Non-HDL Cholesterol

Lipidology, the specialty that deals with lipids, is an ever-evolving discipline, and not just because of the many new treatments on the horizon.
Patients have (for many) understood the notion of "good" and "bad" cholesterol without really knowing how to distinguish them on their test results.
We know that the concept of total cholesterol, still in use, does not allow us to make therapeutic decisions, as we cannot assess cardiovascular risk. Indeed, some patients have the misfortune to have an increase in "bad" cholesterol associated with a decrease in "good" cholesterol, resulting in a most "correct" total cholesterol.
As a result, a Lipid Anomaly Investigation (LIA) should be carried out from the outset, which will include: Total Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides (and sometimes a few unnecessary reports).

Ask your doctor! who, will tell you that Total Cholesterol is a reflection of all the cholesterol circulating in the blood, that "Good" Cholesterol is called "HDL" because it's carried by High Density proteins and "Bad" is LDL for "Low Density" (Yes you need to speak English). There are also triglycerides (TG), which are other lipids with a much less important role in damaging arteries: atherosclerotic plaques. In fact, it's LDL cholesterol that infiltrates, rather than deposits, in the artery walls, progressively clogging them, while HDL cholesterol returns to the liver to recycle cholesterol, thus playing the role of artery "cleaner".
It all sounds simple, too simple, but that LDL Cholesterol on the analysis sheet is really just the result of a calculation :

This is the Friedewald formula in daily use:
LDL cholesterol = Total cholesterol - HDL cholesterol - Triglycerides / 5.

This shows the importance of triglycerides in the calculation, and for values above 4 g/l, the calculation although mathematically feasible is no longer valid!!!
Serious laboratories indicate: "Not feasible" in these conditions, as the algorithm of certain devices "refuses" to perform the calculation.

How then?
Let's move on to the case where this is ignored... which is a double error:
- We do without LDL Cholesterol? It's complicated, since all the standards and recommendations for management are based on this figure.
- Using Total Cholesterol on an ad hoc basis: that's not serious.
- The real solution is to DOSE LDL cholesterol directly, as we do for HDL, but this is more complicated, only carried out in hospital laboratories (in conjunction with specialized lipid centers) and is obviously much more expensive than a simple calculation (which, by definition, costs nothing).
- Another parameter is used: The most accurate for determining cardiovascular risk is Apoprotein B (exactly B 100), which is closely linked to LDL Cholesterol but is not routinely measured, but rather here again in specialized Centers, although it can be seen in some so-called "complete" lipid check-ups.
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The recent alternative, just to simplify things by adding an extra element, is the concept of Non HDL Cholesterol. Physically, it doesn't exist, whereas LDL Cholesterol particles can be physically seen.
It still corresponds to an easy calculation:

Non HDL Cholesterol = Total Cholesterol - HDL Cholesterol.

His 3 advantages:
- It is always available since the calculation is based on these 2 measurements;
- It is totally independent of triglyceride levels;
- It globally reflects "everything that's not good about lipids": LDL Cholesterol, triglycerides and even the emerging element Lipoprotein (a).
In short, this is what we need to fight against. The European cardiovascular prevention guidelines have thus proposed for the assessment of risk by the SCORE calculation or equation, now SCORE 2 in the latest update, to replace Total Cholesterol (with its limits) with the Non-HDL Cholesterol still available.
This will change our habits, as doctors have been slow to get to grips with the use of LDL Cholesterol.
Yet non-HDL is no longer really a matter for experts, but is already used in practice (some laboratories supply it, it's so simple). And since it is included in the calculation of the new SCORE 2, it could (should) be the subject of specific recommendations, whereas for the moment it is only mentioned.


The trouble is, it's a concept, a practical one to be sure, but is it valid?
As usual, descriptive epidemiology is the first to respond, with two recent articles by the same team [1, 2] answering the question:Yes, Non-HDL Cholesterol is indeed associated with the risk of cardiovascular events, and this as early as childhood..
Intervention studies with new treatments should confirm this!
Et in our practice? Know how to interpret the results!
To simplify understanding of non-HDL Cholesterol, due to the way it is calculated, non-HDL Cholesterol is roughly 0.3 g/l above LDL Cholesterol, which is also calculated.
Clearly, a patient, whose LDL Cholesterol target is below 0.7 g/l (a fairly frequent case), should be roughly at 1 g/l non-HDL Cholesterol.

In summary:
- The LDL Cholesterol figure most often used is derived from a calculation.
- But this calculation is FALSE if triglycerides are above 4g/l.
- The LDL Cholesterol should be DOSED directly, but this is not applicable on a daily basis.
- Non-HDL cholesterol, on the other hand, is always available, the result of a simple calculation involving total cholesterol and HDL cholesterol. It corresponds to "everything that's not good".
- Knowing how to interpret the result - non-HDL cholesterol is à.3 g/L higher than LDL cholesterol.
- We're going to have to get on with it, as this concept could eventually "replace" LDL.

References:
1 - WU F. et al: Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events: Circulation: 2024;149(3):217-226.
2 - WU F. et al: Non-High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events: doi:10.1001/jama.2024/4819.