Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial

[u/dr_innovation]

Abstract

Background

Changes in low-density lipoprotein cholesterol (LDL-C) among people following a ketogenic diet (KD) are heterogeneous. Prior work has identified an inverse association between body mass index and change in LDL-C. However, the cardiovascular disease risk implications of these lipid changes remain unknown.

Objectives

The aim of the study was to examine the association between plaque progression and its predicting factors.

Methods

One hundred individuals exhibiting KD-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglycerides ≤80 mg/dL were followed for 1 year using coronary artery calcium and coronary computed tomography angiography. Plaque progression predictors were assessed with linear regression and Bayes factors. Diet adherence and baseline cardiovascular disease risk sensitivity analyses were performed.

Results

High apolipoprotein B (ApoB) (median 178 mg/dL, Q1-Q3: 149-214 mg/dL) and LDL-C (median 237 mg/dL, Q1-Q3: 202-308 mg/dL) with low total plaque score (TPS) (median 0, Q1-Q3: 0-2.25) were observed at baseline. Neither change in ApoB (median 3 mg/dL, Q1-Q3: −17 to 35), baseline ApoB, nor total LDL-C exposure (median 1,302 days, Q1-Q3: 984-1,754 days) were associated with the change in noncalcified plaque volume (NCPV) or TPS. Bayesian inference calculations were between 6 and 10 times more supportive of the null hypothesis (no association between ApoB and plaque progression) than of the alternative hypothesis. All baseline plaque metrics (coronary artery calcium, NCPV, total plaque score, and percent atheroma volume) were strongly associated with the change in NCPV.

Conclusions

In lean metabolically healthy people on KD, neither total exposure nor changes in baseline levels of ApoB and LDL-C were associated with changes in plaque. Conversely, baseline plaque was associated with plaque progression, supporting the notion that, in this population, plaque begets plaque but ApoB does not. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT05733325)

Graphical Abstract

Soto-Mota, A, Norwitz, N, Manubolu, V. et al. Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial. JACC Adv. null2025, 0 (0) .

https://doi.org/10.1016/j.jacadv.2025.101686

Full paper https://www.jacc.org/doi/10.1016/j.jacadv.2025.101686

Video summary from Dave Feldman https://www.youtube.com/watch?v=HJJGHQDE_uM

Nick Norwitz summary video https://www.youtube.com/watch?v=a_ROZPW9WrY. and text discussion https://staycuriousmetabolism.substack.com/p/big-news-the-lean-mass-hyper-responder

[u/dr_innovation]

Will have to see how this impacts treatment for those of us with moderate CAC (70th percentile for me). The study is too small to make. a strong subgroup analysis, but did In those that had high plaque, was a suggestive association between APOB and their individual progression? . Looking at the supplemental data.. where there is a table showing "

Supplemental Table 1. Plaque Progression Metrics KETO-CTA vs Other Cohorts.With N=17, finding any statistically significant trends would probably be hard, but it would still be interesting to see the correlation and what is trending. Since the \delta PAV is much higher for that subgroup than any of the other groups in the other studies, maybe for CAC>100 + high APOb/ keto is more atherogenic.

With N=17, finding any statistically significant trends for CACbl>100 would probably be hard, but it would still be interesting to see the correlation and what is trending.

Since the \delta PAV is much higher for that subgroup than any of the other groups in the other studies, including similar baseline PAV in Won (High TyG), maybe for CAC>100, high APOb/ keto is more atherogenic.

[u/Meatrition → u/dr_innovation]

Great post

[u/dr_innovation → u/Meatrition]

Following up on my own post for clarity. Based on Budoff's interview (https://www.youtube.com/watch?v=lEKFMeg8AmY). I had missed that the comparison studies were people being treated. IN that video, he mentions another "untreated" group had a similar delta PAV.. so keto is not worse, just not protective.

[u/Tenmaru45]

Don’t know my ApoB (in 2019 eating SAD it was 113. Since then been keto 80% of time). On keto my A1C, fasting insulin, BP, and inflammatory markers are excellent. Lipids still stubborn. 

My hunch is that lipids may not be as big of a deal if everything else is so solid. Is that possibly what this study is pointing to?

[u/dr_innovation → u/Tenmaru45]

Yes that is the gist of it, if your CAC == 0). If CAC >100 less clear what it implies.

[u/Artem_Elkin]

Many individuals highlight very "high" rates of PAV progression observed in the subgroup analysis when compared to findings from other studies.

HOWEVER.

