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Part 2- All about LDL Cholesterol
In part 1 we looked at why we care about blood levels of cholesterol, and we learned what is included in the standard cholesterol test many people get at their annual physical. Here we will examine LDL cholesterol more closely to learn what this number tells us about risk of heart disease or stroke, as well as some of its limitations.
LDL cholesterol is the number that is most commonly used to estimate cardiovascular risk. It is the particle in our bloodstream that carries the most cholesterol, and countless studies have shown without a doubt that LDL cholesterol causes cardiovascular disease. In addition, most studies that have tested the effectiveness of various cholesterol lowering treatments have used LDL cholesterol as the primary treatment target. LDL cholesterol should be considered a waste product, and there is no beneficial role of having LDL cholesterol in our bloodstream.
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While there is a constant movement of cholesterol into and out of the
lining of our arteries, the net accumulation of cholesterol in the artery appears to occur at LDL cholesterol levels much lower than the average levels of 120-130 mg/dL seen in the population. As a result, for the highest risk patients, it is recommended to lower LDL cholesterol to at least <70 mg/dL, with some organizations suggesting even more aggressive treatment. Reassuringly, there is no known level of LDL cholesterol that is "too low". People who are fortunate to have genetic conditions leading to lifelong levels of LDL cholesterol that are extremely low do not have any negative health consequences (and as you could probably guess, they do not develop cardiovascular disease either). What about lowering LDL cholesterol with medication instead of from genetics? Thankfully there are several research studies that have tested patients with very low levels of LDL cholesterol due to medications- and these people do not have any negative health consequences either! So we can feel confident in following the adage "lower is better".
The concept of "lower is better" sounds good, but let's try to be a little more specific... Based on research performed on more than 100,000 patients, it turns out that over a 5 year period, for every drop of LDL cholesterol by 39 mg/dL, your risk of a major cardiovascular event (like heart attack, stroke, or dying from these) goes down by about 20%. And the effect is additive, meaning that if you start with an LDL cholesterol of 150 mg/dL and drop it to 72 mg/dL- your risk of major cardiovascular events over 5 years goes down by 40%! But wait...there's more! Those are just the benefits over the first 5 years. Considering that cardiovascular disease results from lifetime exposure to cholesterol particles, your life-long reduction of risk will be even more than the initial 40%.
If it sounds too good to be true, it's not. Or at least it's mostly not. There are a few ways we can be fooled when we are only looking at the LDL cholesterol reported on a standard lipid panel. Let's take a look at a couple of these:
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As we looked at before, the value of LDL cholesterol is most commonly calculated based on other measurements. Luckily, this calculation usually gets us pretty close to the actual value. However, in people with very high or very low levels of LDL cholesterol, and/or for people who have high triglyceride levels- the calculation is unreliable and the LDL cholesterol must be directly measured. This test usually doesn't happen automatically and needs to be ordered by your doctor.
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Calculating or measuring the amount of cholesterol in your LDL particles gives you no information about the actual number of particles that are floating around. Recall the example of the balloons from part 1. Risk of heart attacks and strokes tracks more closely with the number of particles, and at least 10-20% of people have particle numbers that are higher or lower than would be predicted based on the cholesterol level alone.
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By focusing only on LDL cholesterol we can easily overlook the other cholesterol carrying particles that are floating around in the bloodstream which are also contributing to your risk of heart attack or stroke.
LDL cholesterol is a reasonably good place to start when we want to learn about a person's risk of cardiovascular disease. However, as outlined above, it is not a perfect test and if we overly rely on LDL cholesterol we can be tricked, leading us to underestimate or overestimate a person's risk. In Part 3 we will look at some of the ways to overcome the shortcomings of LDL cholesterol to help us get a more complete picture.