Interesting study of something that "causes" atherosclerosis (hint: it's not LDL)

(Bob M) #1

https://www.jci.org/articles/view/158788

The first part of the abstract:

image

A lot of the data was developed using mice, though. Never know how those transfer over to humans.

(Bacon is a many-splendoured thing) #2

It’s interesting, how all these things correlate. There is a strong correlation between diabetes and obesity. There is a strong correlation between diabetes and cardiovascular disease and between obesity and cardiovascular disease, and there is a strong correlation between mental illness and obesity, and between diabetes and mental illness. In fact, it seems there are correlations between all of the chronic diseases from which people suffer, today, even though there are always people with A who don’t have B, and people with B who don’t have A. So perhaps there is a C that underlies all those A’s and B’s and causes them all?.

But I’m just a layman, and surely it can’t be as simple as it looks to me. Surely it’s the case—as the professionals tell us—that all of these diseases are multifarious and complex, and for some unknown reason, they all just—completely coincidentally, of course—happened to start bothering us around the same time. Surely the cause of all this couldn’t come down to a society-wide shift in diet. Could it? Surely the fact that all the chronic conditions seem to be related in some way to insulin-resistance and hyperinsulinaemia is just a complete and utter coincidence, right? Right?

(Bob M) #3

I think these people sometimes get blind to other possibilities. Once fat became the villain, LDL the villain, salt the villain,…they stop looking. They simply believe.

Now, I have no idea whether suPAR is actually causal, though the study is impressive. They use epi data, but then back it up with genetics and Mendelian randomization, and go even further by doing mouse studies.

But maybe this is like Lp(a): people are convinced that Lp(a) causes atherosclerosis, yet I have extremely high Lp(a) and a CAC score of zero. It is possible that Lp(a) could be a type of “accelerant”, so if you have the underlying mechanisms (such as a terrible diet) that actually cause endothelial dysfunction (part or all of Malcolm Kendrick’s theory of heart disease), then having a high Lp(a) could accelerate that. But it doesn’t cause it.

Even in this suPAR case, if you’re genetically unlucky to have higher suPAR, could it be that something like keto would help or even prevent atherosclerosis?

We’ll likely never know, because someone will invent a drug for this and try to make billions.

(Bacon is a many-splendoured thing) #4

You are right about that one.

This certainly seems to be the case.

Ravnskov and Diamond have posited hypercoagulability of the blood as the cause of cardiovascular disease. I’m not entirely convinced, but if it is true, then a diet that increases the glycation of haemoglobin (making blood clot more readily) would certainly exacerbate or stimulate that cause.

(Joey) #5

Just curious: Does your bloodwork indicate relatively low levels of systemic inflammation? If so, I’d imagine you’re in great shape with respect to CVD risk.

Based on my readings regarding CAC data, I’ve come to believe that Agatston scores are a useful but rather half-baked indication of what’s actually going on…

A zero CAC score = no calcification has been detected. Full stop.

However, calcification is the body’s response to arterial eruptions. It serves as a protective “scabbing” - where density and volume are highly relevant in terms of arterial health.

OTOH, non-calcified soft plaque (potentially dangerous to heart, brain, lung function if/when it becomes dislodged) does not appear on a CAC scan. The scan only detects calcification - i.e., scabbing.

So a scan lacking any calcification would indicate low CVD risk if and only if there is no (non-echolucent = undetected) soft plaque erupting in response from inflammation (that remains “unscabbed”).

To be clear, ceteris paribus, one would generally prefer to NOT have arterial scabbing rather than to have it. That is, unless there are soft plaque wounds (analogous to the clotting @PaulL refers to above which are undetected in a CAC scan) that would benefit from such scabbing. In which case, all else is not equal.

Agatston CAC scores are not density-oriented, so a more nuanced understanding of this topic is warranted. Which leads me to share something I recently prepared…

Attached is a summary of certain research I’d come across that I offered our family internist, who is very open-minded and interested in the latest science. It might be of interest here as the first topic included in this recap pertains to Agatston score interpretation:

ResearchRecap.pdf (57.6 KB)

[For our Doc’s convenience, I included hard copies of each paper cited. In your case, a simple google scholar search will bring them to your desktop.]

(Bacon is a many-splendoured thing) #6

My impression, from what you posted and from other sources, is that calcification is the late stage of artery repair. It is significant as an indicator of the existence of damage, but not a bad thing per se. My suspicion is that, while we eventually want the calcium to return to the bones where we really want it, it is doing good work in calcified plaque. Trying to move it out of the plaque may not be the best strategy, any more than picking at a scab on your knee is. We want healing, even if that means letting the scab continue to annoy us.

Ravnskov and Diamond suggest that arterial damage occurs frequently, but we have evolved to deal with it. We only notice arterial plaque and calcification when the rate of damage outstrips the rate of repair, such as when we eat, say, a diet that elevates insulin, which raises blood pressure, stiffens arteries, and interferes in other ways, when it is too high.

I’m not entirely sure about their hypothesis; I suspect that they are leaving out the extent of the damage from their thinking. I notice that a small cut heals rapidly and I barely notice it, but a large wound takes much longer to heal and the process of scabbing, etc., is much more involved. So I wonder if it’s not just that the rate of damage is higher, but that the damage is more severe.

“More research is needed,” as my favourite physicist likes to say.

(Joey) #7

Like you, I’m not convinced of the entirety of this view.