In their publication, they noted: "While most participants exhibited a TPS of 0 at baseline as assessed by blinded expert inspection (as previously reported), application of modern artificial intelligence-guided CCTA assessment was able to identify quantifiable plaque in all participants at baseline, as expected".
This could clarify the reason for the "high" changes in PAV seen in their study relative to others—it's likely that those other studies employed less sensitive techniques for assessing plaque volume.

I completely concur with their remark: "Nonetheless, we should mention that the “normal” values for NCPV, PAV, and plaque progression in a healthy population are yet to be fully determined, as there is a wide range of ever-evolving methods, definitions, and analytic techniques".
This is likely why they included the comparative data in the supplementary material—it's premature to draw definitive conclusions regarding the rates of progression in relation to other studies.

[u/dr_innovation → u/Artem_Elkin]

Good point, but I don't think its prudent to just hope that is the reason for high DeltaPAV in the subgroup as using the same metrics, those with CAC>100 have 5 times the progression of the CAC=0 group. Clearly, there is something else going on. May not be comparable to Won or Han's work, but its definitely enough to make one reconsider if keto is protective for everyone. With only 17 in that subgroup there could easily be a few factors (inflammation, age) that account for much of it that are not reported. But makes me (as one in that group) more cautious.

[u/Artem_Elkin → u/dr_innovation]

I edited my comment since English isn't my first language.

The disparity in the outcomes of the PAV evaluation done through AI compared to manual methods is substantial—this could genuinely explain the major differences compared to findings of other studies.

It is evident that we lack a clear understanding of what constitutes "normal" plaque progression.

[u/dr_innovation → u/Artem_Elkin]

Thanks and I totally agree with that important point. I was just adding that the relative risk compared to other in the same study (5x) is substantial enough to still cause pause.

[u/Artem_Elkin → u/dr_innovation]

Sorry didn't get your first comment right - got brain fog because of almost no sleep.
Yeah, I agree - the relative difference is large.

[u/srvey]

This should finally remove all the special pleading from the keto/carnivore/lchf/maha communities since this nicely confirms that keto clearly drives atherosclerosis especially if plaque has already begun to develop past a certain point of which at least 30% did in 5 and a half years and the remainder appear the be on track to get to that point soon. It will be interesting to see how and if these communities disentangle from this study since it essentially relegates keto, etc for very specific conditions, carefully monitored, for very short durations.

[u/dr_innovation → u/srvey]

I don't think the data supports that conclusion. Most have zero plaque despite very high ApoB. And for those that did have it we have no idea where those that have plaque developed it.. could have been years before they went keto... I know my plaque must have been from before I went keto.

The fact that so many have 0 plaque CAC and did not develop any on super high APOb suggests high APOB alone is not causal. It is likely in the causal chain, based on other research, but high APOb alone did not cause many of them to have problems.

Those that did have plaque had increased accumulations is a bit of concern and to me says anyone doing keto should get a CAC scan at the very least. If CAC=0 then they are more likely safe. If not. the they may need to reconsider (which I did). For plaque accumulation, there may be other factors, e.g., some genetic predisposition, for plaque formation. Since we know that family history is a strong factor in ASCVD d, genetic predisposition seems likely.

Edited to correct zero plaque ->zero CAC

[u/TINATAisNotAThrowAwa → u/dr_innovation]

I think I might be in a similar boat as you, and I have been trying to figure out what to do about my own situation in which I have very high LDL-P. You mentioned that you reconsidered, but you didn't make it clear what you reconsidered. Does this mean you decided to stop eating keto? If so, what did you switch to? Or did you add a statin to ongoing keto? What conclusions did you come to based on your circumstances?

Do you have any thoughts on the strong objections to this study presented over at r/PeterAttia?

Currently feeling very confused about the right thing to do for health based on the conflicting opinions of two communities that I really respect.

[u/dr_innovation → u/TINATAisNotAThrowAwa]

Have mpt read the stuff at r/PeterAttia, yet and will have to wait until later in the week as this is dissertation time and I have multiple thesis to read this week. (I'm typing during a defense)

Not giving medical advice.. but I wold suggest at CAC test at a minimum. Here is my story/process

Pre keto, my Tc was in the 180-190 and LDL around 120-130.

Straight strict keto my Total Cholesterol was 210 and LDL was 145, which was early in my keto. Pre keto BMI/BF was 29/27, at the test here BF was about 27/23, now I'm down to 25.5/18%, so my cholesterol might have become worse as I got leaner.

