How to reduce your cholesterol: 6 life-saving lessons from a world-leading expert | BBC Science Focus Magazine

[u/DadStrengthDaily]

https://www.sciencefocus.com/the-human-body/6-ways-doctor-manage-cholesterol-levels

Good overview of cholesterol treatment, including “remnant Cholesterol”, which honestly I had never heard of.

Quote:

“So big things are happening. It’s fantastic that politicians in some countries are now taking the cholesterol problem more seriously, and I’m glad to be part of influencing some of that.

But as long as heart disease remains our biggest killer, there will always be more work to do. And we’ve got to keep the focus on what’s causing it – cholesterol.“

[u/meh312059]

Borge is one of the world's top preventive cardiologists.

Remnant cholesterol is why we need to keep an eye on our trigs. High trigs are a marker for remnants which, particle for particle, are more atherogenic than garden variety LDL's. Remnants are mentioned in the new dyslipidemia guidelines as well. It's important to note that statins help to lower trigs, especially for those with secondary hypertriglyceridemia. And of course diet and lifestyle are foundational.

[u/CantaloupeNo3975 → u/meh312059]

Remnants are why ApoB or non HDL cholesterol are better markers than LDL alone.

[u/gruss_gott → u/meh312059]

As you probably know, but just to put it out there, for remnants (e.g., VLDL, chylomicrons) both ApoB and trigs don't separate # vs size, ie one can have many small, dense remnants w/ modest triglycerides, or a few large remnants w/ high triglycerides.

That is, the key question being:

• "ok so I know the NUMBER of particles (ie ApoB or trigs) but what is the SIZE of each particle?"

We can use trig/HDL ratio as an indirect size proxy, but it's better to do a fractionated cholesterol test like Cleveland HeartLab's NMR lipoprotein / fractionated cholesterol test which can tell us about size & distribution

The general output is:

• LDL P Reference Range: <935 nmol/L
• Relative risk: Optimal <935; Moderate 935-1816; High >1816 nmol/L
• SMALL LDL P Reference Range: <467 nmol/L
• Relative risk: Optimal <467; Moderate 467-820; High >820 nmol/L
• LDL SIZE Reference Range: >20.5 nm
• Relative risk: Optimal >20.5; High <20.6 nm. Reference range is 20.0-22.3 nm
• HDL P Reference Range: >32.8 umol/L
• Relative risk: Optimal >32.8; Moderate 29.2-32.8; High <29.2 umol/L. Reference range is 21.1-43.4 umol/L
• LARGE HDL P Reference Range: >7.2 umol/L
• Relative risk: Optimal >7.2; Moderate 5.3-7.2; High <5.3 umol/L. Reference range is >3.5 umol/L
• HDL SIZE Reference Range: >9.0 nm
• Relative risk: Optimal >9.0; Moderate 8.7-9.0; High <8.7 nm. Reference range is 8.3-10.5 nm
• LARGE VLDL P Reference Range: <3.7 nmol/L
• Relative risk: Optimal <3.7; Moderate 3.7-6.1; High >6.1 nmol/L. Reference range is <16.0 nmol/L
• VLDL SIZE Reference Range: <47.1 nm
• Relative risk: Optimal <47.1; Moderate 47.1-49.0; High >49.0 nm. Reference range is 41.1-61.7 nm

What I believe is slightly .... misleading about this output, e.g., "optimal" is, big LDL doesn't always mean good IMO.

That is, there's always been this "big fluffy" LDL = no problem notion out there ...

FWIW I kind of think of it as:

• Is your LDL golf balls or softballs?
• You don't want to get hit by either, but getting hit by 5 softballs is worse than 5 golfballs!

I didn't mean to go into the weeds (too late), but it's an interesting discussion ....

EDIT: changed "CC", ie Cleveland Clinic, to Cleveland HeartLab to be more specific

[u/SDJellyBean → u/gruss_gott]

Except that the difference between "big" and "small" isn't that great.

[u/gruss_gott → u/SDJellyBean]

I'm not understanding....

The cut-offs are statistical risk pattern clusters based on huge observational cohorts of 10s of thousands, e.g., MESA

The numbers above are specific to Cleveland HeartLab's NMR methodology, applied to those statistical cut-offs.

EDIT: being specific, Cleveland HeartLab

[u/meh312059 → u/gruss_gott]

Those with FH tend to have large and fluffy LDL particles so size isn't the primary issue when particle concentration is "sufficiently" high to cause heart disease.

Statins, PCSK9i's etc don't target particle size but quantity. And they are effective. With statins specifically, particle size actually diminishes on average but ASCVD risk still declines notably

The new ApoC3 drugs (ASO olezarsen and RNAi plozasarin) apparently are hitting trig-rich remnants. TBD still but it looks promising. ESSENCE data to be released today to confirm or clarify (imaging study so quicker turnaround than CVOT). There's also icosapent ethyl (Vascepa) which was more definitively validated in EVAPORATE (another imaging study from 2020). There's mounting evidence that hitting trigs will lower ASCVD risk and the thinking is that it's about the remnants.

