Thread by @DaveKeto

1/ #ListeningThread

Looking forward to hearing this one re #LDL #Cholesterol #CVD

https://twitter.com/NutritionDanny/status/1376872351661498369

2/ I love that Alan Flanagan kicked off with distinction question re bio markers.

“System Biomarkers in the causal pathway. Systemic biomarkers that can report on the overall picture”
vs
“Biomarkers of disease progression”
...

3/ “... It seems to be in the wider conversation a lot of these are often conflated to a degree. Or there is misplaced emphasis placed on a particular marker...”

I couldn’t possibly agree with this more!

4/ further props to Alan, he asks about some “niche” circles who propose high LDL is not a concern where inflammation is low or endothelial health is optimal...

5/ Prof Chris Packard “The answers lie in looking at the data. And some of the natural experiments that we have support the idea that LDL is causal. And prime among those is familial hyper cholesterolemia.”

6/ he then goes on to describe how heterozygous FH (2-3 fold) results in elevated CVD), homozygous FH (>3 fold, often 5-fold and higher) resulting in corresponding increase in atherosclerosis. HoFH children exhibit signs very early (heartbreaking).

7/ “These individuals don’t have raised CRP, they have raised LDL...”

“ if you are unfortunate enough to [be born with homozygous FH], then that youngster will develop severe atherosclerosis early in life, by age 8, if not 10 and 11.:.”

8/ “...and often they used to die of coronary artery disease purely on the basis of a raised LDL in their teen years.”

“So that is prima facie evidence that LDL is it causal agent.”

9/ So I'm going to pause here to really discuss this crucial point, as I bring it up very frequently when discussing #LMHRs and why this study is so important.

It's understandable why FH is crucial to looking at LDL in the context of other CVD risk markers being normal/optimal..

10/ If it is true that the atherogenicity of familial hypercholesterolemia is entirely in LDL/ApoB concentration, this would be very substantial evidence toward the lipid hypothesis and would definitely be demonstrated in progression observed with #LMHRs

11/ Again, I hope this is not the case, but it's all the more reason we should be capturing this data as soon as possible.

I credit both @NutritionDanny and Alan Flanagan for their consistency in predicting the #LMHRstudy will show rapid progression of atherosclerosis...

12/ ... And again -- with emphasis -- while I'm cautiously optimistic, I genuinely don't know what the data will bring us until it is coming in from the study.