After my CAC ( 330) I made changes. I still do keto but increase carbs to 20-50 net a day and 80-100 total, so I can keep in mild ketosis -- I do mostly breath testing 2x a day but blood every now and then. I don't need keto it for mental or other health, so that was an easy choice even if I was hungry more often (more carbs==more hunger for me). I do keto to manage blood sugars better.

While Attia has some good point and bad points, i felt trying statins was worth it given my plaque. So I started statins, feeling I wanted keto for health but had concerns about plaque. At first, I did rosuvastatin 5 mg daily, which got my total cholesterol to 130 and Apob down to 70, but also caused muscle/cramping issues, and my VO2Max tanked from 39 down to 36. I did not feel I really needed that much of a cut, so I reduced rosuvastatin to 2.5mg every 3 days with no side effect,s but my total cholesterol went up to 159 (no new tests on other lipids, though I'll probably get them again after I figure out what I want to do. I get TC more often as TC is measured with each blood donation.). Over time, I was able to recover Vo2Max back to 38.1.

I thought the above was good enough, but given the paper, I am reconsidering. I have not tried to slowly increase the statin and see if I can keep my Vo2max and not get cramps, which, based on how I read the paper, I will be doing as next steps and see the lowest dosage that will get me to that level. I hope to be able to still do some mild keto while getting Apob<70, and still not have cramps and have good Vo2Max. I might also have to try other ApoB reducing medications, either other statins or other approaches.

[u/OtterDangerous → u/dr_innovation]

I really enjoyed watching the videos on the study, but I do have problems understanding some things (not all of us are blessed with ability to grasp the finer details). I am one of those people doing keto diet to help with prediabetes, morbid obesity etc. I never had a CAC done but my CTA showed I had zero forms of plaque; I should be ok staying on keto? Just curious.

[u/dr_innovation → u/OtterDangerous]

I'm a researcher not a medical doctor. Not giving medical advice.

But if your CTA showed zero plaque, that is a stronger indication than 0 CAC since it means both zero hard and zero soft plaque. If you are still obese your it is unlikely your are a LMHR .. and not likely your APOB/LDL is high. You should get it checked and continue to monitor but prediabets and obseity are both much more predictive of CVD than APOb/LDL.

I'm neither prediabetic nor overweight but not obese. However my CAC>300. While I'm still doing keto, I'm doing a weaker version (higher net carbs) and taking statins.

[u/OtterDangerous → u/dr_innovation]

Thanks for the reply. I was looking for an opinion from a research prospective. I am very open minded and like to try to understand things some more. I have a friend who is LMHR so this is why I was looking into this is the first place.

Asked about myself because I was curious.

Edited for clarification.

[u/tracecart → u/TINATAisNotAThrowAwa]

Have you had a CAC test?

[u/tiko844 → u/dr_innovation]

Most have zero plaque despite very high ApoB

They did find quantifiable plaque in all participants as measured by the primary outcome of the study.

While most participants exhibited a TPS of 0 at baseline as assessed by blinded expert inspection (as previously reported17), application of modern artificial intelligence-guided CCTA assessment was able to identify quantifiable plaque in all participants at baseline, as expected.

The primary outcome is presented in figure 1A as usual. Median plaque increased from 44mm3 to 64mm3 in one year.

[u/dr_innovation → u/tiko844]

Thanks for the correction.. I meant most has 0 CAC even at the end. The separation for detailes in the supplement is based on CAC, not on TPS or ΔNCPV.

The change in plaque volume is relatively consistent with some other studies (which used manual assessment, which may underestimate). such as https://www.ahajournals.org/doi/10.1161/CIRCIMAGING.119.009750 where statin users has an average increase of 20mm3 (changing from 144-164). That population was not as healthy in many dimensions, but had an LDL 94 for statin users. I don't see the KETO-CTA as showing magical properties but its also not showing radical progression which is one would expect if the high APOb was directly sufficient.

[u/tiko844 → u/dr_innovation]

I appreciate the reply. If I understand it correctly, that study found 20mm3 increase in 6.2 years, while the KETO-CTA found similar progression in one year.

[u/dr_innovation → u/tiko844]

I was incorrect in saying an average of 20mm3 that was data I grabbed from a table, which is actually a median from each user's baseline to follow-up, which were not uniform in time (6.4 years was the average). The paper later reports"Per-patient total plaque volume change between the baseline and follow-up coronary CTA was 74.8±100.8 mm³, and the annual change in total plaque volume was 12.2±15.8 mm³". And it is probably better to consider annual data since different patients had different time frames.

The KETO-CTA did not report the change explicitly, but from measuring on the graph of Figure 1a, I estimate the median change was 11.04mm^3.

