Eli_

[Question] Should I buy a Fair­phone or a re­fur­bished iPhone?

• Eli_ 30 Nov 2022 12:47 UTC

  3 points

  1 ∶ 0

  in reply to: Henry Howard’s comment on: Prevent­ing atheroscle­ro­sis, the eas­iest way to im­prove your life ex­pec­tancy?

  I agree that lifestyle changes are hard to do, but I would like to push back in two ways:

  • Currently, it isn’t standard practice to measure apoB and base treatment on that statistic. This would result in doctors prescribing medication to people that are at risk, but that are currently unaware.

  We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy.

  • Furthermore, there is the option of early treatment with medication, that currently isn’t deployed. Like I described in the article, you can have a lifetime risk of 39-70% while also having a 10-year risk <10%, which means you won’t get treatment. While it is seems plausible that these people would benefit a lot by this.

  To summarize it bluntly, it seems that the world would benefit from prescribing more cholesterol lowering medication. Advocacy for doing this would be the cost-effective solution.

  Having said that, I didn’t start writing this article while having EA in mind. So I haven’t done an intensive cost/​benefit analysis.

• Eli_ 30 Nov 2022 12:39 UTC

  1 point

  1 ∶ 0

  in reply to: bruce’s comment on: Prevent­ing atheroscle­ro­sis, the eas­iest way to im­prove your life ex­pec­tancy?

  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!

• Eli_ 30 Nov 2022 8:30 UTC

  1 point

  0 ∶ 0

  in reply to: bruce’s comment on: Prevent­ing atheroscle­ro­sis, the eas­iest way to im­prove your life ex­pec­tancy?

  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.

  For instance, a paper from 2006 called, Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease, looks at the presence of mutations in a gene called PCSK9 which is associated with a lowered LDL-C and apoB. Black participants had a 28 percent reduction in mean LDL-C and an 88 percent reduction in the risk of coronary heart disease^[6]. White participants had a 15 percent reduction in LDL-C and a 47 percent reduction in the risk of coronary heart disease.

Prevent­ing atheroscle­ro­sis, the eas­iest way to im­prove your life ex­pec­tancy?