#497

I’ll be curious to hear what Dr Bart says, but it is my impression that Lp(a) just signifies a genetic predisposition to having heart disease. But you don’t need that to have risk. ?

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#498

Lp(a) is an independent risk factor, not the ONLY risk factor.
It’s similar to negative BRCA does not mean you cannot get breast cancer.

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#499

I assume you know the rough process of atherosclerosis, where damage to the artery wall occurs, then cholesterol is deposited, leading to cycles of inflammation, repair etc.

The ApoB and Lp(a) are like the major rate-limiting building blocks of the plaque. It’s safe to say that if you had 0 of both, it would be impossible to build plaque.

However, the overall rate of plaque generation depends on multiple factors. How much vascular damage occurs, how efficient your body is at cleaning up, how much chronic inflammation you have, how sticky those particles are etc etc.

So you can have people with low Lp(a) and APOB who still make plaque, because even the small amount of circulating cholesterol is enough to accumulate over time, and perhaps they’re very bad at removing it and cleaning up the artery wall. Then you get people with sky high cholesterols their entire life and zero plaque, because they’re somehow resistant to plaque accumulation.

The other interesting thing is that this is a function of time. So the longer you live, the greater accumulated damage. Studies have found that even children start to have fatty streaks in the artery wall, and most young adults have some form of plaque. Weirdly, humans are the only species where we accumulate plaque at “normal” (defined by population average) cholesterol levels. A perfectly “normal” reference range LDL-C of 80mg/dl is absolutely enough to build enough plaque to kill you early, and risk reductions occur all the way down to <20 mg/dl.

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#500

My mother has an LPa of 14 (borderline risk) an LDL of 68, Hs-Crp of 0.6 but triglycerides of 122. She had a heart attack, stroke and three stents at the same time. So low LDL and normal LPa does not mean you are not at risk.

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#501

Chris, what is your LP(a)? I have a measure of 17 on my LP(a) and while its a little high - I don’t think I need to worry too much about it. I’m doing everything I can on APOB, and its between 40 and 50, so I think I’m ok. My HS-CRP is at 0.26

#502

I haven’t measured my LPa yet. It’s on the list to be tested next. Same for my father. I’m hoping my father’s is low so that mine will be low as well. So right now, I don’t know.

My ApoB (48), triglycerides (65) and LDL (48) are low but my HS-CRP is 1.59. Not sure why it’s high-ish. Hoping to get all of them tested again this summer. I’ve also added some meds since the last test - Dutasteride and Galantamine. I wonder what effects they’ll have on my blood work.

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#503

He said apoB, not LDL-c.

You can’t have atherosclerosis with a low enough apoB for long enough. If your arteries are totally blocked from suboptimal apoB + other risk factors, and then you lower it, that’s not much of a help either.

LDL-C is an inaccurate estimate, and is even more likely to be inaccurate at higher trigs, it’s never actually measured, it’s just calculated with an equation like Friedewald.

If you really want to have some estimate of your mothers past risk check her historical data for HDL-C and total cholesterol, then measure non-HDL-C over the years (total cholesterol - hdl-c = non-HDL-c).

She had untreated diabetes too and probably other risk factors. If she didn’t want to do anything about that then she wouldn’t probably do anything about a suboptimal non-HDL-C or apoB either. But in most cases it would probably be too late either way what anyone did – had to start ~10-30 yrs ago.

Doctors many times don’t care enough or know to find the nuance like that LDL-c is inaccurate (especially at higher trigs), or look at historical data, or do it early enough, 10+yrs ago.

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#504

You are correct in that she, like many many others, waited too late to start preventing arteriosclerosis. Lowering ApoB is the best way to reduce risk.

That being said, I do believe that there are other factors that can lead to a heart attack such as triglycerides and/or a high HBA1C. Minimizing ApoB is excellent, but all factors must be included for total healthspan.

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#505

I don’t think you understood my point, those factors can’t cause a heart attack subsequent to a plaque rupture without apoB accumulation. Do you disagree with this point?

Total healthspan, of course, never disagree.

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#506

Of course you need ApoB accumulation. However, you can only reduce the amount of ApoB. You cannot eliminate it. As long as ApoB is present there is a chance for plaque formation which is probably where the other factors are influential. That’s my hypothesis.

The more ApoB you have, the greater the chance of plaque formation. However, if the other factors are really going the wrong way, you may need less ApoB present to form plaque.

