Lipoprotein(a), An Overlooked Marker of Cardiovascular Risk

Written By Sam Hetz

Cardiovascular disease remains the leading cause of death globally. Most screening focuses on traditional risk factors such as LDL cholesterol, blood pressure, diabetes, and smoking. However, another important biomarker is increasingly recognized for its role in cardiovascular risk: lipoprotein(a), often abbreviated Lp(a).

Many individuals with otherwise normal cholesterol profiles may still carry elevated cardiovascular risk due to high Lp(a) levels. New long term research provides further evidence that this biomarker may play a meaningful role in cardiovascular prevention.

What Is Lipoprotein(a)?

Lipoprotein(a) is a cholesterol carrying particle structurally similar to LDL cholesterol. The key difference is the presence of an additional protein called apolipoprotein(a) that binds to the LDL particle.

This structural feature gives Lp(a) several properties associated with cardiovascular disease:

  • Promotion of atherosclerosis through cholesterol deposition in arterial walls

  • Contribution to vascular inflammation

  • Increased potential for thrombosis, due to structural similarity with plasminogen

Unlike many other cardiovascular risk factors, Lp(a) levels are largely genetically determined. Approximately 80 percent to 90 percent of circulating levels are inherited, meaning lifestyle interventions such as diet and exercise have minimal effect on the concentration of Lp(a) in the bloodstream.

Lp(a) levels are also stable across the lifespan, which means that a single measurement is generally sufficient to estimate long term risk.

New Evidence From a 30 Year Cohort Study

A large prospective cohort study from the Women’s Health Study recently evaluated how baseline Lp(a) levels relate to cardiovascular outcomes over long term follow up.

The study included 27,748 healthy women without known cardiovascular disease at baseline and followed participants for a median of 27.8 years.

Researchers examined the relationship between Lp(a) levels and several outcomes:

  • Major cardiovascular events

  • Coronary heart disease

  • Ischemic stroke

  • Cardiovascular death

Key Findings

Risk increased progressively with rising Lp(a) levels.

Two clinically relevant thresholds emerged.

Lp(a) greater than 30 mg/dL (approximately the 75th percentile)

Associated with increased risk of:

  • Major cardiovascular events

  • Coronary heart disease

Lp(a) greater than 120 mg/dL (approximately the 99th percentile)

Associated with increased risk of:

  • Ischemic stroke

  • Cardiovascular death

Compared with women with Lp(a) levels below 10 mg/dL, those with levels above 120 mg/dL had:

  • 54 percent higher risk of major cardiovascular events

  • 80 percent higher risk of coronary heart disease

  • 63 percent higher risk of cardiovascular death

These findings reinforce that very high Lp(a) levels represent a meaningful and persistent cardiovascular risk factor, even in otherwise healthy individuals.

Why Lipoprotein(a) Is Often Missed

Most standard lipid panels measure:

  • Total cholesterol

  • LDL cholesterol

  • HDL cholesterol

  • Triglycerides

Lp(a) is not included in routine lipid testing and must be ordered separately.

Because of this, many individuals with elevated levels remain unaware of the risk. This is particularly important because people with normal LDL cholesterol may still carry increased cardiovascular risk if Lp(a) is elevated.

Who Should Consider Testing?

Several cardiology societies recommend measuring Lp(a) at least once in adulthood, particularly in individuals with elevated cardiovascular risk.

Testing may be helpful in individuals with:

  • Family history of premature cardiovascular disease

  • Unexplained early heart attack or stroke

  • Persistently elevated LDL cholesterol despite therapy

  • Personal or family history of genetic lipid disorders

Because Lp(a) is genetically determined and stable over time, a single test can often provide lifetime risk information.

Treatment and Management

At present, therapies specifically designed to lower Lp(a) are still under investigation. Several RNA based therapies targeting Lp(a) production have shown promising results in early clinical trials and may become available in the coming years.

For individuals with elevated Lp(a), current management focuses on aggressive control of modifiable cardiovascular risk factors, including:

  • Optimizing LDL cholesterol levels

  • Blood pressure management

  • Smoking cessation

  • Exercise and metabolic health

  • Weight management

Reducing overall cardiovascular risk becomes especially important in individuals with genetically elevated Lp(a).

The Future of Cardiovascular Prevention

Preventive cardiology is increasingly moving toward precision risk stratification, where genetics and biomarkers help identify individuals at higher risk earlier in life.

Lipoprotein(a) represents one of the most important emerging markers in this space.

As evidence continues to accumulate, Lp(a) screening may become a more routine component of comprehensive cardiovascular risk assessment, helping identify individuals who may benefit from earlier and more targeted prevention strategies.

References

Nordestgaard AT, Chasman DI, Moorthy V, et al.
Thirty-Year Risk of Cardiovascular Disease Among Healthy Women According to Clinical Thresholds of Lipoprotein(a).
JAMA Cardiology. Published online January 7, 2026. doi:10.1001/jamacardio.2025.5043.

Tsimikas S.
A Test in Context: Lipoprotein(a).
Journal of the American College of Cardiology. 2017;69(6):692 to 711. doi:10.1016/j.jacc.2016.11.042.

Mach F, Baigent C, Catapano AL, et al.
2023 ESC Guidelines for the management of dyslipidaemias.
European Heart Journal. 2023;44(39):3817 to 3893. doi:10.1093/eurheartj/ehad192.

Wilson DP, Jacobson TA, Jones PH, et al.
Use of Lipoprotein(a) in Clinical Practice: A Biomarker Whose Time Has Come.
Journal of Clinical Lipidology. 2019;13(3):374 to 392. doi:10.1016/j.jacl.2019.04.010.

Burgess S, Ference BA, Staley JR, et al.
Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a) Lowering Therapies.
JAMA Cardiology. 2018;3(7):619 to 627. doi:10.1001/jamacardio.2018.1470.

O’Donoghue ML, Fazio S, Giugliano RP, et al.
Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk.
Circulation. 2019;139(12):1483 to 1492. doi:10.1161/CIRCULATIONAHA.118.037184.

Sam Hetz
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