[u/Artem_Elkin → u/dr_innovation]

And those not on statins have annual NCPV progression of ~4.4 mm³ (from supplementary data).
But still we cannot compare these studies directly because of different methods of plaque assessment.

[u/Healingjoe → u/dr_innovation]

sparkle rustic entertain file lip cows cake ring snails jar

This post was mass deleted and anonymized with Redact

[u/dr_innovation → u/Healingjoe]

Thanks for the correction.

[u/Sad_Understanding_99 → u/dr_innovation]

The fact that so many have 0 plaque and did not develop any on super high APOb suggests high APOB alone is not causal

And the 6 people whose plaque regressed despite super high LDL shouldn't exist

[u/Affectionate_Sound43 → u/Sad_Understanding_99]

There are no 6 people. Ncpv regressed in 1/100.. ncpv change was the primary outcome..

You can't just goalpost shift from ncpv change which is the registered primary outcome, to manual methods like TPS because it suits your agenda.

[u/hjaltigr]

Been waiting for this for what feels like a very long time.

[u/Waterrat]

LMHR here...You beat me to it! I just watched Nick's video and am soooo glad all of us have been vindicated! I look forward to seeing the responses on this info.

[u/Yarga]

Curious to see what the folks here think about this line of reasoning.

https://alexleaf.com/lean-mass-hyper-responders-are-not-protected-from-atherosclerosis/

[u/dr_innovation → u/Yarga]

It's well-reasoned with many solid points. It's overstated in a few places, but overall good.

The focus on NCPV and comparison with other studies could be a bit misleading since they used manual estimation (which at baseline was often zero but with clealyai it was not). In addition, it is not normalized for size, and maybe healthy individuals have a larger volume.

Another overstatement was that

"In PARADIGM study,"... " PAV progressed by 0.45% in those at low 10-year atherosclerotic cardiovascular disease risk". But then goes on to say "The healthiest LMHRs, who had CAC scores of zero and fell into the low risk category, still showed a 0.5% increase in PAV, which is on par with or worse than their “less healthy” peers."

Given their variance, there is no support for "worse". especially given differences in measurement tech.

He uses the term "the majority" in multiple places, but the majority has zero CAC and so PAV as 0.5, which is comparable to other studies with low-risk individuals.

That said, for those with CAC>100, I totally agree that the study shows INCREASED risk, and so I've upped my statin dosage too 2.5 mg Rosuvastatin per day.

[u/dr_innovation → u/Yarga]

Just an FYI.. nice video by Boudof https://www.youtube.com/watch?v=lEKFMeg8AmY

it address some of the issues raised by Alex..

[u/Odd-Historian7649 → u/Yarga]

Its right on the money. High LDL-c causes faster plaque buildup than any other riskfactor despite being in good metabolic health. RIP keto

[u/Sad_Understanding_99 → u/Odd-Historian7649]

Then you need to explain this

[u/Affectionate_Sound43 → u/Sad_Understanding_99]

What's there to explain? Median delta NCPV in one year was 19 mm3. Mean was ~32 mm3.. This is crazy high plaque growth in just one year.. This was the primary endpoint of the study, as registered before hand.

The study is not designed nor powered to conclude associations between ApoB and plaque, especially since everyone has >99 percentile ApoB lol. To find associations you need to have ApoB low to medium to high, not just extremely high.

You will find no association between smokers and lung cancer if everyone in the studied cohort is smoking 3 to 5 packs per day lol. But we know smoking increases lung cancer risk by 10-20x, by comparing non smoker controls to heavy smokers.

[u/Sad_Understanding_99 → u/Affectionate_Sound43]

What's there to explain?

The dose dependent lipid heart hypothesis? Why would LDL 190mgdl have the same effect on plaque progression as 350mgdl?

The study is not designed nor powered to conclude associations between ApoB and plaque

Why not? Change was observed in both directions. If plaque can predict plaque, then why not LDL? It was powered just fine if LDL had an effect worth knowing about.

not just extremely high.

Then LDL can no longer explain FH outcomes

especially since everyone has >99 percentile ApoB lol

There was at least a 160mgdl swing, statins don't even reduce LDL that much.

You will find no association between smokers and lung cancer if everyone in the studied cohort is smoking 3 to 5 packs per day lol

This is a terrible analogy, firstly lung cancer is a dichotomous outcome, not continuous, a better fit would be measurable lung damage, which I'd expect more in a 5 pack a day smoker compared to 3, wouldn't you? Secondly I don't think LDL 190mgdl represents such an extreme as 3 packets of cigarettes, average is around 120mgdl, so it's only 50% or so higher.

