A New Understanding of Cardiovascular Risk
For decades, GPs have primarily relied on standard lipid panels—especially LDL cholesterol—to gauge heart disease risk. However, a growing body of research indicates that apolipoprotein B100 (apoB100) can provide a more detailed and accurate view of cardiovascular health. By assessing the total number of atherogenic particles in circulation, apoB100 uncovers hidden risk that LDL cholesterol tests can miss.
About ApoB100
ApoB100 is a structural protein found on all atherogenic lipoproteins—LDL, VLDL, and lipoprotein(a). Notably, each lipoprotein particle carries exactly one molecule of apoB100. This “1:1” relationship transforms apoB100 into a direct lipoprotein particle counter, showing how many plaque-forming particles are circulating, not just how much cholesterol is inside them.
Why ApoB100 Outperforms LDL Cholesterol as a biomarker
Large-scale studies consistently demonstrate that apoB100 is a better predictor of cardiovascular events, such as heart attacks and strokes, than LDL cholesterol. ApoB100:
- Captures All Atherogenic Lipoproteins: LDL cholesterol measures the cholesterol content within lipoprotein particles, while apoB100 measures the total number of particles.
- Reveals Hidden Risk: Some individuals with “normal” LDL levels may still harbor a high number of atherogenic particles, reflected in elevated apoB100.
- Guides Tailored Therapy: Knowing the total atherogenic particle count helps physicians decide if lifestyle changes suffice or if more aggressive measures, like medication, are warranted.
The difference between measuring particle number versus cholesterol content is crucial for understanding cardiovascular risk. Traditional cholesterol tests measure the total amount of cholesterol within LDL particles, but this approach can mask important variations in risk. LDL particles in the bloodstream aren't uniform - they can vary significantly in both size and density. Some individuals have relatively few but large LDL particles, each carrying more cholesterol, while others have many small, dense particles, each carrying less cholesterol. This means two people could have identical LDL cholesterol readings but very different numbers of particles circulating in their blood.
This distinction matters because small, dense LDL particles are particularly dangerous. Their size and density make them more likely to penetrate artery walls, where they can initiate or contribute to plaque formation. Each individual particle, regardless of how much cholesterol it carries, has the potential to enter the artery wall and contribute to atherosclerosis. Therefore, having a greater number of particles - even if they individually carry less cholesterol - can indicate higher cardiovascular risk.
This is where apoB100 measurement provides crucial additional information. Every atherogenic particle, whether large or small, carries exactly one apoB100 molecule. By measuring apoB100, we get a direct count of the number of potentially harmful particles circulating in the bloodstream, regardless of their size or how much cholesterol each carries. This provides a more accurate assessment of cardiovascular risk than simply measuring the total amount of cholesterol being transported.
The practical implication is significant: two individuals with the same LDL cholesterol level might have very different numbers of particles capable of causing arterial damage. ApoB100 measurement reveals this hidden risk by counting the actual number of particles rather than just their collective cholesterol cargo..
The APOB Gene and Genetic Differences
Now, it is important to note that apoB100 is encoded by the APOB gene. Like many other genes, APOB can exhibit small, naturally occurring variations in its DNA sequence among different individuals. These genetic differences—or polymorphisms—can subtly alter how the gene functions and, in turn, how much apoB100 the body produces or how effectively it operates.
One such polymorphism is a single nucleotide polymorphism (SNP) known as rs693. In this case, a change at a specific position in the APOB gene can affect the production of the apoB100 protein. This variation can ultimately influence an individual’s baseline lipid levels and overall cardiovascular risk.
How the rs693 SNP Influences ApoB100
The rs693 SNP (also referred to as the XbaI polymorphism) can be inherited in three different forms (genotypes):
A/A: Associated with elevated apoB levels and an adverse lipid profile (higher LDL, total cholesterol, and total lipids, with lower HDL), marking the A allele as the risk allele.
G/A: Shows an intermediate effect on apoB levels and lipid parameters.
G/G: Typically linked with a more favorable profile, with lower apoB levels and reduced lipid abnormalities.
These genetic differences may cause two people with the same lifestyle to have significantly different apoB100 levels. Consequently, those carrying the A/A genotype may be predisposed to accumulating more atherogenic particles over time, even if initial blood tests do not appear alarming.
The ApoB rs693 SNP is reported under Mygene’s Cardiovascular Panel under the LDL Transport and Familial Hyperholesteromia Traits.
Combining both ApoB100 Levels and rs693 Genotype
ApoB100 levels reflect the current status of circulating atherogenic particles—a real-time snapshot of your cardiovascular risk. The rs693 genotype, on the other hand, provides clues about your long-term or inherent predisposition to produce higher or lower levels of apoB100. Together, these two pieces of information allow for:
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Early Detection of Underlying Risk
Even if you have a borderline apoB100 level now, a high-risk genotype (A/A) signals that levels could climb more easily.
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Tailored Treatment Approaches
Individuals with low apoB100 and the G/G genotype may do well with lifestyle modifications alone, while those with high apoB100 and the A/A genotype may need earlier or more intensive pharmacotherapy.
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Improved Prediction of Future Changes
Genetic factors can hint at whether apoB100 might remain stable or rise over time, guiding preventative measures proactively.
Clinical Risk Assessment
While various practice guidelines are still evolving, many clinicians use the following thresholds for apoB100:
Optimal: < 0.8 g/L
Borderline: 0.8–1.0 g/L
High: > 1.0 g/L
Very High: > 1.2 g/L
When combined with rs693 testing, these cutoffs become more precise:
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Low Risk Profile
- ApoB100 < 0.8 g/L AND G/G genotype
- Recommendation: Maintain a healthy lifestyle (balanced diet, regular exercise)
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Moderate Risk Profile
- ApoB100 0.8–1.0 g/L OR G/A genotype with ApoB100 < 1.0 g/L
- Recommendation: Intensify lifestyle measures; consider pharmacotherapy if risk factors like hypertension or diabetes are present
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High Risk Profile
- ApoB100 > 1.0 g/L OR A/A genotype with ApoB100 > 0.8 g/L
- Recommendation: Pharmacological intervention (e.g., statins, PCSK9 inhibitors), alongside targeted lifestyle optimizations
Real-World Applications
Combining apoB100 measurement and rs693 genotyping helps clinicians:
- Identify High-Risk Individuals Earlier
- Individuals with the A/A genotype may warrant closer monitoring or earlier therapy to prevent disease progression.
- Improve Risk Stratification
- Two patients with the same LDL value might have very different apoB100 and genetic predispositions, leading to distinct treatment paths.
- Treatment can be escalated or de-escalated based on a more accurate evaluation of both current and genetic risk.
Implementation in Australian Practice
In Australia, standard lipid testing is typically covered under Medicare, but coverage for apoB100 and genetic tests varies. Mygene strongly recommends use of apoB100 plus rs693 testing for:
- Individuals with a family history of premature heart disease
- Patients whose lipid panels do not match their clinical presentation
- People who have multiple cardiovascular risk factors (e.g., smoking, diabetes, hypertension)
Future Directions
Ongoing research aims to integrate additional genetic markers and inflammatory indicators (like high-sensitivity CRP) alongside apoB100. By delving into a broader suite of biomarkers and genetic variants, clinicians hope to develop even more personalized cardiovascular risk profiles, guiding preventative strategies and therapies with unprecedented accuracy.
Take Home Message: Measuring apoB100 quantifies how many atherogenic particles you have right now, while rs693 helps predict how your apoB100 levels may evolve over time. Used together, they form a powerful tool for preventing heart disease before it strikes.