The Impact of LDL Cholesterol Particle Size and ApoB on Heart Health

According to the Centers for Disease Control and Prevention (CDC), an estimated 80% of cardiovascular disease—which includes heart disease and stroke—are preventable. [1] As such, InsideTracker has always measured key blood biomarkers associated with heart health, like various cholesterol particles. But since the research is always being updated, we're always looking to do the same to our system and the biomarkers we test. So, we sought out to evaluate two components of cholesterol particles getting a lot of attention: particle size and concentration of Apolipoprotein B. We found that, though recent findings suggest there may be a relationship between particle size heart disease risk, the evidence is not yet conclusive. For ApoB, the research is more conclusive and indicates that it is a good predictor of heart health.  



Biomarkers related to heart health and longevity

InsideTracker users are familiar with what we call the Lipid Group—a family of biomarkers related to heart health which currently includes LDL , HDL, total cholesterol, and triglycerides (tip: if you want to learn about or need a quick refresher on these markers, check out this blog). Cholesterol is necessary in certain amounts, as it plays an important role in vital body functions such as forming cell membranes and synthesizing hormones and vitamins. But as you may know, excessively high levels of circulating cholesterol in the blood can contribute to the progression of heart disease.



Lipid Group biomarkers aren't the only ones related to heart health. InsideTracker also tests a protein called hsCRP that rises and falls in response to inflammation levels, providing a reliable depiction of full-body inflammation. Elevated levels of this marker can help to predict an individual's risk for cardiovascular disease. [2]

Monitoring and optimizing biomarkers related to cardiovascular disease risk can play an important role in positively influencing our biological age, thus extending our healthspan.

But what about lipid particle size and Apolipoprotein B?

Recently, researchers and biohackers alike have taken an interest in the characteristics of certain lipid particles, like LDL cholesterol. Interestingly, these particles can actually vary in their size and compositions of the cargo they carry. Scientists have postulated that these differences can have differential impacts on health. As science continues to evolve, the Science Team at InsideTracker is continuously looking for scientifically-proven and safe ways to help our users optimize their health—so we decided to explore these complexities that have piqued the interest of many in the health community. 

Based on current research, Apolipoprotein B has emerged as the superior marker for assessing cardiovascular disease risk. LDL particle size also has quality evidence behind it, but as it’s a metric that’s not yet as standardized nor as strongly predictive as ApoB, ApoB remains a better assessment of heart health than LDL particle size alone.

What we know about the impact of LDL particle size on heart health

LDL cholesterol is particularly troublesome due to its capacity to oxidize. Oxidized particles are more likely to become implanted in blood vessels and harden in a process known as atherosclerosis. This process can be extremely detrimental to heart health and can even cause blockages in the arteries. This is where LDL-P comes into play.

According to InsideTracker’s lead nutrition scientist Ashley Reaver, smaller LDL particles can become lodged in the arteries more easily, while the larger LDL particles appear to be less dangerous. But while the science behind LDL particle size is promising, it should not yet be used to determine and manage someone's risk of cardiovascular disease (CVD).[3] 

It's important to note that elevated levels of small LDL particles have been reported in many conditions related to poor heart health, including low HDL, obesity, insulin resistance, diabetes, and metabolic syndrome. [4,5,6] But while some studies suggest an association between small, dense LDL particles and atherosclerosis, other studies demonstrate that this association is not significant after adjustments for lipid and non-lipid risk factors such as triglyceride and HDLcholesterol levels. [7,8]



One prospective nested case-control study of 230 healthy middle-aged women found that the measure LDL particle size was not a more powerful predictor of CVD risk than total-cholesterol-to-HDL ratio and was less powerful than C-reactive protein (CRP) measures. [7] Another nested case-control prospective study of 1,885 middle-aged healthy men and women found that the predictive power of LDL-P for CVD risk was comparable to that of non-HDL cholesterol levels and was no longer a significant predictor of heart disease risk once adjusted for HDL and triglyceride levels. [4]

• Testing methods for lipid particle size are not yet standardized, whereas ApoB testing is.
• Lipid composition and size can be subject to genetics [9]

Even though LDL particle size is a better predictor than the normally tested LDL cholesterol the precision at which the LDL particle size can predict cardiovascular disease risk independent of lipid and non-lipid risk factors continues to be unclear

Apolipoprotein B is a proxy for LDL particle number

In clinical assays and blood tests like InsideTracker, LDL cholesterol is typically measured in a concentration, meaning it's assessed per unit of blood volume and not as an absolute particle count. However, recent research has postulated that using an absolute count of LDL particles in the blood, also known as LDL particle number, may be a more appropriate and reliable assessment method for measuring LDL cholesterol and its association with heart disease risk. Proponents of this change have recommended measuring Apolipoprotein B (ApoB) as a proxy for particle number, as ApoB is a protein on the surface of all potentially atherogenic particles, and present in a 1:1 ratio with these particles to provide a direct measurement. [10,11]

Preliminary findings suggest that ApoB concentration may be an appropriate metric for evaluating LDL particle number, and many studies even show it to be far better at predicting future CVD events than LDL cholesterol. [11]. 

InsideTracker's approach to LDL-P 

While the emerging science behind these markers has the potential to increase the accuracy of determining an individual’s risk for CVD there is not currently enough research to determine an optimal zone or specific recommendations to be developed for particle size, which are both necessary for a biomarker to join the InsideTracker platform. Because of the continued need for further research, InsideTracker does not include LDL particle size or number in our lipid panels just yet. To learn more about the process behind how we select the biomarkers we test, check out this article.

Actionable steps to improve your heart health:

Does it still feel challenging for you to improve your heart health? Read these stories of these InsideTracker users who improved their heart health at a young age for some inspiration.

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