#2691

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

1 Like
#2692

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.

6 Likes
#2693

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.

1 Like
#2694

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

1 Like
#2695

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.

1 Like
#2696

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:

2 Likes
Sterols and Stanols for cholesterol reduction
#2697

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.

4 Likes
#2698

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.

3 Likes
#2699

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

2 Likes
#2700

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.

1 Like
#2701

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

#2702

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…

3 Likes
#2704

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?

#2706

@AnUser 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.

7 Likes
#2708

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.

#2709

I did try and debate you, but you are not tracking at all, making nonsensical responses like “that is what I said, ACM as a secondary endpoint”.

#2710

I am going to post this one last time. You can feel free to undermine the arguments in this study, if you do not address this study which I have referenced multiple times and told you to read, and babble on about how ACM is better marker and doesn’t cost much more or take much longer, then you are a dishonest actor.
You have to prove that it will not cost much more or take much longer, you base it on the calculations in this study to do so. Assume 50% will die from CVD from all deaths, in an equal time period as the study and the medication will prevent 15% of those CVD deaths, if you believe there is a more accurate number that is favored my way, then use those.

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.116.023359

#2711

OK - this discussion is getting to the point where it reminds me of this cartoon (XKCD is a very popular cartoon in the tech world. xkcd: Duty Calls …

Someone is wrong on internet-2

I mean - its a balance here, right. Its good to care about false information (especially here where we call care about longevity so much, so want to try to separate fact from fiction), but sometimes we’ve said our point and we just need to let it go.

@AnUser please, if you’re getting to the point where you’re really pissed off about a conversation, just take a break before you start personal attacks. I have a general policy, if I’m feeling fired up about some post… don’t post back immediately. Take a day off and revisit.

On another general topic I’d like to get people’s thoughts on. This thread has gotten a little long, as you likely have noted. Its a bit of a moderation nightmare… and I’m not sure how best to manage it. I’m thinking its time to “close” this thread , create a new one, and provide a link to the new one from here (and vise versa)… but I suspect few people are going to read this thread now from start to finish.

Your thoughts?

14 Likes
#2713

Close the thread. Too much bad feelings in it.

6 Likes
#2714

Ok, ill have another go.

“Goal post” isn’t a defined term, It’s a metaphor. It is obviously fine to use metaphors, but when you use them you kinda have to expect that other people may interpret them differently to how you meant them. I assumed “goal post” meant “a study end point”. So i pointed out that you had recently quoted an interesting study that had All Cause Mortality as a secondary endpoint. Obviously that study did run just a “bit longer” than the Fourier trial and came to a significant result for ACM without having to run for 50+ years (“25x longer”).

But… When you said “goal post” it now seems you specifically meant "primary end point only. Which seems a little odd given that we’d been debating whether the Fourier trial should have been terminated early (because the primary endpoint had been met) or allowed to run it’s course to investigate the emerging signal on ACM as a secondary endpoint.)

Now, to the “study” you quote above. And where i believe you’ve got things wrong

  1. It isn’t really a study, is it. It’s a discussion paper where they run some illustrative calculations.
  2. It’s referring to “primary end points” only, so isn’t directly relevant to our discussion about the Fourier trial.
  3. The part you’ve fixed on (“The 25x larger” example) Assumes that: “Suppose 3% of the target population will die over the next 15 years”. Whereas the trials we’ve been discussing (including Fourier) are all in elderly subjects with pre-existing cardiovascular disease. So this just simply doesn’t apply.
  4. If you read the papers, the death rate is much higher than “3% over 15 years”. And because they have preexisting cvd, the death rate from cvd as % of ACM is also much higher.
  5. As a sense check, think about the Fourier trial and how long it was due to run for … 3 and bit years. Now think about the interesting study you quoted which found a significant result for ACM in a similar population… it found that significance within … 3 and bit years. Not 25x that. Not 75 years. But … 3 and a bit