Atherosclerosis - Plaque in Arteries
Why should I be concerned about Atherosclerosis?
When I was diagnosed with Diabetes, I dug into it pretty hard core. I wish that I had done it much earlier in life and I also wish I had documented what I found in a more complete way. Regardless- here I am now...
The more I looked into Diabetes, the more clear it became that CardioVascular Disease (CVD) was the *real* health problem that I should be concerned with.
Those people with Diabetes are at much higher risk of a CardioVascular Event (CVE). That was my tie-in to dig deeper into CVD because it seemed everywhere I looked- the #1 'complication' of Diabetes was CVEs.
That was all I needed to add CVD to my 'list'.
I accepted that, in essence, Diabetes = CVD
(Yes, there's more to Diabetes, but for this discussion I am simply showing the path I followed)
Pulling the 'string' on CVD I find references to CardioVascular Events (CVE) being discussed as an overall umbrella covering many different 'heart problems' but the main concern seems to be Atherosclerosis.
Having made the connection that Diabetes ~ CVD ~ Atherosclerosis, I started to dig into what it is, what causes it, and what one might do about it.
What, exactly, is Atherosclerosis?
Let's first go through some discussion on the definition of Atherosclerosis.
The National Heart, Lung, and Blood Institute has a pretty good discussion of 'What Is Atherosclerosis' and expands the discussion to include Coronary Artery Disease (CAD), Peripheral Artery Disease (PAD), and a few others.
I ask you to have a look, while there, see if you can find any mention of 'veins' (as opposed to 'arteries') go here:
https://www.nhlbi.nih.gov/health/atherosclerosis
For some 'light reading' head on over to ScienceDirect which gathers what several publications have to say about Atherosclerosis in one place.
https://www.sciencedirect.com/topics/medicine-and-dentistry/atherosclerosis
What some others have to say:
Johns Hopkins Medicine
American Heart Association
NHS (UK's biggest official health website)
My understanding reduces the complex medical terminology into this:
Atherosclerosis = thickening of of artery walls due to plaque build up.
Two key points-
- It is all about a plaque being started and grown
- Every definition I find seems to say 'arteries' and not 'veins'
So, what causes a 'plaque' to form?
Spoiler Alert- there's good recent papers that present a very plausible explanation for why a plaque might start and grow. I will get to that later, first- I think we should go through the 'legacy' or 'mainstream' explanation(s) so that we can get a clear contrasting picture.
It all started with the Diet-Heart Hypothesis
More or less, the Diet-Heart Hypothesis states that eating saturated fats causes those fats to get into, and eventually clog, the arteries.
There is plenty of controversy surrounding this subject and I, for one, feel like this is a huge example of 'error carried forward'- which I will explain in a moment.
In the mid-1900's, The conclusion was dietary fat/cholesterol clogged arteries.
The Seven Country Study was a major influence...
Dr. Ancil Keys - The Key Architect
Somehow, some way, a leap was made...
Autopsies of CVD victims showed fat/cholesterol build up in the arteries- and the leap- therefore dietary fat/cholesterol causes CVD.
Error Carried Forward Begins...
It appears to me that at first, there was no 'plausible mechanism' other than 'cholesterol in the blood is sticky and gums up/clogs the arteries'.
Who knows, but it seems that was 'plausible' enough for many researchers who went on to design research and studies to prove Diet-Heart (Lipid-Heart) hypothesis.
The Critical Error- No Plausible Mechanism
To me, there is a critical error in the plausibility of the 'mechanism' offered- namely, that high cholesterol in blood 'clogs' the arteries.
First, remember back when I asked about why is Atherosclerosis namely in the arteries but not in the veins? Well, that was because of this- Arteries are the 'high pressure/high flow' pipes while the veins are the 'low pressure/low flow' pipes in the blood stream...
If high cholesterol 'clogs' the pipes, why is the clogging seemingly concentrated in the 'high pressure/high flow' pipes (like the sink faucet) and NOT in the 'low pressure/low flow' pipes (like the sink drain)?
