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Interpreting Your Test
Part 3- Moving Beyond LDL Cholesterol
In Part 1 we discussed the purpose of measuring blood levels of cholesterol- namely, to attempt to predict a person’s risk of future disease such as heart attack or stroke. In Part 2 we took a more in depth look at LDL cholesterol (also referred to as LDL-c), seeing that it is clearly linked in a causal way with cardiovascular disease. While LDL-c is a decent prediction tool, we looked at several ways in which LDL-c can be misleading- either overestimating or underestimating one’s risk. We need to do better than that! Thankfully there are easy ways to refine our risk models and here, in part 3, we will examine some ways to do so.
Recall that there are significant ways in which relying only on LDL-c can lead to incorrect risk prediction. The most significant examples are : 1) If the calculated value of LDL cholesterol is substantially different from the “actual” value. 2) If the number of LDL particles is incorrectly represented by only measuring the cholesterol content within them. 3) Ignoring other particles that cause disease, such as VLDL.
Fortunately, there are additional tests that are available to help fill in some of the gaps and help us feel more confident in our risk estimate. Let’s take a look at a couple common ones:
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LDL-direct: This test measures the cholesterol content of all the LDL particles in a specified amount of blood, rather than relying on a mathematical calculation to give us a ballpark figure. It is useful to know in people have conditions that make the standard calculation unreliable, and is most commonly ordered if a person’s triglycerides are elevated. It avoids problem #1 outlined above, but unfortunately does nothing to address problems #2 or #3.
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LDL-p: LDL-p (the p stands for “particle”) is a way to count the actual number of LDL particles that are present in the blood. Remember, a person’s risk tracks more closely with the number of particles floating around rather than the amount of cholesterol contained within them. So, counting up the particles rather than weighing the cholesterol in them can give us a more reliable way to assess risk compared to LDL-c- avoiding problems #1 and #2 above. But we’re still left with the problem of how to account for the particles that cause problems in addition to LDL…
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Non-HDL Cholesterol: This number gives us the amount of cholesterol contained in all of the particles in your blood, with the exception of HDL. The idea here is that HDL particles do not get stuck in the artery walls and thus do not cause vascular disease, but all of the other particles can. So knowing the amount of cholesterol in all of the disease causing particles can help improve risk estimation. The convenient thing about this measurement is that it can be calculated from the information obtained from a standard lipid panel- it is simply the total cholesterol minus the HDL cholesterol. By utilizing non-HDL cholesterol instead of LDL-c we get around problem #3 above. So we’re getting closer, but we are still using cholesterol content to estimate the numbers of particles…so it doesn't address problem #2 above.
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Apo B: Luckily, nature has provided us with a clever solution called Apo B (also known as Apo B100, Apolipoprotein B, Apolipoprotein B100). Apo B is a protein that provides structure to lipoprotein particles such as LDL or VLDL. It is not present on HDL. And, as luck would have it, there happens to be exactly 1 copy of Apo B sitting on every dangerous particle in your blood stream (see the drawing here, adapted from nebula.org). So, if we know how much Apo B is floating around, we also know how many dangerous particles are there as well!
So what can we make of all this? I tend to think of things in the framework of good, better, best. Knowing someone’s LDL cholesterol level is good. It allows for a risk prediction that is vastly superior to what can be accomplished without knowing their LDLc. However, due to the issues we outlined above, LDL-p and non-HDL cholesterol are better, and can give us additional, more refined, information. These measurements are particularly useful in patients who we know are likely to face inaccurate risk estimation by using LDLc alone, such as those with diabetes and/or metabolic syndrome. That leaves us with “best”- which is Apo B. This is the most complete test- by revealing the number of all of the dangerous particles. It also provides a useful metric to follow as we initiate treatments, both lifestyle changes as well as medications.
This all can be a little overwhelming, but the single most important message I would like you to take away from the discussion is this: Make it a priority to understand your risk… just start somewhere! Depending on your particular health situation it may be useful to go beyond the standard lipid profile. So please discuss with your primary care physician or your lipid specialist whether additional testing is appropriate.