What Is Lipoprotein(a) and Why Does It Matter?

Lipoprotein(a) is a type of lipoprotein particle that's structurally similar to LDL cholesterol ("bad cholesterol") but carries an additional protein called apolipoprotein(a), or apo(a). This structural add-on gives Lp(a) unique biological properties and makes it more atherogenic (artery-damaging) than LDL alone.

Elevated Lp(a) is an independent and genetically determined risk factor for atherosclerotic cardiovascular disease, including heart attack, stroke, and aortic valve stenosis.¹ ²

Lp(a) levels are approximately 70–90% genetically determined and remain relatively stable throughout life.³ This makes Lp(a) a unique and important marker for assessing inherited cardiovascular risk.

According to the American College of Cardiology and American Heart Association (ACC/AHA), an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L) is considered elevated and associated with increased cardiovascular risk.⁴

The Challenge: Why Lp(a) Is Difficult to Measure Consistently

1. Extreme Size Variability (Isoform Heterogeneity)

According to the National Heart, Lung, and Blood Institute (NHLBI):

"Apo(a) contains a variable number of structural motifs called 'kringles', which give rise to more than 40 different Lp(a) isoforms leading to very heterogeneous and complex Lp(a) particles. Accurate and reliable measurement of Lp(a) is challenging due to its complex and heterogeneous structure, and represents an important gap in the field."⁵

Furthermore, most individuals inherit two different LPA genes (one from each parent), meaning they express two different apo(a) isoforms simultaneously, adding another layer of complexity.⁶

2. Assay Sensitivity to Isoform Size

Different laboratory assays respond differently to these size variations. Some assays are "isoform-sensitive," meaning they may underestimate Lp(a) in individuals with small apo(a) isoforms (who typically have higher Lp(a) levels) and overestimate Lp(a) in those with large isoforms (who typically have lower levels).⁷

The American Heart Association's 2022 Scientific Statement confirms:

"The first problem, related to the size variability of apo(a), results in under- or overestimation of Lp(a) levels measured by different immunoassays."²

3. Significant Inter-Laboratory Variation

A 2025 study published by the Centers for Disease Control and Prevention (CDC) examined Lp(a) measurements across multiple clinical laboratories and found striking differences:

"Lp(a) interassay measurement variations ranged from 3.3% to 69.1% across individual samples."⁸

This means that for some individuals, one laboratory might report a result nearly 70% different from another laboratory, even when testing the same individual, within a short period of time.

4. Lack of Universal Standardization

The American College of Cardiology notes:

"Because of Kringle IV type-2 repeat polymorphism of the lipoprotein(a) (LPA) gene that codes for Apo(a), there is a wide variability in Lp(a) size in the population... For years, this correlation posed a challenge in developing standard assays for Lp(a) quantification."⁴

A previous WHO/IFCC reference material (SRM-2B) has been depleted, and a new reference measurement system is still being established.⁸ ⁹

5. Different Units of Measurement

Adding to the confusion, Lp(a) can be reported in two different units:

• mg/dL (milligrams per deciliter): measures mass concentration
• nmol/L (nanomoles per liter): measures particle number

There is no accurate universal conversion factor between these units because the conversion depends on the individual's specific apo(a) isoform size. Using a standard conversion factor (such as 2.5) can introduce significant error.⁴ Guidelines strongly advise interpreting Lp(a) in the same unit in which it was measured.

How HealthieOne Addresses These Challenges

At HealthieOne, we understand the complexities of Lp(a) measurement and have implemented rigorous methodologies to provide the most accurate and sensitive results possible.

How Newer Methods Try to Improve Accuracy: Mass-Spectrometry–Based Approaches (LC-MS/MS)

Emerging reference methods based on liquid chromatography–tandem mass spectrometry (LC-MS/MS) aim to:

• Quantify Lp(a) components based on mass/charge rather than antibody binding
• Reduce isoform-related bias inherent in many immunoassays

These methods are currently more common in specialized or reference laboratories and have been recognized by the IFCC Working Group for Apolipoproteins as a candidate reference measurement procedure for Lp(a) standardization.⁸ ⁹

6-Point Calibration Protocol

To ensure accuracy across the full range of Lp(a) concentrations and isoform sizes, we employ a 6-point calibration protocol. This multi-point approach helps minimize measurement bias that can occur with simpler calibration methods, particularly at the extremes of the measurement range.

A Scientific Statement from the American Heart Association: “the use of 5 independent calibrators with a large range of Lp(a) levels and a suitable distribution of apo(a) isoforms are able to quantify Lp(a) with a reduced impact of apo(a) size if the values of the assay calibrators are well validated."²

What This Means for Your Results

Because our methodology is highly sensitive, HealthieOne results may appear higher than results from laboratories using less sensitive traditional immunoassays. This doesn't mean either result is "wrong", it reflects the different capabilities of the testing methods.

What Should You Do If Your Results Differ Between Labs?

1. Don't Panic: Focus on the Clinical Picture

If you receive different Lp(a) values from different laboratories, the most important question is: Do both results lead to the same clinical interpretation?

For example:

• If Lab A reports 17 mg/dL (normal) and Lab B reports 32 mg/dL (high-normal), both suggest your Lp(a) is not in the high-risk category (>50 mg/dL).
• If Lab A reports 45 mg/dL (borderline) and Lab B reports 85 mg/dL (elevated), both suggest you should discuss cardiovascular risk management with your physician.

2. Use the Same Laboratory for Trend Monitoring

Because of inter-laboratory variability, clinical guidelines recommend using the same laboratory and methodology when tracking Lp(a) over time. This ensures that any changes you observe reflect true biological changes rather than methodological differences.¹ 

3. Understand That Lp(a) Is Genetically Stable

In most adults, Lp(a):

• Is remarkably stable over time.³ 
• Does not change much with diet, exercise, or most standard lipid-lowering drugs, unless you have kidney disease, significant inflammation, advanced liver disease, hypothyroidism, hyperthyroidism, postmenopausal hormone replacement, growth hormone therapy, pregnancy, or are on Lp(a)-lowering therapies.⁴

4. Discuss Results with Your Healthcare Provider

Share all your Lp(a) results with your physician, along with information about which laboratory performed each test. This context helps your provider interpret the results appropriately and make informed recommendations about your cardiovascular health.

References

1. Cleveland Clinic Journal of Medicine. November 2025, 92 (11) 679-685. Lipoprotein(a) in clinical practice: What clinicians need to know. 
2. American Heart Association. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology. 2022. 
3. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. European Heart Journal. 2022. 
4. American College of Cardiology. An Update on Lipoprotein(a): The Latest on Testing, Treatment, and Guideline Recommendations. September 2023. 
5. National Heart, Lung, and Blood Institute. Standardization for Lipoprotein(a) Measurement in Humans. 2019. 
6. Kronenberg F. The ins and outs of lipoprotein(a) assay methods. Journal of Lipid Research. 2024. 
7. Kronenberg F. Lipoprotein(a) measurement issues: Are we making a mountain out of a molehill? Atherosclerosis. 2022;349:123-135. 
8. Lyle AN, et al. Interlaboratory comparison of serum lipoprotein(a) analytical results across clinical assays—Steps toward standardization. Journal of Clinical Lipidology. 2025. 
9. Nina M. Diederiks et al. 2023. Developing an SI-traceable Lp(a) reference measurement system: a pilgrimage to selective and accurate apo(a) quantification 

This article is for educational purposes only and should not replace professional medical advice. Please consult with your healthcare provider to interpret your Lp(a) results and discuss your individual cardiovascular risk.