Latest evidence suggests LDL particle number (LDL–p) is a much more accurate predictor of cardiovascular disease risk than either LDL or total cholesterol.
Cholesterol is not technically a fat; rather, it’s classified as a sterol, which is a combination of a steroid and alcohol. Cholesterol is fat-soluble, and blood is mostly water. Therefore you don’t actually have a cholesterol level in your blood – it can’t dissolve. Rather, it is transported around the body by special proteins called lipoproteins. The two most important in cardiovascular disease are low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
Now imagine your bloodstream is like a canal network, and the lipoproteins are like barges that carry the cholesterol and fats around your body as their cargo.
Scientists used to believe that the amount of cargo ion each barge (i.e. concentration of cholesterol in the LDL particle – the LDL your doctor tests) was the driving factor in the development of heart disease.
Studies now show it is actually the number of the barges on the canals, in our analogy this represents the LDL-p, as with more traffic there are more collisions into the sides of the canals (our arteries where the endothelium (lining) of the artery is only one cell deep).
The raised number of LDL particles and triglycerides increases their chance of oxidation and repetitive damage to the endothelial lining causes inflammation, deposits and in turn atherosclerotic plaques to form in our arteries.
Causes of raised LDL-p
- Insulin resistance and metabolic syndrome.
Now our (LDL) barges don’t just carry cholesterol; they also carry triglycerides, fat-soluble vitamins and antioxidants. And there is a limit to how much cargo they can carry. Eating refined carbohydrates is associated with higher triglyceride levels. More triglycerides leaves less room for cholesterol. So the liver needs to make more (LDL) barges to carry the remaining cholesterol.
In summary 2 people may have the same amount of cholesterol but the one with higher triglyceride levels will have a higher LDL-p.
- Poor thyroid function
Thyroid hormone has multiple effects on the regulation of lipid production, absorption, and metabolism. It increases cholesterol levels by stimulating HMG-CoA reductase an enzyme in the liver.
Low thyroid hormone decreases the number of LDL receptors on the surface of cells in the liver and in other tissues which leads to reduced clearance of LDL from the blood and thus higher LDL levels.
Multiple studies have shown associations between bacterial infections like Chlamydia pneumoniae and H. pylori.
One theory is that LDL has antimicrobial properties and is directly involved in inactivating microbial pathogens. This has been confirmed by studies showing that mice with defective LDL receptors—and thus very high levels of LDL—are protected against infection by gram-negative bacteria like H. pylori.
- Leaky gut
When the intestinal barrier fails, endotoxins such as lipopolysaccharide (LPS) produced by certain species of gut bacteria can enter the bloodstream and provoke an immune response. Part of that immune response involves LDL particles, which as I mentioned above, have an anti-microbial effect. A protein called LPS-binding protein, which circulates with LDL particles, has been shown to reduce the toxic properties of LPS by directly binding to it and removing it from the circulation. (9) Studies have also shown significant increases in LPS-binding protein (and thus LDL particles) in cases of endotoxemia—a condition caused by large amounts of circulating endotoxins. (10)
Familial hypercholesterolemia, or FH, involves a mutation of a gene that codes for the LDL receptor or the gene that codes for apolipoprotein B (ApoB). The LDL receptor sits on the outside of cells; the LDL particle has to attach to the LDL receptor in order to deliver the nutrients it’s carrying and be removed from the circulation. ApoB is the part of the LDL particle that binds to the receptor. If we use a door lock as an analogy, apolipoprotein B would be the key, and the LDL receptor is the lock. They both need to be working properly for LDL to deliver its cargo and to be removed from the bloodstream.
Heterozygous carriers only have a single copy of the mutated gene, and the other copy is functioning normally. This is much more common. The prevalence is between 1 in 300 to 1 in 500 people, depending on which study you look at. These heterozygous carriers of FH have total cholesterol levels that often range between 350 and 550 mg/dL, along with very high LDL particle number. They have about three times higher risk of death from heart disease than people without FH if it goes untreated.
It’s important to note that people with FH have primarily large, buoyant LDL particles, and yet are still at much higher risk for cardiovascular disease. While it’s true that small, dense, oxidized LDL particles are more likely to cause atherosclerosis, large, buoyant particles can also be harmful when their concentration is high enough. This is one reason why LDL particle number is a superior marker to LDL particle size.
Interpreting your results
- LDL-p < 1000 – Optimal
- LDL-p > 1300 – Borderline
- LDL-p > 1600 – High Risk
- LDL-p > 1300 – Very high Risk