Learning Lipids Part I
Cholesterol 101
As the leading cause of death globally, atherosclerotic cardiovascular disease (ASCVD) is a hot topic of conversation from the mainstream media to doctor’s offices and the realms of health, fitness, and longevity . However, I’d bet most of the talk you’ve heard around heart attacks and strokes has less to do with the characteristics of the actual conditions and more to do with their most infamous underpinning: cholesterol. In this regard, I find an inadequate grasp on lipidology 101, like the distinctions between cholesterol and cholesterol-carrying particles (LDL and HDL) is one of the greatest sources of confusion and erroneous view points about ASCVD. For this reason, I’ve put together a deep dive on lipidology — similar to those I created regarding hangovers and caffeine — to explain basic lipid metrics, risk factors for ASCVD, lipid-lowering medications, lifestyle implications, and more. To begin, here is Cholesterol 101.
What is cholesterol?
Cholesterol is a type of lipid, a compound that is nonpolar and does not dissolve in water as a consequence. Lipids and your blood are analogous to oil and water, in that when you combine oil (nonpolar) and water (polar) in a container, they separate; similarly, if you put a lipid, like cholesterol, directly into your blood — a polar substance — the lipid would separate from the blood, rather than mix with it. Considering that many nonpolar compounds, such as triglycerides, cholesterol, and steroid-based hormones (estrogen, testosterone, etc.) are essential to human physiology, the concept that they cannot dissolve in blood presents a pivotal issue for which evolution found two solutions:
1. Utilize protein complexes with polar exteriors to carry those compounds.
2. Chemically modify the compounds to make them more polar and soluble in blood.
The latter solution explains some of the many compounds with the prefix, “free,” such as free testosterone, and is of less concern for this conversation. The former solution, on the other hand, sits at the core of Cholesterol 101. If you’re reading this, then you have likely visited a hospital lab, Quest Diagnostics, or something of the like to give blood because your doctor wanted to check your cholesterol. But what does, “check your cholesterol,” actually mean? For most, this phrase refers to the typical lipid panel containing cholesterol-related metrics, like LDL-C, HDL-C, Triglycerides, Total Cholesterol, and Non-HDL-C. In order to understand any of that though, we must first understand the previously mentioned solution to our solubility issue: the lipoprotein.
You can more easily understand the relationships between lipoproteins, lipids, and your blood through the analogy of a highway, where the route, vehicles, and contents within the vehicles are analogous to a blood vessel, lipoproteins, and lipids respectively. Since cars, trucks, and motorcycles traverse highways at rapid speeds, the environment on a highway is generally incompatible with pedestrians, similar to how the environment in the bloodstream is incompatible with raw lipids. For this reason, pedestrians utilize vehicles to travel down the highway, and lipids utilize lipoproteins with polar exteriors to travel through your blood. Now, similar to how vehicles on a highway carry a variety of different contents — people, food, water, furniture, etc. — lipoproteins carry a variety of different lipids, such as cholesterol, triglycerides, and phospholipids. With this in mind, you can think of cholesterol as the actual people traveling in the vehicles on the highway, triglycerides as the food and supplies traveling in the vehicles, and phospholipids as the structural pieces of the vehicles — such as the wheels, seats, etc. When a lab sends you lipid panel results, they are essentially sending you metrics that describe the concentrations of lipid-related contents in your blood — the amount and types of vehicles, people, and supplies on the highway. Now that you understand the big picture of Cholesterol 101, you can start to plug in the main players:
Metrics Found On a Typical Lipid Panel
High-density Lipoprotein Cholesterol (HDL-C): A measurement of the amount of cholesterol carried by HDL particles in a sample of blood. HDL particles represent one of the 3 major lipoprotein lineages. You can think of the different lineages as analogous to the different types of vehicles on a highway.
Triglycerides (TG): A measurement of the total amount of triglycerides in a sample of blood. Since the majority of triglycerides in your blood are carried by Very Low-density Lipoproteins (VLDLs), this metric is commonly used as a proxy for the amount of VLDL particles in a sample of blood.
Total Cholesterol (TC): A measurement of the total amount of cholesterol in a sample of blood.
Low-density Lipoprotein Cholesterol (LDL-C): A metric of the amount of cholesterol carried by LDL and IDL particles — though the vast majority resides in the LDL particles — in a sample of blood. This metric can be measured directly, or calculated by inputting HDL-C, TC, and TG into Friedewald’s Equation.
Friedewald’s Equation: LDL-C = TC – (TG/5) – HDL-C
Non-HDL-C: A calculation of the amount of cholesterol carried by particles other than HDL particles in a sample of blood.
Non-HDL-C Equation: Non-HDL-C = TC – HDL-C.
Particle-based Metrics Not Found On a Typical Lipid Panel
Apolipoprotein-B (Apo-B): A metric of the total amount of particles from the LDL lineage in a sample of blood. This metric leverages the fact that Apo-B 100 proteins are only present on lipoproteins from the LDL lineage — VLDLs, Intermediate-density Lipoproteins (IDLs), Lp(a)s, and LDLs. Since most of the Apo-B-carrying particles in a sample of blood are LDLs, this metric is a proxy for the number of LDL particles in that sample of blood.
LDL-Particle (LDL-P): A metric similar to Apo-B, that measures the total amount of LDL particles in a sample of blood — excluding the VLDL, IDL, and Lp(a) particles that an Apo-B measurement captures. Instead of using Apo-B 100 proteins for measurement, this metric uses nuclear magnetic resonance spectroscopy (NMR) for its measurement.
If you enjoyed this lipidology lesson and are interested in learning more, check out the resources below and stay tuned for Part II of this Learning Lipids series.