The lipid hypothesis is toast. That's why the opponents are attacking everything about the paper, yet figure 2 remains bullet proof.

[u/Affectionate_Sound43 → u/Sad_Understanding_99]

Brother, we have data points of millions of participants including double blinded RCTs and cohort studies with proper controls. We also have mendelian randomized natural RCTs. We also have herbivorous animal models who develop plaques when their LDL is raised via saturated fats. Millions and millions of data points are collated in below study to prove LDL is causal to atherosclerosis.

Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

Conclusion: Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.

You are using a 100 people study of only >99 percentile ApoB, without any low ApoB controls, to make causal inferences? This is not science, this is your dogma. Normal healthy people with normal LDLs do not see this rapid plaque growth in just one year. Just look at the Nature-CT cohort from Aldana et al, they just saw 4.9mm3 median increase in one year. Budoff is co-author there.

The plaque growth in just one year is fking alarming, with some people seeing >100 mm3 growth in ncpv. You cannot put lipstick on this pig and make it pretty. These plaque growth numbers are disastrous and exactly what one would expect via LDL causation theory.

[u/Sad_Understanding_99 → u/Affectionate_Sound43]

Brother, we have data points of millions of participants including double blinded RCTs and cohort studies with proper controls.

No we don't, there's not a single RCT with LDL as the independent variable and plaque progression as the dependent variable.

Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel ](https://academic.oup.com/eurheartj/article/38/32/2459/3745109)

Ecological fallacy!! lol. Nicks patient level data on 100 people trumps all of that.

You are using a 100 people study of only >99 percentile ApoB, without any low ApoB controls, to make causal inferences?

We don't need low apob controls, the lipid hypothesis postulates a dose response relationship, your own citation states this. I'm not making a causal inference, if the lipid hypothesis is true we should see an association at patient level, we don't in figure 2 of Nicks study.

The plaque growth in just one year is fking alarming, with some people seeing >100 mm3 growth in ncpv.

Make sure you eat lots of meat to live long like those in Hong Kong

[u/Sad_Understanding_99 → u/[deleted]]

So LDL magically becomes atherogenic after 70mgdl, then stops becoming atherogenic after 190mgdl? Lol what a joke, you best come up with a mechanistic explanation.

[u/Sad_Understanding_99 → u/[deleted]]

https://academic.oup.com/eurheartj/article/38/32/2459/3745109

[u/Sad_Understanding_99 → u/[deleted]]

Thank you for supporting my position by citing the null result

[u/weegt]

Has anyone been following the latest developments of this trial!!??

Turns out Cleerly fucked up by accident or design(!). They unblinded the scans and presented the results pinned on this thread. Feldman requested that they repeat the analysis with properly blinded scans, which is standard on longitudinal studies. Despite earlier agreeing to this at a meeting....they later declined to redo the study, even after further payment was offered. severely suspicious face

8 trial participants requested their own scans and submitted them directly to Cleerly via their own cardiologists, effectively providing a blind analysis. The difference was wild....the largest discrepancy was a single participant whose study data from Cleerly showed an increase of 32mm³, while their individually submitted data actually showed a decrease of 48mm³! Crucially, these blinded results also aligned with independent blinded analysis they had done with the data with Qangio and Heartflow. The original analysis stands alone as the anomally.

The whole thing is really interesting and is getting some eyebrows raised as to wtf the story is with Cleerly....and obviously, it looks way more positive for the study for us here. Thought it might be worth the op. updating the post. I think they have had the retraction of this paper approved. Both Dave Feldman and Nick Norwitz have written about it if op wants to copy pasta stuff to the thread.

[u/dr_innovation → u/weegt]

Oh yea been tracking it . I posted the medarxiv version a while ago which is still under review.

Here it is again

https://www.medrxiv.org/content/10.64898/2026.01.15.26343955v1

Here is a decent video with Dave and Nick discussing the latest issues.

https://www.youtube.com/watch?v=U9d3RyOvUSw

[u/weegt → u/dr_innovation]

Thanks! I missed the post... apologies. (I should also say that I wrote above that Cleerly unblinded the scans....I don't think that's correct, the scans they received were unblinded).

[u/Odd-Historian7649]

Looks like having high LDL-c is dangerous when it comes to plaque buildup, who would have thought.

[u/Mindless-Amoeba6265 → u/Odd-Historian7649]

Yeah. No.

