Cholesterol and Vascular Disease: Part 2: LDL-Cholesterol is Important, but LDL-Particle Number is Far More Revealing

September is National Cholesterol Education Month. In support of this important educational initiative we are republishing our six part series on cholesterol and the role it plays in cardiovascular disease.

Note: Seventy-one million American adults have high cholesterol, but it is estimated that only one-third of them have the condition under control.

We left off with part 1 of the Cholesterol and Vascular Disease blog concluding that the two key assumptions made by cholesterol scientists in the 1940s and ‘50s were wrong. These assumptions were: 1. All LDL particles are the same size and 2.  All similarly-sized LDL particles have the same cholesterol content. Had these assumptions been correct there would have been no need to evaluate any other LDL parameter beyond LDL cholesterol. Given the fact that they are wrong however, means that looking simply at LDL cholesterol allows for the persistence of significant and dangerous “hidden risk”.  And risk that is hidden is risk that will not be corrected. Therefore we must dig deeper into this issue and how it can translate into a higher risk for developing arterial plaque.

First, let’s deal with the size issue. We now know that many individuals have very small LDL particles, while others have large, normally-sized particles. The larger the LDL particles, the more cholesterol they can fit within them. Smaller particles on the other hand cannot carry nearly as much cholesterol as their larger brethren. (That is simple enough. A large bucket holds far more water than a tiny cup.) Therefore, if you have very tiny LDL particles, you need many more of them to generate an LDL cholesterol content (LDL-C) than someone with very large particles. (Back to the water analogy –  If you need to carry a quart of water and you have one quart-sized bottle, you can carry all the water in one bottle. If you have only cups available, you will need four of them to carry the same amount of water.) The result of this disparity in LDL size is that two people with the same LDL-C (130 mg/dL for example) will have very different LDL particle numbers when their LDL particles are very different sizes.

The second erroneous assumption was that similarly-sized LDL particles always carry the same amount of cholesterol within them.  This too has turned out to be false.  Under certain metabolic conditions – diabetes, obesity, overweight, high triglycerides, low HDL– LDL particles tend to be under-filled. Once again in these patients in order to generate a particular LDL-C level, more particles are required.  (Back to the water analogy – if you have only cups available to fill, but are permitted to fill them only half way, it will take twice as many cups to carry the same amount of water as your friend who is allowed to fill the cups to the very brim.) Therefore, two individuals with precisely the same LDL-C can have vastly different LDL-Ps. So the bottom line is that LDL-C is NOT a good surrogate for LDL-P after all. OK, you buy that, but you might now be asking yourself,” Does it really matter if I have a lot of LDL particles?” A common and excellent question with a simple answer – YES! This is because more particles translate into a higher risk for developing plaque.  And the reason this is so, is actually quite intuitive. The more LDL particles a person has bouncing around in the blood stream, the more likely the particles are to encounter and penetrate the walls of his/her arteries. (The shotgun vs. the pistol is another helpful analogy. Even if you are an expert marksman, you are much more likely to hit your target with a shotgun than a single-shot pistol.) This is important because the penetration of our arteries by LDL particles initiates the process of atherosclerotic plaque formation. Yes, it all begins with a single particle. Next week we will discuss how such simple LDL particles can initiate a process that still kills more Americans than any other disease.

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