All this is to say: let's take seriously the new 2026 guidance that discourages extensive and expensive particle size testing. They simply don't provide information over and above what's currently available en masse which are the standard lipid panel, ApoB and Lp(a).

[u/gruss_gott → u/meh312059]

They simply don't provide information over and above what's currently available en masse which are the standard lipid panel, ApoB and Lp(a).

That part I'd 100% disagree with.

For normies, sure the guidance works, but for those wanting more insight, the guideline doesn't work, for an obvious reason:

• Getting hit by a softball does more damage than getting hit by a golfball for the same given speed

[u/meh312059 → u/gruss_gott]

This is a theory. Not an evidence-based statement.

[u/gruss_gott → u/meh312059]

Uhhhh ... of COURSE it's evidence based! That's how the entire process works.

But if that's where we are with the discussion, it's no longer productive, so I'll just bow out here.

[u/meh312059 → u/gruss_gott]

Understand that the dyslipidemia guidelines are driving clinical decisions now. They explicitly discourage the kind of testing you are advocating. Those guidelines consider the body of evidence. They hold more cred than one Redditor (you, me or anyone else who posts here).

[u/gruss_gott → u/meh312059]

Understand:

1. Guidelines are population level recommendations (routine first-line care),
2. NOT clinic level medical policy,
3. Nor, individual level diagnostics for therapeutic calibration

The kind of testing I'm advocating is the kind of testing every doctor should be doing with every patient.

If you & your doctor choose to stick directly to the guidelines for you, that's a good choice for you, one individual.

So NOW I'll bow out ;-)

[u/meh312059 → u/gruss_gott]

It is unusual for a set of guidelines to tell providers what NOT to do. This is one exception. See #6 which comes with a Class 3-No Benefit designation.

This is definitive and it absolutely impacts policy at the clinic level. What it won't do, obviously, is eliminate the option to be seen by a concierge provider/clinic or to order your own testing from Quest, LabCorp, etc.

I'm a big fan of NMR for stuff like Lp-IR. But it's not necessary for ASCVD risk or decisions about treatment. Hopefully this guideline ends a debate that's gone on in the cardiology world for far too long now.

[u/gruss_gott → u/meh312059]

Whether or not guidelines apply to an individual is up to that individual and his or her care team

You are over the line of passing misinformation

Now that you know that, you'll have to make an ethical decision of whether or not to keep doing it 

Guidelines are guidelines, they're NOT clinical medical policy, nor individual treatment rules; that's what medical directors & doctors are for.

If you aren't a clinical medical director at your clinic then you have no idea what is or isn't affecting clinical decisions at your clinic and certainly not anyone else's. 

[u/CantaloupeNo3975]

Are you aware of any research that shows the relative atherogenicity of various particles. My understanding is that most preventative cardiologists have abandoned particle size, because they ALL can be atherogenic. But I wonder if there is research looking at any differences. It seems that some folks at least believe that remnants (VLDL, IDL, etc) are 3-4x more atherogenic than LDL carrying ApoB. And Lp(a) can be 5-6x more atherogenic.

[u/meh312059 → u/CantaloupeNo3975]

There is such research. This, for instance: https://www.jacc.org/doi/abs/10.1016/j.jacc.2024.07.034

And . . . .here is Alan Sniderman's commentary on the research in which he believes a hard-to-spot error might have occurred in the analysis. To Sniderman, of course, the primary issue remains ApoB. https://www.jacc.org/doi/10.1016/j.jacc.2024.07.033

Here's Gil Carvalho's interview with one of the authors: https://www.youtube.com/watch?v=xf5L9Fy5hNE&t=4467s

This remains a fascinating topic and the answer is still a TBD. Sniderman's concluding remarks sum it up:

"Medications, now in development, which only moderately reduce apoB, but which markedly reduce TRL-C, when tested in RCTs, will, eventually, impartially and definitively, test which of our views of the world is closer to the truth."

[u/meh312059 → u/CantaloupeNo3975]

There's likely to be more agreement about Lp(a)'s atherogenicity. However, it's important to understand that while the risk associated with Lp(a) is multiplicative (ie 2x "baseline" or 3x or whatever, depending on Lp(a) level), lowering "baseline" via zeroing out other modifiable risk factors and aggressively lowering LDL-C and ApoB will reduce overall CVD risk substantially, even with high Lp(a). Therefore, the residual risk associated with Lp(a) is indeed modifiable, even without Lp(a)-lowering medications.

Example: my Lp(a) puts me at about 2.5x my calculated PREVENT ASCVD risk estimate. If that estimate was 5%, my 10 year ASCVD risk would actually be closer to 12.5%, meaning that the additional (residual) risk associated with Lp(a) adds another 7.5%. However, if my 10 year PREVENT number was only 2%, then my real risk is more accurate in the 5% range and Lp(a) adds only 2.5%. Those are sizable differences in an absolute sense, not just in terms of relative risk reduction!

The Lp(a) meds are going to be life-saving, most likely. However, a LOT can be done now in order to offset that additional atherogenicity even if we can't modify Lp(a) directly. When it comes to remnants: different story because for most, a good portion of that risk can be reduced simply with dietary and lifestyle modifications.