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:
| |
First of all, the misinformation on labeling lipid
metrics is one of the things that it’s a miracle hasn’t given me a
stroke yet. I do a lot of peer review. I’m one of the associate editors
of the Journal of Clinical Lipidology, and I will reject a
paper instantly that uses improper lipid metrics. Don’t tell me the LDL
is this, because LDL is a low density lipoprotein. It’s not a laboratory
metric. You want to tell me what the LDL-cholesterol is, the LDL particle
number is, the lipidomics of an LDL, is the LDL oxidized or not? Great.
We do have assays that will measure all of those. Don’t identify yourself
as an ignoramus. And look, I’ve told this to many of the top lipidologists
in the country, well actually,
“Stop telling people, what’s your LDL.” |
|
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-CNIH
LDL-C (Friedewald), herein LDL-CFriedewald
LDL-C (Martin-Hopkins), herein LDL-CM-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-CNIH
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-CNIH not being
reported if TG is over 800 mg/dL (yikes!).
LDL-CFriedewald 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-CM-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]
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