Atherosclerosis Root Cause Diagram with References

I drafted out the above Root Cause Diagram to pictorially represent a personal view of Atherosclerosis, and perhaps help with the discussion; there are copious references for all causal links shown [SCROLL TO BOTTOM FOR GROWING LIST] - I'll reference them as time goes on and people add to my bulging archive.

Definition of Root Cause (RC)

"Following an excursion, Root Cause is the interplay between (A) The most direct mechanistic driver(s) of the issue (usually situated early  in the root cause chain diagram), and (B) the most addressable factor(s) to achieve acceptable solution (usually it will be the factor that has actually shifted and precipitated the excursion)".  There may be multiple coincident factors that are implicated as worthy of Root Cause status btw - especially in the nasty issues, and this is certainly one of those.

Which brings us to our Atherosclerosis/CVD "Excursion" in the past century. This is certainly a multi-causal and highly interactive problem, no one would argue with that. Simplified, there are broadly two schools of thought:

(1) The truest RC is so-called "Cholesterol", with it's causal influence best measured as the number of APoB 100 containing Lipoproteins (i.e. ApoB or LDL-P).   I agree that this is a critical factor influencing the disease, and it can be influenced downwards if needed which will certainly mitigate the progression. In short, the first part of RC (A) is met.  Now to part (B) - is it the factor that has changed to precipitate the problem, and is it the most addressable? Well, it has certainly changed with the modern diet, and this can be addressed very well in most cases, and drugs too, so it is a good RC factor for sure. The philosophical challenge is whether it is inherently the true addressable root cause that has changed, in and of itself, and whether drugs are the true solution (after all, no-one is suggesting that the problem occurred because previous historical drug use was discontinued for a while, right?

(2) The truest RC is excess Sugar/Carb, driving a catastrophic milieu of dysfunction, and when this is resolved then the ApoB reverts to being non-significant in the scheme of things. This would fit both (A) and (B) quite acceptably.  Of course there are other things to address (e.g. 25(OH)D Deficiency, w6/w3 balance, Smoking, Exercise etc etc, but let's focus on the Primaries).

This post wouldn't be complete without the Quebec study (sub group of NON-Diabetics, so most interesting):

The growing references list:

VITAMIN D DEFICIENCY  Relation of Vitamin D Deficiency to Cardiovascular Risk

GGT: GGT  reference and full library:

FERRITIN: Ferritin ref, Ferritin Recent FeAST Trial, and Ferritin Library:

NITROUS OXIDE: BP / Ox Plaque Ref from @Mommy_md:   Triggering Oxidative Stress...  

NEOVASCULARIZATION: Vladimir's excellent, alternative (and correct?) mechanism for Atherosclerosis LDL ingress:

AGE's and RAGE's:  from @iainlane88:

W6/W3 Ratio:  From the Cholesterol Hypothesis to w6/w3 Balance - great book