Plaque Progression — or Lack Thereof — in LMHR, by Dr. Adrian Soto-Mota MD PhD
Plaque Progression — or Lack Thereof — in LMHR
Foreword by Coach Roxana:
This is one of the most important threads ever written on LDL cholesterol, especially for those of us following a ketogenic or low-carb lifestyle. Dr. Adrian Soto-Mota and his colleagues have published new, crowd-funded research in JACC that challenges many assumptions about cardiovascular risk and ApoB. Please read this carefully — especially if you're concerned about your LDL levels after "going keto."
– Coach Roxana
with @nicknorwitz, @realDaveFeldman, @DrRagnar, Venkat Manubolu, April Kinninger, @jayearls & @BudoffMd
(URL🔗 at the end of this 🔑)
Longitudinal CCTA-LMHR data is HERE!!!
And...
YES!!!
It's awesome!!!
But, first...
Those who know me, know, that the hill I'll die defending is "Mount Nuance."
I'm an internist. I'm physiologically incapable of making straightforward statements.
Don't take my word, ask @DGlaucomflecken about my kind.
If you expect to hear "X is Good" & "Y is Bad," well...
We've been accused of "spreading confusion." We aren't. We're simply showing that the ApoB story isn't as simple as we thought.
No, we didn't find LMHRs don't have plaque progression.
No, we didn't find anyone should stop their meds if they "Go Keto".
Remember that everyone's case is different, and two people who are treating the same disease with the same diet may benefit from very different advice.
Talk to your internist about YOUR case (😉).
Let's start with "that curiosity is the purest origin of Science".
Many times, people have said
"We thank the participants who made this research possible."
But this has never been more true!
This study was CROWD-FUNDED by a group of curious people!!!
But there's more!!!
In this study, 100 AMAZING humans LITERALLY bled (their fingertips) for a whole year so we could see these results!
And... Let's start there.
The ketogenic diet is THE ONLY ONE with adherence markers.
Every one-year-long diet study has to trust their participants' memory, and 🙏🏼 they're honest...
(I know... It's a BIG assumption).
Not here!
These 100 heroes proved with blood that they adhered to a diet like 👇🏼
All of them were lean, had no family history of CVD, and proved they had normal LDL-C before "going-Keto."
Please NOTE that, as a group, they are a low risk one.
However, some of them started their follow-up with intermediate/high CVD risk.
This will be VERY IMPORTANT later.
Now, there are many ways to assess coronary plaque and many different plaque metrics: Non-calcified, calcified, percent atheroma volume, grade of stenosis, total plaque score...
All are informative but imperfect.
There are many because all of them have different pros and cons.
We focused on
- Non-calcified because it changes quickly (but ignores size & location).
- Percent Atheroma Volume because it considers proportion of plaque vs. the🧡's size.
- Total Plaque Score because it considers both quantity and locations of plaque (but changes slowly).
If you look at TPS, that most stayed 🪒 (but remember TPS changes slowly).
If you look at NCPV or PAV, that many stayed 🪒. Some went ⬆️ & some ⬇️😮🤯
Sure, it was a minority (6/100), but ask most doctors if plaque REGRESSION with ⬆️ApoB is even possible!
SOME plaque progression is expected simply due to 🕓➡️🕒
Are LMHRs progressing faster than others?
No! They behave like other ⬇️CVDrisk groups.
More importantly, we see that NOT ALL LMHRs ARE THE SAME!!!
Those who started with ⬆️CVDrisk progressed faster.
All 100 participants have ⬆️LDL-C & ⬆️ApoB, but...
Are those with higher ApoB levels progressing faster?
In other words...
Are ApoB or LDL-C changes associated with plaque changes?
No ❌. They are not.
- Higher ApoB at baseline? No ❌
- Saturated Fat Intake? No ❌
- Adherence? (Maybe those not progressing were the not-so-adherent ones?) No ❌
- Age? No ❌
- Total LDL-C exposure? (On average, participants have been ~5 years restricting carbohydrates). No ❌
Follow-up is too short to see plaque changes!
This would have been problematic if we hadn't seen plaque changes at all... BUT WE DID!
The sample size is too small to see plaque changes!
This would have been problematic if we hadn't seen plaque changes...
BUT WE DID!
Lack of evidence of association between ApoB and plaque progression IS NOT evidence of NO association between ApoB and plaque progression!!!
...
Absence of evidence
≠
Evidence of Absence
...
In Stats, we don't accept hypotheses!!!
That is why we also used...
(They deserve their own 🔑)
In reality, Bayes was closer to being a Jedi, and the fathers of "Frequentism" were closer to being a gang of Siths. But that's a story for another day...
Wait for @alan_garfinkel's next 📖😉
Bayes Factors quantify (given the observed data) what is more likely? The hypothesis of "there is an association" (the alternative) or the hypothesis that "there isn't" (the null).
In our data, the null hypothesis was, consistently, 6 to 10X more likely than the alternative.
Can you imagine these results without adherence data?
How could we be sure we are not seeing associations simply because participants were not following the diet?
(Again, THANK YOU! to all those who made this research possible)
So...
What DOES predict progression?!?!?
🥁🥁🥁🥁...
How much plaque there was in the first place!
ALL baseline plaque metrics were associated with change in plaque after one year.
👇🏼here, you can also see how most participants started and stayed with low plaque levels (most dots are in the ⬇️ ⬅️ part of the plot).
But WAIT!!!
Maybe ⬆️ApoB did make things worse for those who started with ⬆️CVD risk!
I knew you'd ask!!!
Also NO ❌
When testing for this interaction, we found that, once again, ONLY plaque matters...
We shouldn't assume all people with an LMHR lipid triad have ⬇️CVD risk, and we shouldn't assume all people with high LDL/ApoB have or will have ⬆️CVD risk.
What should you do if your ApoB goes ⬆️ after "going keto"?
Talk to your internist!
Everyone is different (even among LMHRs).
My summer's project is to create free-to-access materials for clinicians assessing the CVDrisk of patients who are restricting carbohydrates.
This is the 🔗:
https://jacc.org/doi/10.1016/j.jacadv.2025.101686
Help us share it! 🔁🙏🏼
@bschermd @lowcarbGP @BenBikmanPhD @SBakerMD @DoctorTro @AKoutnik @EstebanDL @DrScottMurray @VivaLongevity @ChrisPalmerMD
As always 🤚🏼
Written by Dr. Adrian Soto-Mota MD PhD
Published April 12th, 2025
Twitter: @AdrianSotoMota
⚠️📢NEW PAPER📢⚠️@JACCJournals
— Adrian Soto-Mota (@AdrianSotoMota) April 7, 2025
with @nicknorwitz, @realDaveFeldman,@DrRagnar, Venkat Manubolu, April Kinninger, @jayearls &@BudoffMd
(URL🔗 at the end of this 🔑)
Longitudinal CCTA-LMHR data is HERE!!!
And...
YES!!!
It's awesome!!!
But, first... pic.twitter.com/Orx7XRW74f