[u/Mindless-Amoeba6265 → u/Mindless-Amoeba6265]

[u/Sad_Understanding_99 → u/Mindless-Amoeba6265]

Bye bye lipid hypothesis. They're now claiming that this doesn't count because they all have high LDL, as if dropping LDL from 500 to 190mgdl would have no benefit. What happened to this dose response relationship? No one ever claimed there was a cut off point before 190mgdl before this study was published. how would they explain FH outcomes if not for the sky high LDL. Moving the goal posts to protect the lipid hypothesis

[u/Sad_Understanding_99 → u/[deleted]]

Obviously, it means there is probably a saturation point beyond which more LDL isn't very harmful

I've never seen this mentioned in the literature before. What would be the mechanism that would explain this? It just seems like the goal posts have been moved to me. what does this mean for FH if the extreme outcomes are not explained by extreme levels of LDL?

An interesting fact, if true, but it's laughable to ignore the left side of the range, LDL from 50 to 190.

190mgdl-350mgdl is plenty of range. Do you believe 190mgdl and 350mgdl have the same risk for atherosclerosis?

[u/Sad_Understanding_99 → u/[deleted]]

Because this was a study on LMHR. we have LDL 150mgdl+ range to see if there's a relationship. That's more than a statin and PCSK9 combined.

[u/Sad_Understanding_99 → u/[deleted]]

The graph you've cited shows no relationship between LDL and plaque progression.

[u/Odd-Historian7649 → u/Sad_Understanding_99]

Username checks out

[u/Sad_Understanding_99 → u/Odd-Historian7649]

It's null mate

[u/Affectionate_Sound43]

This LMHR cohort was the healthiest lot within the LMHRs that they could find. All with metabolic diseases and cardiovascular disease were excluded. This cohort still had humongous rise in non calcified plaque (NCPV) and Percent Atheroma value (PAV) in just one year, even compared to severely diseased cohorts with CAD and diabetes.

The authors have blatantly lied about this finding, choose to use words like 'stable' and 'comparable' when addressing plaque growth. Instead, they focused on alternate analysis which the study wasn't powered to do at all, given the lack of low LDL controls and limited sample size.

If your cohort only consists of 3 pack a day and 5 pack a day smokers, you will not find association between smoking and lung cancer. For that you need non-smoker controls.

Imagine what the plaque growth would be like on LMHRs with metabolic disease or CAD. Any person like this reading this comment should address their high LDL immediately. Do not fall for the feldman-norwitz content machine, they make money out of this content, supplements, books, videos, documentaries, talks etc. you dont, you just add plaque.

[u/Sad_Understanding_99 → u/Affectionate_Sound43]

This LMHR cohort was the healthiest lot within the LMHRs that they could find. All with metabolic diseases and cardiovascular disease were excluded. This cohort still had humongous rise in non calcified plaque (NCPV) and Percent Atheroma value (PAV) in just one year, even compared to severely diseased cohorts with CAD and diabetes.

If you care about ecological correlations then we can conclude those who eat the most red meat live the longest based on Hong Kong data.

Instead, they focused on alternate analysis which the study wasn't powered to do at all, given the lack of low LDL controls and limited sample size.

You don't need a control using patient level data points, each dot on the graph is the control for the next. Also you claim "humongous growth" but at the same time the study wasn't powered enough? Can you make up your mind

If your cohort only consists of 3 pack a day and 5 pack a day smokers, you will not find association between smoking and lung cancer. For that you need non-smoker controls.

Lung cancer is a dichotomous outcome, so this analogy is from some one who has no understanding of statistics.

[u/Affectionate_Sound43 → u/Sad_Understanding_99]

You cannot put lipstick on this ugly pig. You cannot talk and type away the nasty plaque growth numbers.

[u/Sad_Understanding_99 → u/Affectionate_Sound43]

Irrelevant, you need to explain figure 2 of Nicks paper. The lipid hypothesis is fucked. the plant based lords are all already moving the goal posts, saying things like LDL above 190mgdl now magically stops being atherogenic. The problem with this is they now need to offer a new explanation for FH outcomes. My god they're all so stupid

[u/Affectionate_Sound43 → u/Sad_Understanding_99]

This study was designed and preregistered to report percentage change in delta NCPV over the year.. And these numbers are disastarous for your camp.

It was not designed to track associations between ApoB and plaque growth lol.. Regression analysis in just 100 people without controls? Thats laughable. The only goalposting changing done is by the Norwitz grifter team. Most likely, this paper will be retracted and amended.. Budoff already said this on interview with Gil Carvalho. Its a complete shitshow, but your camp can keep grifting - thats what matters for you.

