#1070

On the one hand I can understand that if you have no MACE at a given level of plaque, then staying at that level, stabilizing, and NOT continuing the progession/increase in plaque deposits, you will continue to have no MACE. Mission accomplished: no MACE at this level? Maintain this level and continue to have no MACE.

But on the other hand, MACE cannot be the only criterion of CV health. If you have significant arterial stenosis (or vascular stenosis in general), then your CV system is performing subpar, and in time, you may in fact experience MACE (no MACE up to now doesn’t mean no MACE in the future), or a slow decline into heart failure, because stenosis is accompanied by high BP, which over time can lead to such outcomes, even at the same level of plaque. Time alone is a factor when your blood flow is obstructed and your heart has to work harder to pump blood through, leading to cardiac hypertrophy, pressure on arterial walls, rupture and so on, even if the plaque level is steady.

So intuitively, I’d think plaque regression would be a desirable outcome, as it could lead to improvements in other parameters, such as BP. Unless of course the plaque levels are very low, so there is no significant vascular stenosis, then ok, keep at that low level and you should remain fine. But hey, I’m not a lipidologist and Dayspring is, so he’s probably right for reasons I don’t understand.

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#1071

I should read Dr. Lipid’s words a few dozen times more, but after just 4 times I believe perhaps he says that there is not such a consolidated model of plaque regression, nor a consolidated treatment, so we should presently stick to the ascertained facts. “Regression is not necessary”. It may be useful though, It may help to decrease risk, but in the accepted model presently it’s not being modeled.

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#1072

Makes sense. No doubt that very low levels of ldl-c will lower the cv risk and make you live longer, that said very low ldl-c may also increase your risk of dementia and who wants such a half-life?

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#1073

Conceptually, we know that the brain does not need high systemic LDL-C. In the period when the central nervous system has its booming development, from fetus to toddler, LDL-C has trivial values around 20-30 mg/dL. The brain is a formidable synthesizer of its own cholesterol.
The concern, if I understood well, is the potential detrimental effect of statins on the synthesis of cholesterol in the brain. But nobody really knows, it is left to individual perception, like muscle aches. Brain fog after statins suggests discontinuation. And yes, genetic predisposition for dementia might suggest a precautional strategy of non-adoption of statins.

As far as logic and scientific evidence suggest, the narrative to keep LDL-C/ApoB as low as reasonably possible is totally founded.
The focus of the research now should be to provide the safest means (drugs) to execute this strategy.

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#1074

The miracle threshold is apparently 5,000 mg/dL-years:

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If this model is correct, then to be below the threshold for 100 years, you have to always be under 50 mg/dL.

You can calculate your long-term risk with this exposure calculator: https://dir.nhlbi.nih.gov/OCD/MultiRiskCVD/

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#1075

That’s pretty low, it corresponds to 131 mmol/lt -years, a value which I’m going to reach in 3 years and it’s not even a pessimistic estimate… :cold_sweat:

By the way, cumulative exposure is very simple to calculate with a spreadsheet, you just draw a column for every year of life and for each single year you estimate, or report, your LDL-C in the same unit.

The sum of the values in the LDL-C column is the lifetime exposure.

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#1076

the 5000 mg/dL-year value is equal to the 1% cumulative risk value in the article by Ference et al., 2024, since this is the indicated (excess) lifetime risk at the value of 130 mmol/lt -years about equal to 5,000 mg/dL-years. This threshold in the UK biobank dataset is reached in men at 46 years of age (but their LDL-C values seem pretty high compared to other countries).

Again, this is a pretty low threshold, I wonder if it is too pessimistic, I’m going to listen to the video attentively

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#1077

Well, technically it’s possible to have a LDL below 10, just saying… If you stack all of the medications together and possibly have a very specific type of diet. PCSK9i + statin + ezetimibe + using canola oil instead of olive oil might be enough, and of course trying to decrease saturated fat as much as possible.

#1078

@AnUser If Kohsaka’s model is correct practically nuking LDL-C as you suggest wouldn’t be overkill. But again, it should be checked. If that’s true, after the age of 46 we should see an exponential rise in events in UK. Before taking such drastic measures I’m going to sit on the fence, meaning, I’m going to take less drastic measures…

By the way, I wasn’t able to find any relevant material from Dr Kohsaka

#1079

It’s not precisely harmful. Statin are well-tolerated, and PCSK9i and Ezetimibe even more so for most people. People do much more harmful things then that. I couldn’t find it but there was one who was pushing his LDL really low… he was above 70 yrs old.

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#1080

Low is good, but if there is a level below which there is no further plaque buildup or accumulation, then reaching that level should at least keep you from further deterioration, no? At least as far as atherosclerosis is concerned.

Of course if you want plaque regression, then you may need to hammer down with statins to the bare bottom.

But what of a case like mine, where I’ve had a life long very high LDL, HDL, TC, ApoB and very high Lp(a), and was unmedicated until I got on 10mg/day atorvastatin five years ago, but at age 65, had a CAC score of zero? Of course maybe I have soft plaque, but assuming someone doesn’t, then for such an individual getting to a level below LDL of 70 or so, presumably where no plaque will build, is there a point to going below that? FWIW, that is my plan, in addition to the atorvastatin I intend to add 180mg/day bempedoic acid and 10mg/day ezetimibe that will hopefully push my LDL from the current 133 to below 70 (I’d love a PCSK9i, but can’t afford it out of pocket).

Of course, there may be other benefits to lowering the LDL/ApoB levels, than plaque and vascular health (including cancer!), so, pushing far below plaque accumulation may make sense for other reasons.

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#1081

Your cumulative lifetime exposure would be pretty high at 60, but at least you avoided that it progressed further unchecked. To give a number to your excess lifetime risk you should have an idea of the values from birth to present day.

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#1082

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#1083

The argument that you have very high cholesterol and a CAC score of 0, so why do anything seems a lot like those who say they’re lifelong smokers and don’t have cancer.

It seems akin to playing Russian roulette. I prefer to take that last bullet out of the gun just to be on the safe side.

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#1084

To be clear, that’s not my argument. As I said, I Intend to drive my LDL below 70 at the least, and more if I could.

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#1085

You might want to take a look at the Danish study that I posted where the median age was 58. In the group with high LDL-C and zero CAC, I would say that 50 years is a long time to be winning at Russian roulette. It would suggest to me that there is a scientific explanation that hasn’t been clearly defined yet, not just “luck”.

Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL…

https://mmabrasil.localizer.co/t/the-ldl-kingpin-theory-one-ring-to-rule-them-all-lmhr/15982/6?u=ng0rge

#1086

there seems to be a compounding exponential type risk of heart disease and stroke with Apo B exposure. so 50 or 58 years may hardly tell us anything about what is needed to avoid risk in our 90s, 100s and hopefully beyond

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#1087

That may be, but it’s certainly enough to arouse my curiosity. If someone has gone untreated and shows a LDL-C greater than 190 mg/dL in their 50s and zero plaque, I would want to know how that could happen. The rules of lipidology say that ApoB is independently causal for plaque, both necessary and sufficient. So, how have these people, a small minority of the population but still a significant number, gone decades with high ApoB and zero plaque?

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#1088

@ng0rge

Interesting to study - yes

We as totality of data driven health optimizers and longevity seekers should take gambles based on that - does not seem smart

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#1089

Of course not, my interest here is not to drive recommendations or public policy but merely scientific curiosity at this point. However, I think that the scientific community is also starting to take a look at this (see my post from the Journal of Clinical Lipidology) and a better understanding as well as possible new therapies may come out of it.

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