I think we need to bring all the related factors into optimal zones - ApoB, HDL, triglycerides, LpA, HS-CRP and HBA1C. But I do agree that ApoB is probably the most important.

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#507

1st percentile (?) apoB is unlikely to do any plaque accumulation, at least better than higher amounts, around 30 mg/dl might be good. Other risk factors might become more important at higher levels then that.

Chance is wrong way to look at it in my view. At a certain level, it’s guaranteed to develop plaques dependent on time and with or without other risk factors. While another certain level the opposite, where that level is, who knows. Down to 30 mg/dl should have benefits.

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#508

I hope you’re right because I don’t want any plaque with my ApoB being between 48-68!!!

#509

I mean it will still be beneficial lowering to 30 mg/dl. So you are probably developing some plaque at your level, although much better than levels higher than that. It’s not so easy though without expensive meds like PCSK9 inhibitors, in addition to other therapies. For an upper normal lifespan, you’ve captured most of the benefit as long as your other factors are normal, if I’d guess. But it depends how much plaque you accumulated previously to starting when you did.

I’m obsessed about where the threshold is for no plaque accumulation. I don’t know where it is.

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#510

My pre Bempedoic Acid LDL number was 68, so quite low. Rapamycin took it up to 122. Bempedoic Acid and Ezetemibe brought ApoB; and LDL down to 68. 5 mg Atorvastatin brought ApoB down to 48. Muscle pain made me take Atorvastatin only Mon-Wed-Fri, so I’m probably at 58 now. Hard to go lower than that for me.

Hopefully a decade at this level will help me avoid arteriosclerosis at age 60.

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#511

First, sorry to hear about her situation and I hope she’s doing ok. I see your point, but to the best of our knowledge you really can’t build plaque without those lipoproteins. What matters is cumulative exposure, and obviously that increases with age. I would have to assume that her numbers weren’t always that good, or there were other risk factors, or she’s just extremely unlucky and susceptible to plaque formation. (On the contrary, there are people who have life long LDL-C of 200 and their arteries are totally clean in old age. For whatever reason, they’re resistant to forming plaque.)

The other risk factors (glucose, blood pressure, smoking etc) basically increase your susceptibility to atherosclerosis by increasing vascular damage and slowing down the lipid removal process.

The latest data I saw at a conference (from the Spanish authors of the PESA study) is that you seem to get ASCVD risk reduction all the way down to ApoB of 20 mg/dl

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#512

The latest data I saw at a conference (from the Spanish authors of the PESA study) is that you seem to get ASCVD risk reduction all the way down to ApoB of 20 mg/dl

I would love to drop my ApoB down to 30, but I’m already taking Bempedoic Acid, Ezetemibe and low-dose Atorvastatin (EOD). I think the next step is a PCSK9I, but I’m not sure how valuable that will be vs. my current situation. (It’s a price issue) However, do you think it is worth it in my situation? Or is there anything else that would work? @relaxedmeatball

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#513

As someone predicted here, discordant ApoB/LDL. ApoB 81, LDL 45. Fortunately Lp(a) negative. I’m not sure what the risk looks like for discordant ApoB, but I imagine with those numbers he’s likely to die of ASCVD (though likely much later than most, given his control of the other risk factors).

https://x.com/bryan_johnson/status/1897735712562462862?s=46

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#514

I asked about the apoB number almost two years ago, and it was possibly discordant all the time, this is not an expensive test. It was a mistake and it seems it was even higher.

That apoB is suboptimal with regards to plaque build up, at least 70 mg/dl is better, and we see in clinical trials lowering further LDL-C past the 5th percentile has benefits on MACE and plaque progression so most likely apoB even lower as most people are not discordant.

20-30 yrs or longer of suboptimal apoB is already probably a substantial amount of plaque build up which a CAC scan cannot detect.

CAC is a very late stage finding.

It doesn’t matter though if AGI and a few drugs will reverse atherosclerosis.

I hope his team does research this thoroughly

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#515

And now this… Bryan is building a religion. Not terribly surprised he wants to be a cult leader. Lol

Link: Anti-Ageing Millionaire Bryan Johnson Says He's "Building A Religion" To Save Human Race

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#516

And now the irony… as the “Don’t Die” religion’s leader - that eschews rapamycin.

As always the case… the cult leader send their entourage to an early end. Lol.

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