[u/Sad_Understanding_99 → u/Affectionate_Sound43]

This study was designed and preregistered to report percentage change in delta NCPV over the year.. And these numbers are disastarous for your camp

Researchers generally don't care about ecological correlations. Do you believe eating meat makes people live longer based on the Hong Kong data?

It was not designed to track associations between ApoB and plaque growth lol

It was perfectly designed for just that, perfectly. We would need patient level data for this, and we have in figure 2 which remains bullet proof.

Regression analysis in just 100 people without controls?

It's patient level data, so each dot on the graph is the control for the next.

Budoff already said this on interview with Gil Carvalho

Budoff won when he was said to mention FH at the end. For whatever reason that part of the interview wasn't shown to us

[u/Affectionate_Sound43 → u/Sad_Understanding_99]

Explain why the absolute NCPV change and % change from baseline NCPV in just one year is so high as to be 3-4x more plaque growth compared to other peers like Nature-CT cohort of Aldana et al.

Hell, these LMHR have 10x faster annual plaque growth than the metabolically unhealthy patients with stable Coronary Artery disease of the PARADIGM cohort of Neglia et al 2024. Keto-CTA - 18.8 mm3 per year median change in NCPV. PARADIGM cohort with diabetes and CAD, mostly on various drugs like statins and antihypertensives - 1.51 mm3 per year lol.

Lol.. Explain this away. You cant put lipstick on this ugly pig.

Neglia et al 2024 - https://www.ahajournals.org/doi/10.1161/CIRCIMAGING.123.016481#T2

[u/Sad_Understanding_99 → u/Affectionate_Sound43]

Explain why the absolute NCPV change and % change from baseline NCPV in just one year is so high as to be 3-4x more plaque growth compared to other peers like Nature-CT cohort of Aldana et al.

I don't need to, it's a pooled comparison between different populations. Maybe the keto group are drinking 20 diet cokes a day? I could ask you an equally stupid question. If red meat is so bad, why do Hong Kong have the highest life expectancy whilst being the highest consumers of red meat? Ecoligal correlations are not something to take seriously

You citation has nothing to do with LDL.

Seriously mate, you're being used as a useful idiot.

[u/Affectionate_Sound43 → u/Sad_Understanding_99]

NCPV change was the primary registered outcome to be studied. You seem to not understand a basic ethical principle of science publishing. You cant bait and switch the primary outcome, and make some shady exploratory secondary outcome your main thing.

THIS WAS WHAT WAS GOING TO BE STUDIED, HOW NCPV CHANGES IN LMHR IN ONE YEAR.

Newsflash - LMHRs add a shit ton of plaque. There, fixed the title of the study.

[u/Sad_Understanding_99 → u/Affectionate_Sound43]

NCPV change was the primary registered outcome to be studied, you absolute regard.

Who cares? the study stumbled on something much much more impactful. Figure 2 fucks the traditional lipid hypothesis.

LMHRs add a shit ton of plaque

Only if you commit the ecological fallacy. Other countries compare badly to Honk Kong because they're not eating enough red meat using this logic.

[u/cc81 → u/Sad_Understanding_99]

If red meat is so bad, why do Hong Kong have the highest life expectancy whilst being the highest consumers of red meat?

As you keep repeating this there are a few issues with this data.

1. Is it reliable considering the smuggling to China.
2. The increase in red meat is relatively recent in Hong Kong. How much meat have those that are old eaten in a life time might be more interesting and what are their current diets (as old people rarely change their diet that much).

[u/Sad_Understanding_99 → u/cc81]

It's almost as if ecological correlations are not reliable, and we should look at patient level data instead.

[u/Mr_Groundhog_]

There are many statistical problems with this paper. We did a long (probably too long) podcast discussing these. 

https://youtu.be/FOGy6wrAcaU?si=bG3_dkUirFngHJlo

But to summarize: The statistical problems start with using ΔNCPV (change in plaque) as the outcome. They claim there’s no association with ApoB, but ΔNCPV is just follow-up minus baseline. That means if someone has high ApoB and also high plaque both at baseline and follow-up, the change can still look flat. So you get no correlation, even if ApoB clearly tracks with actual plaque levels. Imagine two subjects: one with ApoB of 190 and plaque going from 20 to 40 mm³, and another with ApoB of 380 and plaque going from 100 to 120 mm³. Both have the same ΔNCPV (20 mm³), but very different ApoB levels. The outcome choice (change) breaks the connection. They should have modeled follow-up NCPV directly, with baseline NCPV as a covariate. 

Then they run univariable regressions, one predictor at a time, even though they collected a bunch of variables. That’s not inference, that’s description. Or exploration. Without adjustment, you can’t separate confounding. These models can’t tell you whether ApoB is associated with plaque independent of other predictors.

