Rapamycin and risk of cardiovascular disease

@LaraPo My apoB is 48 down from 73 1.5 years ago.

My apob stack

  • rosu 5mg x 2 every other day (to avoid weight lifting days). I’ve started reducing to 5mg every other day since my apoB is so low.
  • ezetimibe 10mg daily. I skip rapa day.
  • niacin 500mg alternating days with nicotinamide 500 mg. I skip rapa day.
  • vitamin b5 500mg daily. I skip rapa day.
  • fish oil daily
  • high fiber diet

I also aggressively manage blood sugar (HbA1c now at 5.5 down from 5.8 6 mos ago). I don’t know if that affects apoB but I believe it affects ASCVD.

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Yes. Atorvastatin bothered me much more than rosuvastatin. I switched a year ago.

That’s pretty impressive from rosuvastatin eod. Is the drop from 73 to 48 primarily ftom the rosuva + ezetimibe? I.e. were you already high fibre, omega 3 and high exercise etc?

Out of curiosity what’s your blood pressure?

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Changes included

  • rosu & eze
  • vit b5
  • higher fiber; stopped dairy (was only nonfat)
  • less cardio exercise (due to knee pain which has now subsided; don’t know what caused it or stopped it)
  • stopped alcohol (1-3 drinks / year)
  • rapamycin
  • metformin
  • started / stopped LDN

BP has always been good: today was 100/61.
RHR was 41 this AM in a sitting position.

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BP of 100/61 + 48 ApoB = eternal life?

That’s very impressive. How do you feel since starting the new regimen?

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Cancer and the heat death of the universe can still get him.

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I feel great when recovered from rapa and/or workouts. The combination of stress from: work, exercise (5-7 hours cardio + 3 hours weights per week), and rapa is a bit too much when all 3 are together. I am moving to a 2 week rapa cycle. Once I get my sleep working consistently I can get more aggressive (again) with rapa.

My latest effort is in HRV biofeedback. It’s going very well with an amazingly fast rate of improvement. I’m optimistic.

I’m interviewing Marco Altini of hrv4training soon to take a deep dive into HRV as a tool for stress mgmt vs training mgmt. I’m now using eliteHRV and hrv4biofeedback apps on my phone.

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Mostly heard about it from Peter Attia’s podcast guests and then asked my cardiologist about and felt that he shared the view. Basically you see the low PSCK9 people doing well in general and the high PSCK9 people do poorly

Here is some of the history:

The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is interesting. Nabil Seidah, a researcher in Montreal, Canada, identified PCSK9 encoded by a gene on chromosome 1.[1] Collaborating with a French group, they found out that a gain-of-function mutation in that gene was responsible for familial hypercholesterolemia in a French family. This was followed by similar findings from other researchers.[2]

In contrast, findings from the Dallas Heart Study showed that loss-of-function mutations in PCSK9 gene were associated with very low cholesterol levels and markedly reduced incidence of CVD.[3]

  1. Elguindy A, Yacoub MH. The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research. Glob Cardiol Sci Pract. 2013;2013:343–7. [PMC free article] [PubMed] [Google Scholar]

  2. Leren TP. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin Genet. 2004;65:419–22. [PubMed] [Google Scholar]

  3. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005;37:161–5. [PubMed] [Google Scholar]

You can probably find more info about people with genetically lower PCSK9 through doing a lit search.

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if one were to start using one of those which would you suggest?

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Elite HRV is free but harder to figure out what to do. Hrv4biofeedback is $10 onetime fee on apple but is super easy to start using. It even helps you figure out your personal resonance breathing rate which I couldn’t do on my own. It’s a pick ‘em.

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Do you know if you are more an overproducer or absorber? That helps guy part of my decision making.

Abnormalities in cholesterol metabolism have been associated with patient response to statin and ezetimibe therapy for LDL cholesterol (LDL-C) lowering.

https://bostonheartdiagnostics.com/test/boston-heart-cholesterol-balance-test/

Can now be done from home in a cheaper way, here:

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I get angry at people saying false things that will get people killed. It’s ok to do so about flat earth, but not about this. Cardiovascular disease people have to be careful what they say IMO as it’s the only disease that can be prevented and treated well, and not think out loud. That is why this thread is my nemesis.

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I think the original dispute was not about lowering apoB per se (disregarding the usual suspects of course) but about PCSK9i and their effect on all-cause mortality.

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If CAC = 0 then LDL levels aren’t predictive of cardio event. See below.
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061010

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Depend on the time period you are predicting over.

If you care about many decades or probably just about several decades it almost certainly does - and in a major way.

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Haven’t read the paper, but from a skim your conclusion seems like it may way off if this is the actual time period the paper looked at?

During a median follow-up of 4.3 years

It’s also potentially dangerous to misrepresent the research on targeting extremely low cholesterol. Especially when you haven’t read some of the research you have such strong opinions on. Shouting people down with abuse is never really justified even when you’re right. But when you’ve not really read the research…

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You’re still angry? You’ve now accused me of being a “tinfoil-hat-wearing conspiracy theorist artist with Autism/Asperger’s and reading comprehension issues”. All because I tried to give balance to the discussion of the Fourier trial by quoting from a BMJ paper reviewing it.

You’ve also accused the scientists who independently reviewed the Fourier trial of being “rogue doctors” who didn’t bother with blinding. Is this a big issue for you, or do you just like throwing around insults anonymously online? Why not take a longer break fro the board?

@A_User after having seen this whole tread unfold I have to say that I do think you have sometimes said things in non constructive way that does not fit with the community that @RapAdmin has built. Your comment above about autism/asbergers is one example.

Let’s please be more constructive - we are all on this journey together.

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Except I’m not making anything up. You hadn’t “really read” the BMJ research paper you had such strong opinions about. That was pretty obvious from what you posted about it. Remember , there’s quite a big difference between “really reading” a paper and “I probably did look at it”.

If you don’t want to engage, maybe stop posting abuse? There’s an interesting debate to be had if you can manage to accept that people might try to contradict your views. This board just isn’t really the place for playground stuff.