The answer is blisteringly simple- Atherosclerosis doesn't primarily affect the veins because 'clogging' due to 'stickiness' is not the mechanism. If it were, the small capillaries where blood flow was slowest would 'clog up' first...
What followed was 'good science' based on a bad foundation
A hyper-focus began to develop on cholesterol in the body and its association with CVD. At some point the 'low density lipoprotein (LDL)-cholesterol hypothesis, stating that a raised LDL level *causes* thickenings within arterial walls which gradually develop into larger plaques.
"Good" (HDL) and "Bad" (LDL) cholesterol became the prevailing thesis- and lowering LDL was the goal.
Seemingly every study seemed to come back with the same result: LDL concentration in the blood was ASSOCIATED with higher CVE's and CVD mortality.
Still- no plausible mechanism was offered.
A mechanism was offered but, certainly not plausible...
"LDL-C (Bad Cholesterol) penetrates the artery walls, High blood levels of the 'bad' LDL-C makes that process go faster"
Which if so, again, why only in the arteries and not veins? If the 'cause' is LDL-C migrating from areas of high concentration to areas of low concentration- then would it not stand to reason that this would happen *anywhere* there was such a concentration gradient?
This simply doesn't answer why Atherosclerosis doesn't seem to concentrate in the low pressure/low flow veins (or universally across all 'blood pipes').
None-the-less, there IS an aparent association between LDL-C and CVD
At this point, there is an overwhelming 'consensus' that since LDL-C blood concentrations are correlated so 'strongly' that the only conclusion is LDL-C *causes* plaques to form.Â
It is fascinating to me that not one of these studies shows a plausible mechanism where by High LDL-C concentrations, ON ITS OWN, *causes* a plaque to form...
- Mihaylova B, Emberson J, Blackwell L, et al. Cholesterol Treatment Trialists (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380:581–590.
- Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372:2387–2397.
- Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372:1489–1499.
- Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372:1500–1509.
- Hegele RA, Gidding SS, Ginsberg HN, et al. Nonstatin low-density lipoprotein—lowering therapy and cardiovascular risk reduction—statement from ATVB Council. Arterioscler Thromb Vasc Biol 2015; 35:2269–2280.
- Williams KJ, Tabas I, Fisher EA. How an artery heals. Circ Res 2015; 117:909–913.
My Request To You...
At this point, I'd like to ask you- If you are aware of any paper or publication that details the actual mechanical, chemical, hormonal, or physical mechanism where LDL-C, in high concentrations- and on its own, *causes* CVD...
Please share it.Â
A quick recap
As of today, there is a large community that believes LDL-C *causes* plaques to form and that reducing LDL concentration in the blood provably lowers CVD risk and CVE frequency.
Stemming from this is the broad guidelines for using statins to lower the 'bad' LDL-C in the blood.
Note: I've reduced this discussion of cholesterol to a very narrow point of LDL-C and have not included discussions about HDL-C, Triglycerides, the various sub-components within the umbrella term 'LDL-C', remnant cholesterol, the ratios between various lipids on purpose...
The point isn't to find 'relationships' or 'correlations' between various lipids and CVD.
The point is to find a 'PLAUSIBLE MECHANISM' (which there has been none so far that I can find where LDL-C *causes* plaques to form).
Well, if it isn't 'high LDL' then what is it?
That's a great question, it is the one I've been trying to find in the papers, studies, and publications... And, it turns out- there's some very robust information out there...
A new mental model- a 'plausible mechanism'
Bottom Line Up Front (BLUF):
A plaque is the result of the healing process for an injury to the interior of a blood vessel (arteries and veins alike) where repeated injuries occur faster than the healing process can complete the necessary steps in the repairs.
If there's one publication I'd suggest you read- read the one linked to the right.
Â
Ok, so what's all that mean?
Well, my OPINION (not fact, just my take on it...) is this:
We know a plaque is essentially a spot where repeated injuries occur faster than the previous injuries can be completely healed. We know why it seems plaques appear in some locations but not others- mostly due to the nature of the flow of blood (smooth vs. turbulent).