I don’t doubt arterial damage occurs frequently (viz., the incidence of atherosclerosis in an aging population). But evolutionary pressure in response would hinge on whether such damage often occurred before we were past the age of procreation. Typically, it occurs well after that point in life.

As such, I see no Darwinian selection pressure here. On the contrary - thinning the herd of older folks is often good for the tribe :wink:

Moreover, we evolved eating foods that were far less likely to cause calcification of the arteries. So, there’s that missing link in our shared ancestry, too. Why evolve to survive a threat we didn’t face?

And so my (admittedly biased) takeaway is this:

1 - Soft plaque (loose clot?) is caused by arterial inflammation. It can be deadly.

2 - Calcification is evidence of soft plaque being stabilized. It’s protective.

3 - I’d rather have neither.

4 - Therefore avoid things that cause arterial inflammation.

:vulcan_salute:

(Bacon is a many-splendoured thing) #8

Amen to that!

The body is a dynamic system, so the idea of constant minor damage and repair doesn’t faze me. But you’re right, it needn’t be the case, either. In any case, it does appear that the calcium is not part of the problem, but part of the solution. And we do know that people on keto have seen their arterial calcium slowly diminish over time.

(Marianne) #9

So interesting to me. I still am confounded that no one in my family or any of my friends can go toe to toe with me on either my HDL or triglycerides to HDL ration (or weight loss sustained over four years), yet I am the “unhealthy” one.

(Michael) #10

Thanks for the research, there were a couple I had not yet found. I am starting my deep dive into CVD myself, I expect it to take a few months before I will surface with a clear concept.

Currently I do feel that ROS cause consistent damage and that the rate of repair is relevant to whether there is sufficient accumulation of damage to cause soft plaque My doctor stated that a single CAC is worthless while a single CT-Angiogram tells you everything you want to know, so while I have already been waiting 6 months for a date, he ordered as much. In the meantime I may try and get my brand new GP to order a CAC scan now, and again in a year to compare.

If taking mk4 helps send the calcium within hard plaque back to bones, reducing the plaque density, would that lead to a higher risk? How do people safely clear plaque if not with this process? While preventing is best, reversing damage may be needed for most of us on these boards :pleading_face:. Yes, more research needed.

(Joey) #11

@Naghite Yeah, lots of (competing) theories to unpack.

The bones/teeth need to uptake calcium and K2 (MK4 and MK7) with D3 are associated with higher uptake. The less circulating around the blood the less likely it is to get deposited where it “doesn’t belong” … whether that implies it deprives arteries of needed-calcium for “scabbing” of soft lesions would seem to me to be a stretch - but who knows? :man_shrugging:

As for CAC scores, depending where you live it’s not necessarily a big deal … in much of the US you can get them without a doctor’s order for less than $100. My wife and I get annual CAC scans for $69 at a nearby hospital that advertises the service in hopes more folks get them done - usually around Valentine’s Day. It’s very romantic.

(Bacon is a many-splendoured thing) #12

I saw a comment from a woman who’d lost 100 pounds or so on keto (whatever the amount was, it was a lot), and suddenly her co-workers and friends were concerned about her health. She said she asked them where they had been when she was regularly eating doughnuts by the dozen.

I find it interesting that they tell us to lose weight, but then, when we actually do as we were told, it becomes a problem, lol! I’ve been collecting pictures of people taken before the dietary guidelines were introduced, and it’s amazing how many people look emaciated to our eyes today. Also, as I’ve mentioned in other threads, when I watched Houseboat on television in the early 1970’s, I was struck by how well-padded Sophia Loren looked, though I thought her very shapely. I recently did a search on photos from that movie, and now I am struck by how thin she looks, although just as shapely.

(Marianne) #13

I guess that’s okay, but heaven forbid you don’t eat vegetables! It makes no sense. I don’t give two crumbs anymore what people think.

(Blake) #14

I think most of us on here do know it’s just that simple…and stop calling me Shirley! :laughing:

(Bacon is a many-splendoured thing) #15

:rofl::rofl::rofl::rofl:

(BuckRimfire) #16

Wait, what? I haven’t heard of this (not that I’m encyclopedic in my knowledge of clotting). Do you have a reference to glycated hemoglobin promoting clotting, or is that just an association?

(Bacon is a many-splendoured thing) #17

Sorry—in the stuff I’ve read, it was taken as basic knowledge that didn’t need a citation. The notion seems to be that glycated haemoglobin is “stickier” than unglycated. I’ll try and find a biology text book that talks about it.

Of course, the body appears to be designed to cope with a certain amount of glycation, since red blood corpuscles lack mitochondria and must rely on serum glucose to stay alive. So I imagine that a normal level of glycation must factor somehow into the clotting cascade, and my guess would be that it’s only glycation above the normal level that is a risk.

(BuckRimfire) #18

My confusion is that hemoglobin is really only inside the RBC, while clotting is an extra-cellular phenomenon, so the HbA1c state shouldn’t affect clotting.

Tiny amounts of hemoglobin could probably be found in the plasma from rupture/lysis of RBCs, but that should be minimal, I thought. Your kidneys are pretty intolerant of hemoglobin in plasma; not sure if it’s the protein or iron load that hurts them.

Since nonspecific glycation by excess sugar is a body-wide problem, my uneducated guess is that glycation of hemoglobin associates with clotting problems caused by random glycation of other proteins. Two different forks in the same road.

(Joey) #19

A good read …