Image by David Cortez from Pixabay
Most of us think of LDL as “bad” cholesterol, while HDL is the “good” cholesterol. This is an oversimplification, though.
LDL stands for Low Density Lipoprotein, while HDL stands for High Density Lipoprotein. These are carrier proteins for cholesterol and triglycerides. A standard lipid panel will not measure the number of these particles in your bloodstream; instead, it measures the concentration of cholesterol within these particles. But this isn’t the most valuable test in terms of cardiovascular risk.
LDL Particle Numbers
While there are several markers you might test to determine the cardiovascular risk of your LDL, the most important is the total number of particles, not the concentration of cholesterol within those particles. Even if your cholesterol concentration, or LDL-C, is fine, you may still have an elevated number of LDL particles, or LDL-P. Conversely, if your LDL-C is high, you might still have low LDL-P, which would indicate low cardiovascular risk.
Apolipoprotein-B is a surrogate marker for LDL particle numbers, as each LDL particle contains this protein on its surface.
LDL-P may be elevated for those with metabolic syndrome and insulin resistance, as a feature of these conditions is elevated glucose. Glucose gets stored in triglycerides, and then packaged into LDL particles. This means there may not be enough space left over for cholesterol, so the liver compensates by increasing LDL particle production. Treatment in this case involves regulating glucose levels and insulin sensitivity.
Along those lines, metabolic syndrome is often associated with metabolic endotoxemia, always secondary to leaky gut syndrome. This process involves overgrowth of pathogenic gut flora which produce a toxin called LPS (lipopolysaccharides). LPS can get released into the bloodstream from a sufficiently inflamed gut. One of the mechanisms by which the body combats this is via a protein called the LPS-binding protein, which circulate along with the apoB on the LDL-P. Therefore, in the presence of metabolic endotoxemia, the body will increase LDL-P production. The treatment in this case, of course, is to heal the gut so that the leakage ceases.
Another possible cause of higher LDL-P is hypothyroidism. This slows down metabolism generally, particularly decreasing LDL clearance. Regulating thyroid levels should correct this problem.
Chronic bacterial or viral infections may also be to blame, though the mechanism of action for how this might affect cholesterol is unclear. I suspect it may be similar to that of hypothyroidism, broadly speaking: when the body is distracted, many of its usual functions take a backseat.
Less commonly, the problem is familial, and thus, genetic. In these cases, treating the symptom is appropriate.
LDL Particle Size
Another marker on more in-depth lipid profiles is the size of the particles. Smaller LDL are more likely to induce inflammation in the endothelial lining of the blood vessels, which triggers the series of events leading to plaque formation.
Of course the risk increases when both high LDL-P and small LDL coexist, yet small LDL is less problematic when LDL-P is within normal limits.
LDL particle size might be smaller in those who consume higher carbohydrate diets, particularly those high in sugar and white carbs–and these individuals would also be more likely to suffer from metabolic syndrome and thus, elevated LDL-P as well.
LDL particle size also tends to be smaller for those deficient in omega-3 fatty acids.
Just like smaller LDL are more likely to trigger endothelial inflammation, so too are damaged LDLs, including those that are oxidized and those that are glycated, or have a sugar attached to them (the same process that happens to hemoglobin to produced hemoglobin A1c).
Oxidation means that the LDL is missing an electron, turning it into a free radical scavenger. This means it will seek to steal an electron to complete its pair from whatever happens to be nearest. In this case, what’s nearest is the endothelial lining. The result is inflammation, leading to an increase in inflammatory markers, and eventually plaque formation.
The world is full of oxidative stressors. One way to mitigate them is to consume a diet high in food-based antioxidants, such as the Mediterranean Diet and green tea. Decreasing other systemic sources of inflammation such as chronic infections certainly plays a big role here as well.
While the traditional lipid panels are of some value, the deeper cholesterol testing including LDL-P, LDL size, and oxidized LDL can give a much better idea of overall cardiovascular risk.