Thanks for all the engagement, let’s see if I can clarify.
The 50% reduction would be a lifetime reduction for people starting in their 20s and 30s with no obvious risk factors.
The 50% number has been pulled out of thin air, but a number that seems plausible to me. When I say plausible, I mean that given what I have read so far, it wouldn’t surprise me if that was the case.
There is indirect evidence based on the PCSK9 genetic mutation, but like you said, this doesn’t guarantee that you would achieve the same results by lowering LDL-C artificially. But, it does make it more plausible.
Mechanistically, it also seems plausible to me, because plaque accumulation happens over the span of 4 decades.
Your meta analysis doesn’t push back on this number, because it does an analysis over a relatively short treatment period. Its selection criteria are a treatment period of at least one year and a follow-up of six months. As far as I’m aware there doesn’t exist a trial with a 10-year period or longer. What I’m discussing here, when I say the 50% number, is a 60 year treatment period.
I wish I could give a number for lifetime treatment of atherosclerosis in a population with no obvious risk factors, because that is exactly what I’m looking for!
The 50% is just a guess that I tried to made plausible in the previous parts. This is also why I wrote this article, to discuss if this guess is correct.
To me it seems plausible that a mild reduction in your LDL-C/apoB during your whole life will have a lot of impact, because the disease takes 4 decades to develop. Current treatment strategies treat very aggressively, but only in the last decade. At which point you have already collected 3 decades worth of plaque.
This study I highlighted also seems to point into that direction.