Timeline of cholesterol research

Australian clinical pathologist Professor Ken Sikaris outlines the timeline cholesterol research has followed:

30 years ago

High cholesterol was thought to be a problem, while triglycerides were unimportant. It turns out that in some populations, low total cholesterol is actually a health risk.[65]

20 years ago

We understood that the two cholesterols that made up the total cholesterol (LDL-C and HDL-C) might have different effects. LDL-C was named ‘bad cholesterol’, as it was associated with increased poor health, and HDL-C ‘good cholesterol’ for the opposite reason.

• We now know that this is a simplistic picture: saturated fat increases both LDL-C and HDL-C, but has a differential effect on the size of the particles within LDL-C. Scientists also became aware that very-low-density LDL-C (VLDL) and oxidised LDL-C were likely to be markers of metabolic health.

• We also know that high levels of total cholesterol and LDL-C have been shown to be protective, not harmful, in some older populations.[66]

10 years ago

We developed a more nuanced understanding of LDL-C.

• The particle size of LDL-C can roughly be understood in terms of small dense particles (apolipoprotein B, or ApoB) that are potentially harmful to health, and large fluffy particles (apolipoprotein A, or ApoA) that are not thought to be part of the disease process.

• Trying to measure these in the blood requires an advanced biochemistry lab and is not standard (or even possible) in most pathology labs. While we know that it is better to measure ApoB and ApoA, we can’t measure them easily so are stuck with the LDL-C and HDL-C numbers for now.

Today

We now understand that the combination of fasting triglycerides and HDL-C (both usually measured in your standard blood test) is a good measure of ApoA/ApoB levels.[67]

• Low triglycerides are correlated with less ApoB and more ApoA, so a low triglyceride level predicts a better profile. Higher HDL-C levels are also correlated with less ApoB and more ApoA. These two correlations are independent of each other, so combining the TG and HDL-C numbers together gives an even better picture. A good level for the TG/ HDL-C ratio is less than 0.9 if measured in mmol/L or less than 2.0 if measured in mg/dL.

• The actual number of LDL particles can now be measured by LDL-P (LDL particle number). Low LDL-P is a much stronger predictor of low health risk than low LDL-C, probably because the higher particle number means more chance of oxidation (oxidised LDL is bad). Low-carb diets reduce LDL-P, while high-carb diets increase it.

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