Cholesterol Misconceptions
Distinguishing Between Cholesterol-carrying Particles and Cholesterol
“In all instances, the markers of particle number, apoB or LDL particle number- were stronger predictors of cardiovascular risk than LDL-C.” (II)
As I briefly covered in, “Check-It-Out #104,” I’ve been brushing up on some lipidology concepts as a part of an upcoming deep dive into saturated fat consumption and its impacts on cardiovascular disease risk.
In particular, I recently read through a 2022 review paper in which Glavinovic and Colleagues break down the evidence-based argument for the superiority of using apolipoprotein-B (apo-B) levels for assessing an individual’s risk of atherosclerotic cardiovascular disease (ASCVD; mostly heart attacks and strokes) as compared to low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and other cholesterol-based metrics . (I)
For those of you that read the Learning Lipids Series, you understand why I think this is important. On the other hand, for those of you who aren’t familiar with lipidology, I realize that this may all sound like a foreign language. But, I think you’ll also find it important considering that ASCVD is the leading cause of death globally.
For this reason, I decided to use this post to briefly cover what I see as the most common misconception people have about lipidology: the distinction between cholesterol-carrying particles and cholesterol.
SIDE NOTE 1: If you’re interested in diving deeper into this topic, I covered it in detail in the 5-part Learning Lipids Series.
SIDE NOTE 2: Dr. Peter Attia’s The Straight Dope On Cholesterol blog series and podcast series with lipidology expert, Dr. Thomas Dayspring, are terrific sources of information that I have heavily relied on to learn more about lipidology and ASCVD.
Medical Disclaimer: I am not a doctor, and none of the information below is medical advice in any way, shape, or form. You are responsible for conducting your own research, consulting your medical professionals, and making your own decisions.
Particles vs. Cholesterol
In my experience, most people are familiar with the terms LDL and HDL–standing for low-density lipoprotein and high-density lipoprotein, respectively–as these abbreviations come up on the routine lipid panels that primary care providers often order for their patients.
But, also in my experience, I think most people misconstrue what these terms actually mean. Specifically, I hear a lot of people refer to LDL and HDL as, “good,” and, “bad,” cholesterol, respectively. The first issue with this is that neither LDL nor HDL are cholesterol at all; rather, LDL and HDL are the protein complexes that carry cholesterol—also called cholesterol-carrying particles.
The idea that one is, “good,” cholesterol and the other is, “bad,” cholesterol is a whole other misconception with its own spiel for another post.
This idea is more easily understood if you consider what happens when you combine oil and water. Since the oil is non-polar and the water is polar (non-polar and polar being chemical properties determined by a molecule’s make-up and structure) they do not mix.
The same is true of lipids (non-polar), like cholesterol, and your blood (polar)—they don’t mix when you combine them. This is an issue because it means that cholesterol and other lipids will not flow in your bloodstream, which means they require a special mode of transportation to get them from one part of your body to another.
*Enter the lipoproteins*
Lipoproteins, like LDL and HDL, are analogous to vehicles that carry cholesterol and other lipids–namely triglycerides that are used as an energy source by cells across the body– through the bloodstream.
Ok, so, who cares?
Understanding this concept is important for understanding what the metrics on a standard lipid panel actually mean, particularly in terms of ASCVD risk.
For example, instead of the number of LDL or HDL particles in your blood, LDL-C and HDL-C reflect the amount of cholesterol carried by LDL particles and HDL particles in your blood, respectively.
These are the metrics people are correctly referring to when they say that they have high cholesterol—typically, they are referring to high LDL-C or high total cholesterol, a measure of the total amount of cholesterol carried by all particles in your blood.
And, importantly, they are also the metrics people are incorrectly referring to when they say they have high or low LDL or HDL.
Apo-B and LDL-P, on the other hand, are examples of particle-based metrics that do tell you how many particles of a given lipoprotein are in your blood—in these two cases specifically, they tell you how many LDL particles are in your blood.
But, does it matter whether it’s the particles or the actual cholesterol within the particles that comes back as elevated in your blood?
The short answer is that, according to the Apo-B Model of Atherosclerosis, it does matter because particle-based metrics more accurately predict ASCVD risk.
In particular, this makes a difference when a person’s cholesterol-based metrics and particle-based metrics are discordant: when one suggests a high risk of ASCVD and the other suggests a low risk of ASCVD. (I, II)
“If the mass of cholesterol per apoB particle were invariant, LDL‐C, non–HDL‐C, and apoB would be identical predictors of the risk of cardiovascular disease. If so, there would be no reason to measure atherogenic particle number rather than LDL‐C or non–HDL‐C. However, the cholesterol mass per apoB can vary substantially. The result is that at any level of apoB, there is significant variance in the mass of cholesterol per apoB particle. The result is that LDL‐C and non–HDL‐C are imperfect surrogates of apoB.” (I)
According to the Apo-B Model of Atherosclerosis, in these cases of discordance, the particle-based metrics reflect a person’s true risk of ASCVD. In other words, when it comes to ASCVD risk, it’s more important how many cholesterol-carrying particles are in your blood than it is how much cholesterol there is in your blood. (I, II)
“Multiple methods have been used to create the discordant groups, ranging from division at the median of the markers to separation based on residuals. These different definitions have resulted in discordant groups that range from about 20% to about 60% of the total population. In all instances, the markers of particle number, apoB or LDL particle number- were stronger predictors of cardiovascular risk than LDL-C.” (II)
Since I’ll probably keep rambling on about lipidology for pages if I don’t stop here, I’ll leave it at that. But, if you’re interested in reading more on this topic, I wrote plenty previously in the Learning Lipids Series.
For now, you’re equipped with what I find is the most commonly misconceived–and, in my opinion, one of the most important–concepts of lipidology: the distinction between cholesterol-carrying particles and cholesterol.
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