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 10–30% 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 will explain 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 2–3 times higher Lp(a) levels than those of European descent. Lp(a) is primarily genetic and follows an autosomal codominant inheritance pattern. In fact, >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 ~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: 30–50 mg/dL (75–125 nmol/L)
• High-risk: ≥50 mg/dL (≥125 nmol/L)

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) – statins may even increase it slightly.

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

Emerging Therapies

Several new therapies are being developed specifically to target Lp(a). Two of the most promising are pelacarsen and olpasiran, which are antisense oligonucleotide and small interfering RNA therapies, respectively. These agents work by targeting the LPA gene in the liver to significantly reduce the production of apolipoprotein(a). Clinical trials have shown these medications can reduce Lp(a) levels by 70–90%, offering a potentially groundbreaking option for high-risk patients [9]. While not yet approved for general use, they are progressing through late-stage clinical trials and may become an important tool in the near future.

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 to 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

1. Enas EA, Kannan S, Puthumana J, Chennikkara H, Bjurlin MA. Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction. Indian Heart J. 2019;71(2):99-112.
2. Tsimikas S. A test in context: Lipoprotein(a): Diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2018;71(22):2369-2386.
3. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: Current status. Eur Heart J. 2010;31(23):2844-2853.
4. Virani SS, Brautbar A, Davis MP, et al. Associations between lipoprotein(a) levels and cardiovascular outcomes in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) study.   2019;139(22):2641-2648.
5. Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518-2528.
6. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of myocardial infarction.   2009;301(22):2331-2339.
7. Wilson DP, Jacobson TA, Jones PH, et al. Use of lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol. 2019;13(5):655-662.
8. Marcovina SM, Albers JJ, Gabel B, et al. Effect of the number of apolipoprotein(a) kringle 4 repeats on immunochemical measurements of lipoprotein(a). Clin Chem. 2003;49(11):1785-1796.
9. O'Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk.   2019;139(12):1483-1492.
10. Banach M, Serban MC, Sahebkar A, et al. Effects of l-carnitine on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. 2016;26(5):392-399.
11. Kroon AA, Aengevaeren WR, van der Werf T. The influence of N-acetylcysteine on lipoprotein(a) levels in patients with chronic hyperlipidemia. J Intern Med. 1991;230(6):519-526.
12. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207.
13. Sahebkar A, Reiner Ž, Simental-Mendía LE, Ferretti G, Cicero AF. Effect of extended-release niacin on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized placebo-controlled trials. Metabolism. 2016 Nov;65(11):1664-1678. doi: 10.1016/j.metabol.2016.08.007. Epub 2016 Aug 31. PMID: 27733255.
14. Momtazi-Borojeni AA, Katsiki N, Pirro M, Banach M, Rasadi KA, Sahebkar A. Dietary natural products as emerging lipoprotein(a)-lowering agents. J Cell Physiol. 2019 Aug;234(8):12581-12594. doi: 10.1002/jcp.28134. Epub 2019 Jan 13. PMID: 30637725.
15. Sahebkar A, Simental-Mendía LE, Stefanutti C, Pirro M. Supplementation with coenzyme Q10 reduces plasma lipoprotein(a) concentrations but not other lipid indices: A systematic review and meta-analysis. Pharmacol Res. 2016 Mar;105:198-209. doi: 10.1016/j.phrs.2016.01.030. Epub 2016 Feb 2. PMID: 26836888.
16. Fogacci F, Di Micoli V, Sabouret P, Giovannini M, Cicero AFG. Lifestyle and Lipoprotein(a) Levels: Does a Specific Counseling Make Sense? J Clin Med. 2024 Jan 28;13(3):751. doi: 10.3390/jcm13030751. PMID: 38337445; PMCID: PMC10856708.