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> What we are explaining is that cholesterol alone does not cause heart disease. It is cholesterol plus inflammation that causes heart disease.

interesting idea which I have heard before. However so far as I can tell we don't know if it is true. It seems to fit the evidence that the two are independantly causes of heart attack, when combined it is worse.

maybe someday science will figure this out but it is not easy and so will take a while. Until we do I avoid saying things with high confidence.



Cholesterol is more of a proxy "smoke" or "firefighter" measure than a measurement of the actual fire. It's very much a wet streets cause rain kind of thing.

Artificially eliminating the firefighters doesn't necessarily mean you've solved most of the problem.

Heart disease is a far more complicated problem than "cholesterol" or "cholesterol + inflammation", but humans and patients mentally gravitate to silver bullet thinking, which makes it really hard to work with. One interesting measure I've encountered is the lipid clearance rate, but it costs something like +$20k to measure and is not something a doctor can order from a lab; it's typically only performed in research settings.


This isn't necessarily true. High content of certain cholesterols in the blood does cause heart attacks. It doesn't just indicate it - it actually causes it.

And, we have shown the mechanism of action. Certain cholesterols will build up on artery walls, constraining the flow of blood. When there is too much build up and/or the vessel is too narrow, blood can be constrained too much, causing loss of blood flow and therefore oxygenation. The heart has MANY capillaries and requires a lot of oxygen.

This is really for real.


Comments like these just aren't based in reality. LDL levels are not a proxy or a wet streets cause rain. We even have a strong understanding of the mechanisms in which cholesterol causes things like heart attacks, strokes, peripheral arterial disease, etc. etc. etc. Something has to deposit plaque in your arteries.

Yes, from a mechanistic standpoint, inflammation is also an important causal factor. Lp(a) is also an important factor for people that are genetically predisposed to high levels - it also deposits plaque, and is one of the reasons ApoB is recommended. Most people don't have worrisome Lp(a) levels but enough do that we've been missing them, and we now also have good treatments for them - PCKS9 inhibitors reduce it by ~1/3rd, and we have Lp(a) specific medications in phase 3 trials that are even stronger.

But we know that statins work. This is some of the most established science in health. I keep seeing claims in these comments from people stating otherwise, but it just doesn't match reality.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

We have MR studies on genetics that further reinforce this idea to a huge degree

https://pubmed.ncbi.nlm.nih.gov/28444290/

We also know that lowering LDL in and of itself lowers inflammation within the arterial wall, though this isn't necessarily reflected in hsCRP. We know that foam cell activation and cytokine signaling increase inflammation at the site of the plaque, which results in further deposition, and these require ApoB particles be depositing plaque there to begin with. Some PCSK9 inhibitors show zero change in hsCRP results yet still show less localized inflammation - due to the significant reduction in LDL-C and Lp(a) particles.

https://www.frontiersin.org/journals/cardiovascular-medicine...

Lowering inflammation also works for reducing events independent of lowering ApoB particles - colchicine works even though it does nothing there - but if we're really trying to stretch the fire analogy, it's more like LDL and Lp(a) are the years of unmaintained brush and flammable debris in a forest, and inflammation is the strong winds. Both can lead to the spread of fire even without the other, fire can still spread even in the absence of both, but having either and especially having both will greatly increase the risk of the fire continuing to spread.


And this is why it's sometimes worthwhile to read the entire thread. Thanks for writing.


I believe the JUPITER trial showed this. If I remember correctly you needed high inflammation for high ldl to matter in cardiovascular events.


PCSK9 inhibitors don't universally lower hsCRP ( https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/ ) but do lower adverse cardiovascular events https://pubmed.ncbi.nlm.nih.gov/36779348/

MR studies looking at genetics show a decrease in cardiovascular events with lower LDL/Lp(a) levels independent of other factors such as hsCRP

https://pubmed.ncbi.nlm.nih.gov/23083789/ https://www.nejm.org/doi/full/10.1056/NEJMoa1604304 https://journals.plos.org/plosmedicine/article%3Fid%3D10.137...

Lp(a), another plaque depositing particle also has been shown in MR to be an independent risk factor for CVD events regardless of hsCRP

https://europepmc.org/article/med/20032323 https://pmc.ncbi.nlm.nih.gov/articles/PMC5483508/ https://www.nejm.org/doi/full/10.1056/NEJMoa1109034




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