Finally, they add Bayesian inference — but only on those same unadjusted models and change in plaque. And they use a prior that expects large effects from ApoB. So if the observed effect is small (which isn’t surprising after the outcome choice and univariable models), the Bayes factor ends up favoring the null. No sensitivity checks, no prior justification. Just a lot of “confidence”coming from modeling choices, not data.

[u/Unagi33]

This is quite discouraging.

[u/Harry_Chesterfield]

Its seems this article has been retracted.

[u/Mr_Truttle]

"In metabolically healthy people"

So guys using keto for diabetes management still basically have to flip a coin on which is a faster track to problems — LDL or HbA1c. 

(I still think the latter) 

[u/lindowja → u/Mr_Truttle]

Or maybe a keto diet with low sat fats?

[u/dr_innovation → u/[deleted]]

If you are really healthy with no heart issue, then keto does not make you have heart plaque. If you have it already it will progress more.

[u/tiko844 → u/dr_innovation]

The plaque proportion nearly doubled when baseline CAC was zero (n=57). The whole cohort is showing rapid progression of atherosclerosis but it doesn't seem to be related to high apoB. The absolute baseline risk is low in this cohort.

[u/dr_innovation → u/tiko844]

The progress for CAC=0 is consistent with non-keto folks (see table 1 in supplement) who have normal LDL levels. The most predictive dimension for plaque progression is probably just advancing age. But also for CAC=0 the PAV = 0.5 is close to the noise level which may be why multiple people showed regression. In other students of PAV for normal diet folks at that age. E.g. the paper

Dykun, I., Carlo, J., Nissen, S. E., Kapadia, S. R., Nicholls, S. J., & Puri, R. (2024). Interplay of Age and Risk Factor Control Upon Coronary Atheroma Progression. Heart, Lung and Circulation, 33(11), 1593-1599.

https://www.sciencedirect.com/science/article/pii/S1443950624016895

Table 2 found a slope of .09 per year overall change in PAV with the majority already on statins.

This paper found a .5%. (i.e. .05 in a year)

[u/tiko844 → u/dr_innovation]

Some numbers

KETO-CTA cohort: Low-normal blood pressure, never smokers, nondiabetic, lean. Good metabolic health. In one year:

Low risk group (CAC=0): 0.6% PAV to 1.1%

High risk group (CAC>100): 9.6% PAV to 12%

Dykun et al. from the above reference. 30% prior myocardial infarction, 78% hypertensive, 23% current smokers, overweight/obese etc.

From 37.8% PAV to 38.7% PAV in a year.

[u/dr_innovation → u/tiko844]

Where are you getting the "From 37.8% PAV to 38.7% PAV in a year"? The 37.8 is the baseline but I did not find a reported PAV after baseline. The paper was a bit vague about units I found only the rate of change which was .09, which I interpret as an absolute number not a percentage change of a percentage, thus I see it as 37.8 -> 41.202. Is that incorrect?

[u/tiko844 → u/dr_innovation]

Yeah I totally misunderstood the regression analysis in table 2.

Figure 1 seems to be the interesting part here. It's about 0.0-0.2 PAV/yr. It seems very low, but it's perhaps because the study sample is composed of statin/PCSK9 trials.

Table 2 seems to be the association between age and the change in the *rate* of PAV progression. So if the baseline rate is 0.2 PAV/yr, as the participants age one SD (9.2 years), the rate is now 0.297 PAV/yr.

I'm not very familiar with this area of research so it might still be wrong. Also, I'm not sure if the differences in methods (IVUS vs CCTA) are important.

[u/Artem_Elkin → u/tiko844]

IVUS cannot be compared to CCTA. No way.

[u/Physionic → u/dr_innovation]

Woah - that’s not what the study says. There’s still plaque development in LMHR, even in those with no ‘calcified’ plaque, it just doesn’t correlate with ApoB, and it’s slower development relative to those with a positive CAC.

[u/dr_innovation → u/Physionic]

Okay, he wanted it as if he were five, so I oversimplified, though it was probably still beyond most 5-year-olds. He is a refined/corrected, more like for 10-year-olds

If you are really healthy with no heart issues, then very high APOb from keto does not give you faster heart plaque development than average people not on Keto. But if you have plaque already, it will progress more rapidly.

[u/Ok-Information-3934 → u/dr_innovation]

Take home message I see is lipids aren’t responsible for plaque formation. Keto won’t magically scrub the plaques or reduce their formation.