personally know whose businesses have gone under.
3/ - On a lighter note, My friend Bill was in from out of town and wanted to play some poker with me at the casinos who now allow for five handed games.
Everyone is required to wear masks, and the dealer provides mandatory hand sanitizer every time someone returns to the table.
4/ - Maybe it’s just my imagination, but for as much as Twitter has a reputation for getting Intensively argumentative — this moment in time feels about 3X more so than any other. Even many of the people I consider to be even keel are showing a lot more edge lately.
5/ - I’m still very interested in what lipid levels are pre-infection versus post COVID-19 outcome severity.
OK, I guess that wasn’t a random thought – more of a central one.
But imagine a world where I could just go get that data – right now.
6/ - This last Sunday my wife and I built a Lego “Hulk Buster” as a fun bonding activity. I figured it take an hour to two hours... nope! That was an all day affair. But I will say it was quite a lot of fun and a welcome distraction.
7/ - Speaking of comic book movies, while I am a true blue #Marvel fan, I’ll concede I’m excited about this #Snydercut actually happening. If you don’t know what it is, follow the hashtag.
8/ - In the evenings I have occasionally watched some episodes of Alone. It’s a show that puts 10 contestants out by themselves in the wilderness to survive as long as they can stand it. It’s surprisingly more entertaining than I’d have guessed...
9/ ... The show has occasional “Med Checks” where they visit for a moment and take vitals. They then have discretion to pull a contestant, such as if they get too underweight (rightly so)
Of course, I secretly want to see what their comparative blood work is entry vs exit
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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...