To me, then it becomes necessary to figure out what the factors are that cause these injuries, and view it from that angle.
More, or less, anything that makes the blood thicker will cause it to 'swipe harder' along the walls. Anything that puts spikey kind of things in the blood will cause more pin-pricks. Anything that systemically affects the lining of the vessels where the lining becomes weaker will increase the injury rate.Â
According to the paper from above:
On the left- things that increase the thickness of the blood.
On the bottom- some medical terms that I don't know the meaning
Ultimately, this model shows us how the damage occurs such that a plaque is started. Armed with this mechanism, we can see how so many different and seemingly unrelated factors can contribute to the development and progression of Atherosclerosis.
And That's My Goal...
To understand the mechanism allows us to understand the causes
And that allows us to begin to prevention efforts that actually MATTER
Two more papers on this subject that I think are up in the 'gotta read these' section:
So, Does LDL move into the cells?
Yes. The process is called TransCytosis.
Watch Dave Feldman, this is fascinating...
(might pay extra attention to his summary at ~ 26:40)
Stopping here for now, July 2023...
There's a lot more to say, but for now I am curious what you think...
If you have corrections or suggestions, hit me up on email.
Be Good!
Curtis
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All Stop! I have another perspective- very important!
Bottom line, I pressed the 'lipid guys' pretty hard over on the blue bird.
While I learned that asking "what is the plausible mechanism whereby 'high' LDL-C, on its own, *causes plaques to form" is offensive to them and tends to draw out a lot of smug and condescending responses (none of which answer the question, by the way), I was provided with a number of new studies I had not seen before.
I can see why they INSIST that LDL-C (or apoB) *CAUSES* CVD
To sum it up-
The 'lesion-susceptible' arterial areas that are required for the plaque formation to start are areas that are associated with disturbed laminal flow of blood. More or less, areas where the blood flow is turbulent or aggressive as opposed to smooth.Â
The thing is- those are naturally occurring for every human being- our arteries have twists and turns and split off into smaller branches- all of which can produce these areas of what I call 'disturbed flow'.
More or less- we cannot control disturbed flow areas...
Which leaves LDL-C as the only controllable factor
So, I can see what they are saying, but...
I don't agree with some of the messaging surrounding this-
If a prior condition or triggering event is involved then high LDL-C or apoB are not the singular cause. That is just a simple fact.
Shouting loudly over everyone that it is-
1. misleads people towards thinking there's just one cause (wrong)
2. obscures viewing the other factors involved- preventing some from taking action where they could/should
3. invites complacency in providers and patients alike- 'just follow the guidelines' and shut up, no questions
4. Might discourage honest research (or in the case of some 'players' in this game- actively suppressing research)
Why can't there be a more accurate messaging about this subject? Why are seemingly intelligent and professional people declaring 'cause' (singular, on its own) when they know for a fact (as provided in the very papers they publish and refer to) that it is not?
Some facinating papers supporting...
"Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall"
https://www.ahajournals.org/doi/10.1161/ATVBAHA.115.305874
This is a fascinating paper that proves both my point that LDL-C (or apoB), alone, do not *cause* plaques to form, but also supports that maybe it might be the only factor that can be controlled- therefore it is the only 'causative' factor to focus on.
In this study in mice, they took a normally 'lesion-resistant' artery and put two sleeves around it.
One restricted flow, the other did not.
They then injected human LDL they could track and found the LDL deposited in the artery adjacent to where the flow was restricted, but not in the area of the other sleeve.
Non-restricted flow areas got no accumulation, but flow-restricted areas did...
So when human LDL-C was injected into the mice, LDL-C build up was *not* seen in the 'normal' (non-flow restricted) areas-
So, LDL-C (or apoB) appears to require a prior-condition or initiating event...
But without 'high' LDL-C, LDL-C build up was found immediately adjacent to the new flow-restricted area-
So, LDL-C concentration appears to be not only a causative factor- but the only factor under our control.
