心血管健康

[mccoy]

@AnUser

What would you give if someone would say they can prevent you from having heart disease? Sure, you might worry about an increase in PD risk, or risk of Alzheimer’s disease. But the trade off is total prevention of the primary cause of death. One is off the table, the other ones might have a small increase. Less things to worry about and optimize for, not to mention lethal and non-lethal strokes decreasing.

That is the rationale outlined by Peter Attia and I totally subscribe to it. However, what is meant exactly that CV risk (the first horseman of death) is off the table? I would construe that as risk=0, but that does not seem to be the case if we read the technical literature, at least the literature in discussion in this thread. The concept seems to be that the reduction in CV risk, if the interventions are not undertaken at the age of at least 40, are not of such a vast import as the words of Peter Attia would suggest. Even worse in my case, age 64, LDL at reasonable levels (70-90 g/dL).
A 40 mg reduction (30-50 mg/dL final value) would mean a relatively small 20% reduction in risk of MACE, after 30 years from the beginning of the interval.
That is something, but far from the glamorous result that I was expecting. I do not want to criticize Peter Attia either, but he is among else an engineer and applied mathematician and should be conscious of the quantity of the risk avoided, which would imply that CV risk is not really off the table (IF ‘off the table’=0 OR=negligible amounts).

[mccoy]

@Virilius

There are other studies showing plaque regression at a certain threshold. I’m assuming that is the point where risk drops towards zero over time.

We should discuss those studies as well, above all the numbers involved.

[adssx]

I don’t want to give medical advice but IF the cumulative exposure matters, then it works both ways and there might be compounding gains over time. I haven’t read this study but typically the OR are calculated over a follow-up period of about 5 years. So if there’s compounding then the theoretical 20% risk reduction you mentioned above would become a 60% risk reduction after 20 years (0.8^4) compared to someone (or the alternative “you”) who would not haven reduced their LDL by 40 mg/dL. If correct, that’s massive.

[adssx]

Here it is:

This chart does not mean anything other than a mathematical function that does 1.2x if you add 10 to the first argument and 1.4x if you add 5 to the other one. It was done by ChatGPT so there might be errors.

[AnUser]

You can’t develop atherosclerosis if your LDL is low enough, this is the case for those who have total abetalipoproteinemia (LDL = 0). They have a bunch of other problems because of the way the LDL is reduced, though.

The reason behind OR increase with age is because of LDL and time, not because of aging. So it’s dependent on LDL.

[Virilius]

There is some argument to be made that as we get older, LDL-C naturally increases while blood vessel cell walls weaken which necessitates an event stronger regiment.

[AnUser]

Well, that’s still LDL so, according to the eric topol interview I linked to earlier we will have more treatments soon so getting lower levels won’t be that difficult (and we will know more about safety to very low levels like near 0 that Eugene Braunwald aims for).

[adssx]

If obicetrapib is approved () then we might have a single pill atorvastatin + ezetimibe + obicetrapib giving a 90% reduction of LDL, ApoB, small LDL, and non-HDL while also lowering Lip(a) by 60%

[tj_long]

Yes, but what about those middle-aged people who may already have atherosclerosis, how reliably can it be generalized that atherosclerosis stops or even reverses if LDL drops really low? Of course, there are some indications of this in research, but many cardiologists are of the opinion that plaque cannot be removed… Of course, according to the current understanding, the best way is to drop LDL, as low as possible, but I wonder if that is enough if the “disease” is already too advanced. And this too is of course better in all scenarios than doing nothing.

[AnUser]

The one polypill to rule them all.

@tj_long

Yes, but what about those middle-aged people who may already have atherosclerosis, how reliably can it be generalized that atherosclerosis stops or even reverses if LDL drops really low?

I can’t give medical advice but you’re going to lower events and stabilize plaque, it won’t progress logically but still be at risk of events because of the plaque that is left, other treatments like optimal BP, inflammation and so on, become even more important as well to be included.

