A Basic Guide to Cholesterol: Part I

Cholesterol is a substance that plays many essential roles in the body. It is involved in things like the structure of our cells, brain and nerve function, and hormone production. It is so important that every cell in our body can make all the cholesterol it needs without relying on high amounts to be delivered from the blood. Babies born without the ability to make their own cholesterol have severe birth defects and can die as a result. We can also consume cholesterol in certain foods derived from animals. It is frequently described as a fatty or “waxy” substance. While different from body fat, cholesterol and body fat are in the same family of substances collectively known as “lipids”.

One important characteristic of lipids, including cholesterol, is that they do not dissolve in water. This is due to their chemical structure. Think of when you try to mix oil and water – they really don’t like one another and will separate on their own. Because humans are mostly made of water, cholesterol won’t dissolve in the blood and needs help getting around. We have special carriers called “lipoproteins” to pick up things like cholesterol and other lipid substances that don’t like water to help them move through the bloodstream.

In this article series we will cover the basics of cholesterol and why we should care about it, what to do when it is high, and address a variety of related myths and misconceptions.

Why do we care about cholesterol?

We have known for a very long time that cholesterol in the blood is related to the risk of heart attacks and strokes. But the relationship between cholesterol and heart disease is complicated. For example, there are people who suffer heart attacks who do not have extremely high cholesterol levels. There are other people who have low cholesterol levels who die prematurely. This has created a lot of confusion and arguments about how important cholesterol really is and how concerned with it we should be. The short answer is that it is important and healthcare professionals are rightly focused on it, despite what many claim. We will explain these apparent contradictions and clarify areas of confusion throughout this article series.

Lipoproteins come in a variety of sizes, but many of them are extremely tiny – smaller than 70 nanometers in size, or 0.00000007 meters. Particles this small can penetrate the walls of our blood vessels. When this happens, they deposit their cholesterol and this causes inflammation in the vessel wall. These collections of cholesterol and inflammation are called “plaques”. Plaques can grow over time and limit blood flow through our vessels. They can also break loose and cause sudden blood clots that stop blood flow to important organs, resulting in problems like heart attacks and strokes.

When blood cholesterol levels are high for a long time, the tiny lipoproteins have more opportunity to get into our blood vessel walls and cause problems. Heart disease risk is related to how high these levels are, but more importantly how long they are elevated over the course of your whole life. ^{[Robinson 2018]} This is why many heart attacks and strokes occur in older people who have had decades of exposure to milder elevations in blood cholesterol, but it is also possible for people with extremely high levels to have these problems earlier in life too. In fact, about 40% of these events happen in people younger than 65 years.

However, risk is not “all-or-nothing”. In the same way that not everyone who smokes throughout their life will develop lung cancer, some people with higher cholesterol levels may not experience a heart attack. Regardless, the risk is still present, depending on the total levels over the entire lifespan. The earlier in life we get blood cholesterol levels under control, the lower the risk of heart disease in older age. On the other hand, waiting until old age to start treating patients for high cholesterol has much smaller benefit, since a lot of the damage has already been done.

Blood cholesterol levels are not the only contributor to heart disease and strokes. Other things like smoking, high blood pressure, diabetes, and inflammation are very important too and will be covered in separate articles. But even when people do not have any inflammation, have normal blood pressure and blood sugar, and do not smoke, higher blood cholesterol still increases the risk of heart disease compared with lower cholesterol. ^{[Yusuf 2004] [Friera 2017]} Fortunately we have learned about lots of things that influence blood cholesterol levels and heart disease risk. This has led to many effective treatments and a massive decrease in heart disease deaths since the mid-20^th Century.

How is high cholesterol diagnosed?

Most people who see a primary care doctor will have a cholesterol test done at some point. Recall that there are many things that do not dissolve in water that need to be carried around the blood on lipoproteins. A cholesterol test measures how much of these are in the blood.

1. Total cholesterol (TC): this tells you total amount of cholesterol being carried on all lipoproteins.
2. High-Density Lipoprotein-Cholesterol (HDL-C): this tells you the amount of cholesterol being carried on a specific lipoprotein called “HDL”. This is often called “good” because having higher levels of HDL-C is associated with less heart disease. Unfortunately this is just a correlation – not a causal relationship, which is why research has shown that doing things to increase this level does not help.
3. Triglycerides (TG): these are a form of fat that is carried on lipoproteins. Lipoproteins deliver triglycerides to our organs and tissues, where they are burned for energy. While an important contributor to heart disease risk on their own, we will spend less time on them in this article. Extremely high levels (greater than 500 mg/dL) require aggressive medical treatment to prevent other complications. Otherwise, follow the remaining discussion.
4. Low-Density Lipoprotein-Cholesterol (LDL-C): this tells you the amount of cholesterol being carried on a specific lipoprotein called “LDL”. This is often called “bad” because LDL is the main – although not the only – lipoprotein that gets into blood vessel walls, depositing cholesterol and setting off the inflammation that causes plaque to grow. There is some variation in the size of LDL particles, but all of them – large or small – typically range from 20-30 nanometers in size, much smaller than the 70-nanometer threshold to get into the walls of our blood vessels and cause trouble.

We can see that there are multiple different components of a standard cholesterol test. If someone is told they have “high cholesterol”, which numbers are we talking about? Let’s try to simplify.

By taking the total cholesterol (TC) and subtracting the high-density lipoprotein cholesterol (HDL-C), we obtain a number known as non-HDL cholesterol (non-HDL-C). Subtracting the “good” stuff from the total amount leaves us with an estimate of all the “bad” stuff; that is, all cholesterol being carried on lipoproteins that can be harmful. For example, consider the following blood test results:

• Total Cholesterol: 200 mg/dL
• High-Density Lipoprotein Cholesterol (HDL-C): 50 mg/dL
• Triglycerides: 110 mg/dL
• Low-Density Lipoprotein Cholesterol (LDL-C): 120 mg/dL

Simple math shows a non-HDL cholesterol of 200 – 50 = 150 mg/dL. This number gives us a better predictor of heart disease risk from a regular cholesterol test than LDL-cholesterol alone. For individuals who are generally healthy, a non-HDL cholesterol less than 130 mg/dL is a reasonable goal. There is further benefit at even lower levels, and there is no blood level that is “too low”. Recall that our cells can make all the cholesterol that they need for themselves, without relying on high levels to be delivered from the blood.

For individuals who are at high risk for heart disease (for example, those with certain genetic conditions or who have already had heart disease problems like a heart attack), the goal is to get this non-HDL cholesterol level as low as possible. A particularly risky situation is when the cholesterol panel shows a high LDL-C, a high triglyceride level, and low HDL-C. This is often seen in people with diabetes and other conditions that significantly increase the risk of heart disease.

An even better test involves measuring the actual number of lipoproteins rather than the amount of cholesterol they carry, as is done on the basic cholesterol test. This is called an Apolipoprotein B measurement, abbreviated as ApoB. It provides a superior measure of heart disease risk, but many doctors are still unfamiliar with it and may be reluctant to order it. ^{[Sniderman 2021]} Hopefully this changes in the future, since it is not a very complex or expensive blood test to perform and provides even better information.

There is a lot more to interpreting blood cholesterol tests but we will use this approach for now. There are many other tests that can be performed beyond the basic cholesterol panel and apolipoprotein B measurement, but most of them do not provide much added value for predicting risk beyond what has been discussed here.

In part 2 we will discuss what should be done when your blood cholesterol levels are high, before moving on to address myths and misconceptions.

Thank you to Tom Campitelli, DTFP, for his assistance in editing this article.