"The central role of arterial retention of cholesterolrich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity"
Probably a must read for those deeply curious like me, but fair warning- kind of hard to read with all of the language.
To me, this paper pushes me away from 'LDL-C' towards a focus instead on 'apoB', and...
It makes a great case for showing direct cause mechanisms in the face of pre-existing or initiating events.
For many people, this is enough...
For many, this is as far as they need to go. No need to go deeper, and, there's plenty of studies (they say, I haven't looked at them (yet)) that show lowering LDL-C with statins specifically improves CVD mortality and possibly even reduces existing plaques in some cases.
This appears to be the position of those folks who seem to get the most agitated with my questions, anyways...
My Current Conclusion/Understanding...
Response to Retention (Lipids cause it) Model
LDL-C and/or apoB presence in the blood do not *cause* plaques to form.
Higher concentrations lead to increased transcytosis of them into the vessels, but this does not appear to *cause* plaque issues system wide.
Disturbed flow areas in the vasculature exist, especially in the arteries, and are a factor beyond our control (lifestyle or medication).
Disturbed flow areas modify, in some way, that area of the vessel that leads to a build up of LDL-C/apoB.
This build up of excess LDL-C/apoB has a very clear sequence of biological steps that lead to plaque build up.
In the face of the factors for this particular pathway, the only one that can be controlled/influenced is LDL-C/apoB levels in the blood.
This model focuses on reducing LDL-C/apoB
Response to Injury (Lipids are one factor) Model
Injury to the lining of the artery leads to a normal process of healing.
Since having a scab slough of inside the vasculature might cause blockages, the body removes the by-products of the repair process from outside rather than inside the vein.
Microscopic investigation of plaques suggest the presence of the items associated with blood clotting and repair.
In areas where repeated injuries happen faster than the healing process can complete the repair process is the cause for plaques to form.
This model focuses on eliminating or reducing those items that might cause injury to the lining of the vessels.
Now, I have more questions...
One question surrounds the sub-components of LDL-C and what causes the 'improper' relative levels of those components. First, scope out these two videos:
O.K., so if you watched those, you'll know that cholesterol can be brought into the body through eating and it can be produced by the body.
But...
LDL is a package made in the liver- you don't "eat" LDL...
So the new question I have is...
Since the body is making LDL for specific purposes, is there a mechanism in play that affects LDL?
What causes LDL to rise?
Is it diet driven?
Is there a metabolic impact surrounding high blood glucose or insulin?
Is the 'problem' of LDL due to a fault in the process of making, circulation, delivery process, and/or re-uptake of LDL?
Is this not a 'high LDL' thing so much as it is a 'low HDL' thing?
Seems WAY more complicated than 'eat less saturated fat'
This goes a bit too far down the cholesterol path for an 'Atherosclerosis' focus, so I think I can stop here.
Look for a metabolism and also a cholesterol/lipid page coming soon...
In summary- my current understanding (July 2023):
There is merit in both the 'Response to Retention' and 'Response to Injury' models for how plaques start and grow.
ApoB, not LDL-C, appears to be the 'thing' to consider, track, and possibly minimize (within guidelines)
I'm not convinced eating saturated fat causes things to go awry with LDL since the liver makes LDL- so is there a problem in the liver that causes improperly high LDL to be made?
My personal plan-
- Low carb/zero carb diet to focus mostly on blood glucose control
- Habitually use CGM to assist keeping me focused
- I consume ZERO processed foods
- work on lowering BMI/Body Fat% (especially around abdomen)
- Intermittent Fasting with OMAD most days
- High intensity (sprints or bike) workouts alternating with bodyweight workouts
- Ritualized sleep- make sure to get good sleep, on a good schedule
- Metered sun exposure
- Water, Tea, Coffee only
- Continue zero alcohol, smoking, tobacco policy
Remember- This is NOT advice. In the spirit of sharing I insist that everyone realize that I-do-me and you-do-you...
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