LDL: To C or not to C

Edition: 2021-08-28

Just what does the "C" in LDL-C stand for? I’m getting less certain every day. Some sources report that it stands for "Cholesterol". Other sources report that it stands for "Calculated". Even if we nail that down, we’re still a long way from the whole character string being an abbreviation of anything remotely useful.

LDL

These initials stand for Low Density Lipoproteins. When this abbreviation is used with no further qualification, it’s completely useless. When I see it, I assume it’s been spoken or written by someone seriously careless or under-informed.

Here’s lipidologist Thomas Dayspring being pretty blunt about it:

As LDL-Cholesterol

On the standard lipid panel, is the LDL estimated or measured, and in either case, how? If we know the “-C” stands for “cholesterol”, the number is still a complete mystery.

On the standard panel, of course, the TG and HDL numbers are quite useful. The TC not so much. VLDL-C, if present, may be a flat out insulting joke (TG÷5). The “LDL” number is why this page is here.

As LDL-Calculated

If we know the author/speaker means “calculated”, we’re likewise not much further along. As LDL-Calculated or calculated LDL-C, we now at least know it’s a guess, based on a standard lipid panel (usually CPT Code 80061), but which guess? The top forms of calculated LDL estimate are:
LDL-C (NIH), herein LDL-C_NIH
LDL-C (Friedewald), herein LDL-C_Friedewald
LDL-C (Martin-Hopkins), herein LDL-C_M-H
LDL-C (other: Iranian, Hatta or Puavilai)

We often don’t see them identified as such, and they need to be. What these calculations all have in common is that they are trying to torture 3 actual measurements (TC, TG, HDL) into confessing something that they don’t really know, namely: do your LDL particles include any that are atherogenic.

LDL-C_NIH is the new idol.
Any lipid panel you get in 2021 or later may declare “LDL Chol Calc (NIH)”. As of 2021-02-01, per Stanford Lab, NIH has finally trashed Friedewald, but since NIH also stands for the well-known institutional syndrome of "Not Invented Here", apparently NIH figured they could also improve on Martin-Hopkins. So they’ve come up with yet another way to torture the actually-measured lipid markers (HDL,TC,TG) in an effort to get them to confess something they don’t know.

I’ve replaced dashes with underscores here, to avoid confounding with minus signs. The new contortion (for mg/dL, presumably, and not ISO UoM) is:
LDL_CNIH = TC÷0.948 - HDL_C÷0.971 - (TG÷8.56 + [TG×NonHDL_C]÷2140 - TG²÷16100) - 9.44

Lest you assume that there is some new measurement here, probably not:
NonHDL_C = TC - HDL_C
per Dayspring

And the "C" in HDL_C apparently means "cholesterol" and not yet-another "calculated". If so, the final new impressive fiction is then:
LDL_CNIH=TC÷0.948-HDL_C÷0.971-(TG÷8.56+[TG×(TC-HDL_C)]÷2140-TG²÷16100)-9.44

And on the actually useful measure TG, the Stanford summary concludes with the destructive:
The NIH equation performs equally well in both fasting and non-fasting states.
Translation: equally useless, as the important TG number can be significantly distorted in fed state.

NIH is rapidly replacing Friedewald, and appears to have completely deprecated all the other pretenders to the throne of:
most impressive fake LDL number to scare patients with.
Note, however, that if LDL-C is completely missing from a lab report, it may be due to LDL-C_NIH not being reported if TG is over 800 mg/dL (yikes!).

LDL-C_Friedewald is now out to pasture,
but any "LDL-C" values you have from 2020 or earlier are apt to be based on its much cruder fiction:
  LDL = TC - HDL - (TG ÷ 5) (in mg/dL)
Dr. Davis has written about this folly many times. Here’s one: How To Get Off Statins

LDL-C_M-H is now fading.
Martin-Hopkins was gradually replacing Friedewald until NIH arrived. You may still encounter it in recent reports.

In the Friedewald approximation, VLDL is presumed to be TG÷5. M-H used the same approach, but replaced the 5 with a variable factor from a table.

Converting between NIH, Friedewald & M-H is possible.
just by re-running the calculations from the actual measurements. But doing so is a complete waste of time.

If low density lipoproteins matter, and they do, they need to be actually measured, which leads us to the next mess sometimes encountered with standard lipid panels.

As Measured “Direct” LDL[-C]

This (CPT Code 83721) is also known as Direct LDL-C, Direct LDL, DLDL or LDL-D. It actually measures LDL, but still lumps all the subfractions together.

When TG is above 400 mg/dL (also yikes), the lab doing the lipid panel may silently perform a DLDL and report that.

LDL-P: What We Really Want

Low Density Lipoproteins do matter, and deserve to be actually measured, not guessed at. Lipoprotein subfractions can be measured, and assays for this have been available for “only” about a quarter century now. Why they aren’t used more often, if not routinely, says a lot about the supposed specialty of cardiology.

There are three major assay methods (all still based on a simple blood draw):
  NMR (Nuclear Magnetic Resonance), CPT Code 83704
  VAP (Vertical Auto Profile), CPT Code 83701
  Electrophoresis: CPT Code 83700

NMR is the preferred test on this site. In addition to being the assay that Dr. Davis recommends, it’s the one most familiar to the readership. The key value is:
  NMR Small LDL-P (target: < 200 mmol/L)
and this is a number that cannot be teased out of a standard lipid panel (although when you get an NMR, you’ll probably get another lipid panel anyway).

VAP and electro can be useful, if you have a skilled practitioner who is familiar with them. VAP was off the market for a while, and is now back, but the Undoctored program hasn’t yet re-evaluated it for suitability.

The total LDL-P Particle Number is no longer a key focus. Dr. Davis: “…high or highish LDL particle number in the absence of small LDL particles is a gray zone: We do not know how atherogenic (plaque-causing) this situation is. My suspicion is that it is not plaque-causing or is minimally so, as we have had plenty of people with high LDL particle number, all large, with zero heart scan scores.”

Confounders and Closing Remark

Since it’s almost always the case that at least something has been measured, it’s further necessary to know if the test was done fasting, and not in the context of any weight loss in the preceding 30 days, both of which distort lipoproteins generally, and TG in particular. If these criteria aren’t met, even an actual LDL-P measurement is not useful.

Needless to say, if you’ve ever heard…

“I’m prescribing a statin for you
because your ‘LDL’ is too high”

…you might need to be looking for a real doctor.
___________
Bob Niland [disclosures] [topics] [abbreviations]