It’s not possible to reverse atherosclerosis, correct. It’s a part of the arterial wall. Lowering LDL a lot has some regression but it’s probably not clinically significant and reason for event reduction.

[Virilius]

@tj_long

but many cardiologists are of the opinion that plaque cannot be removed

There is good evidence that high intensity statin therapy, especially when combined with other therapies such as ezetimibe and PCSK9i, can cause significant plaque regression.
Intensive lipid lowering agents and coronary atherosclerosis: Insights from intravascular imaging - ScienceDirect

Extrapolating from those results, decades of statin therapy might cause all plaque to regress eventually.

@AnUser Seeing how studies consistedly show plaque regression, there must be some mechanism the body is using to get rid of soft plaque.

[adssx]

Yes plaque regression is possible: https://www.jacc.org/doi/10.1016/j.jacc.2021.10.035

[mccoy]

@adssx

I haven’t read this study but typically the OR are calculated over a follow-up period of about 5 years. So if there’s compounding then the theoretical 20% risk reduction you mentioned above would become a 60% risk reduction after 20 years (0.8^4) compared to someone (or the alternative “you”) who would not haven reduced their LDL by 40 mg/dL. If correct, that’s massive.

I read the whole study attentively (herein attached) and yes, as you say, the difference in relative risk (RR) is calculated over a 5 years timespan. In my own case, it would not be trivial to reach a -20% RR at 69. However, it is not clear to me how you scale the 5-years effect to a 10 or 30-years effect.

jamacardiology_sabatine_2018_oi_180035.pdf (457.7 KB)

[adssx]

@mccoy

However, it is not clear to me how you scale the 5-years effect to a 10 or 30-years effect.

We need the RR at 1y, 2y, 3y, 4y, 5y (or just check the survival curves if they’re provided?) and extrapolate the trend. At best if there’s pure compounding then it’s the square effect I mentioned above. At worst it’s a constant effect no matter how long. Reality is probably somewhere in between

[tj_long]

Yes, I’m aware of those studies, but on an individual level it’s hard to know in advance if it will apply. For clarity, I haven’t been diagnosed with atherosclerosis, although I haven’t been examined either. However, I have high Lp(a) as a risk factor, partly why I’m speculating about this. I intend to have a CAC scan within a few years and before that try to keep my LDL as low as I can with the medications my doctors are willing to prescribe. Currently Rosuvastatin 5mg and Ezetimibe. Although due to side effects (muscle pain and glucose rise) the doses are only 2.5mg Rosuvastatin every other day and 5mg Ezetimibe every day. However, LDL is quite low at 58mg/dl.

[RapAdmin]

Cool video of how blockage forms in an artery: A buildup of fatty deposits (plaque) in the artery wall can eventually rupture, triggering a series of events where blood clots form. This can completely block a coronary artery, leading to a heart attack.

See Here: x.com

[Neo]

@tj_long

Although due to side effects (muscle pain and glucose rise) the doses are only 2.5mg Rosuvastatin every other day and 5mg Ezetimibe every day.

Do you have side effects from Ezetimibe?

Many here also use bempedoic acid - see eg @DeStrider experience

[tj_long]

Yes, fasting blood sugar rises. Bempedoic acid is not yet available in the country where I live. Ordering medicines from outside the EU is a crime here, as is ordering without a prescription.

[adssx]

I don’t know where you live but you can get prescriptions for anything here: https://eudoctor.org

It’s valid across the EU. And then I’m sure you can find an EU pharmacy to send it to you.

[mccoy]

@tj_long

Yes, fasting blood sugar rises. Bembedoic acid is not yet available in the country where I live. Ordering medicines from outside the EU is a crime here, as is ordering without a prescription.

I live in Europe (Italy) and here bempedoic acid has been available for a while, you may want to make sure, if it’s legal here, then it’s approved by EMA hence a legal drug elsewhere in the EU.