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Comment by Maxion | Hacker News Reader

LDL is almost always talked about as a singluar thing, even in scientific studies when LDL comes in several flavors.

Large bouyant LDL is not associated with CVD risk whereas small dense LDL is.

You can have high HDL, high LDL and low triglycerides. This is a pretty rare pattern, but one where you do not have increase risk of CVD.

In most people, having high LDL is linked to having high small dense LDL and low aounts of large boyant LDL. Hence why LDL is used as a simple risk measure - even though it's wrong.

Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.

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This doesn't really seem to pan out in reality. Often people with small dense LDL have it as a result of other risk markers. There's a good discussion here - https://www.youtube.com/watch?v=kplh30RmYo8 - the long and short of it is that when you perform mutual adjustment for number of particles, both large and small LDL particles are associated with a fairly similar risk. But if you have the same mass of cholesterol in two individuals (LDL-c) and one has SD LDL and the other has LB LDL, the latter has fewer LDL particles and therefore lower risk, so it can appear that LB LDL are less risky if you're only measuring cholesterol mass.

As for statins not working well in primary prevention, I'm not sure what you mean - the JUPITER trial showed significant risk reductions for primary prevention, for example.

The Jupiter trial clearly stated that those with low hs-crp didn’t benefit from LDL-C reduction, only those with high hs-crp had reduced CVD events due to LDL-C reduction.

The claim I was addressing was that we don’t have evidence of statin efficacy for primary prevention. My point was that JUPITER seems to be evidence this isn’t the case.

PCSK9 inhibitor trials have shown significant benefit for reduction in CVD events independent of whether or not the inhibitors lowered hsCRP. Ezetimibe makes an impact on events without reducing hsCRP when administered on it's own. (But it is generally administered with a statin, and it seems that the combination does result in lower hsCRP than a statin on it's own)

https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/ https://pubmed.ncbi.nlm.nih.gov/36779348/

> Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.

This just simply isn't true and we have massive quantities of data pointing towards protection against major vascular events - even in people that we previously would have considered as having "normal" cholesterol. The NLA and AHA has been revising their guidelines to start getting people on statins sooner and to get levels lower for a reason - it works.

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

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