Lipoprotein(a), or Lp(a), is emerging as an important but often overlooked factor in cardiovascular disease (CVD) risk. Elevated Lp(a) is common. An estimated 1.4 billion people worldwide have high Lp(a) (≥50 mg/dL), roughly 10 to 30% of the global population. Unlike LDL cholesterol, Lp(a) has historically been under-recognized in conventional practice, in part because routine guidelines did not emphasize it and no dedicated treatment was available. However, research now confirms that high Lp(a) is a genetic, independent risk factor for atherosclerosis and heart disease. Functional medicine practitioners are in a unique position to identify elevated Lp(a) and address its risks through a personalized, holistic approach. This article explains what Lp(a) is, why it matters for CVD, and how to address it using a functional medicine lens.

What Is Lp(a)?

Lp(a) is often described as “LDL on steroids.” Structurally, an Lp(a) particle is an LDL particle with an extra protein, apolipoprotein(a), attached by a disulfide bond. Apo(a) is a distinctive protein that resembles plasminogen (the blood’s clot-dissolving protein), giving Lp(a) some unique properties. Because of the apo(a) component, Lp(a) is more atherogenic than LDL on a per-particle basis. The apo(a) tail carries inflammatory oxidized phospholipids and can interfere with fibrinolysis (clot breakdown), promoting plaque buildup and clot formation.

Prevalence and Genetics

Elevated Lp(a) (often defined as >50 mg/dL or about >125 nmol/L) is found in roughly 20% of Caucasians and up to 30% or more of certain ethnic groups. Individuals of African descent tend to have 2 to 3 times higher Lp(a) levels than those of European descent. Lp(a) is primarily genetic and follows an autosomal codominant inheritance pattern. In fact, more than 90% of the variation in Lp(a) levels is determined by the LPA gene. Most people inherit two different versions of the gene, and smaller apo(a) isoforms result in higher Lp(a) concentrations. Lp(a) levels are remarkably stable over a lifetime and are not significantly influenced by lifestyle.

Lp(a) and Cardiovascular Risk

High Lp(a) is associated with accelerated atherosclerosis and a higher incidence of heart attacks, strokes, and peripheral artery disease. Mendelian randomization studies show that genetic variants that raise Lp(a) also raise the risk of coronary disease, implying Lp(a) is a causal contributor to CVD. An Lp(a) level above approximately 50 mg/dL (125 nmol/L) can increase ASCVD risk by about 40%, and extremely high levels may double or triple the risk.

Lp(a) also contributes to calcific aortic valve disease and ischemic stroke, especially in younger patients. It interferes with fibrinolysis, adding a thrombosis risk on top of plaque buildup. The 2018 ACC/AHA cholesterol guidelines list elevated Lp(a) as a “risk enhancer,” suggesting more aggressive preventive strategies should be considered.

Testing

Who and when to test: Expert panels suggest a one-time Lp(a) test for all adults, especially in those with a family history of premature ASCVD or unexplained early heart disease.

How to test and interpret: Lp(a) can be measured in mass concentration (mg/dL) or particle concentration (nmol/L). Most experts favor nmol/L (particle count) using isoform-insensitive assays.

• Optimal/low-risk: <30 mg/dL (75 nmol/L)
• Intermediate: 30 to 50 mg/dL (75 to 125 nmol/L)
• High-risk: ≥50 mg/dL (≥125 nmol/L)

Lp(a) interpretation sits alongside ApoB, particle number, and the rest of the advanced lipid panel. Our advanced lipid testing course for clinicians works through these markers together, including how to act on discordant results.

Treatment

Treating high Lp(a) is challenging because it is largely genetic. Most conventional lipid-lowering drugs have little to no impact on Lp(a), and statins may even increase it slightly.

• PCSK9 inhibitors can reduce Lp(a) by about 20 to 30%.
• Lipoprotein apheresis reduces Lp(a) by 30 to 70% but is invasive and costly.

Emerging Therapies

Several new therapies are being developed specifically to target Lp(a). Two of the most advanced are pelacarsen, an antisense oligonucleotide, and olpasiran, a small interfering RNA. Both work by targeting apolipoprotein(a) messenger RNA in the liver to reduce apo(a) production.

In phase 2 testing, pelacarsen reduced Lp(a) by approximately 80%, and olpasiran at doses of 75 mg or higher every 12 weeks reduced Lp(a) by more than 95% at week 36. Both are now in phase 3 cardiovascular outcomes trials: Lp(a)HORIZON for pelacarsen (NCT04023552, more than 8,300 patients with established ASCVD) and OCEAN(a)-Outcomes for olpasiran (NCT05581303, roughly 7,300 patients).

These are the first trials designed to test whether lowering Lp(a) actually reduces cardiovascular events, so the readouts will determine whether these agents reach practice. Neither is currently approved for general use.

Functional Medicine Approach

Since Lp(a) itself is hard to lower, the strategy is to reduce total cardiovascular risk:

• Reduce inflammation: Anti-inflammatory diet, omega-3s, curcumin, optimize vitamin D.
• Improve metabolic health: Control LDL, insulin resistance, blood pressure, and blood sugar.
• Use targeted supplements that may help lower Lp(a): L-carnitine, CoQ10, flax seed, xuezhikang (a red yeast rice extract), niacin.
• Lifestyle: Regular exercise, smoking cessation, stress management.

Conclusion

Lp(a) is a genetic, lifelong CVD risk factor that cannot be significantly altered by lifestyle or current medications. But with early identification and a comprehensive functional medicine plan, risk can be greatly reduced. By focusing on inflammation, metabolic health, and cardiovascular resilience, we can help patients with elevated Lp(a) live longer, healthier lives.

-Carey Kunz, ND, IFMCP

Director of Education at FMP Essentials

References

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About the FMP Essentials Mastermind

The FMP Essentials Mastermind is a clinical mentorship community for practicing physicians, NPs, and PAs applying functional medicine to real cases. Members join Dr. Yousef Elyaman, MD, IFMCP, for monthly live clinical deep dives, case-based learning, and a peer community of working clinicians. Learn more about the FMP Essentials Mastermind.