**Lipoprotein (a) **

What is Lipoprotein(a)?

Lipoprotein(a), pronounced “lipoprotein little a” and abbreviated as Lp(a), is a unique type of cholesterol particle in your blood that has emerged as one of the most important genetic risk factors for heart disease and stroke. Think of Lp(a) as LDL cholesterol’s dangerous cousin—it looks similar to LDL (“bad” cholesterol) but has an extra protein component attached to it called apolipoprotein(a), or apo(a) for short.[1] This extra protein component makes Lp(a) particularly harmful to your cardiovascular system. Unlike LDL cholesterol, which primarily delivers cholesterol to your arteries, Lp(a) has multiple ways of causing damage. It carries oxidized phospholipids—damaged fat molecules that trigger inflammation in your blood vessel walls. It can interfere with your body’s natural clot-dissolving system, making blood clots more likely to form and less likely to break down. And it promotes calcium deposits in both your arteries and heart valves, contributing to hardening of the arteries and aortic valve stenosis.[1][3] On an equal particle basis, Lp(a) is approximately 5 to 6 times more atherogenic (artery-damaging) than LDL particles, making it an exceptionally potent risk factor for cardiovascular disease.[4]

Why is Lipoprotein(a) Different from Other Cholesterol?

What makes Lp(a) fundamentally different from other cardiovascular risk factors is that your Lp(a) level is almost entirely determined by your genes—approximately 70-90% genetically determined—and remains relatively stable throughout your adult life.[1][5] This means that unlike LDL cholesterol, blood pressure, or blood sugar, your Lp(a) level is essentially set at birth and is not significantly influenced by diet, exercise, or most lifestyle factors.[6][1][7] Your Lp(a) level is inherited from both of your parents you get one LPA gene from each parent, and both contribute to your final Lp(a) level.[1] The most important genetic factor determining your Lp(a) level is the size of the apo(a) protein, which is controlled by the number of repeated protein segments called “kringle IV-2 domains.” People who inherit genes for smaller apo(a) proteins (with fewer kringle repeats) tend to have much higher Lp(a) levels—sometimes 5 times higher—than those with larger apo(a) proteins.[1][8] Because Lp(a) is genetically determined, it’s an excellent candidate for one-time screening. Once you know your level, you generally know your lifetime risk, and repeated testing is usually unnecessary unless you’re monitoring treatment.[10][3]

How is Lipoprotein(a) Measured?

Lp(a) is measured through a simple blood test that can be done at the same time as your regular cholesterol panel. Unlike traditional cholesterol testing, you do not need to fast before having your Lp(a) measured—your level remains stable whether you’ve eaten recently or not.[3] One challenge with Lp(a) testing is that results can be reported in two different units: milligrams per deciliter (mg/dL) or nanomoles per liter (nmol/L). Different laboratories use different units, which can be confusing.[3] The test should ideally use an assay that accounts for the fact that Lp(a) particles come in different sizes. Some older tests gave inaccurate results depending on your particular apo(a) size, but modern assays are designed to minimize this problem.[3]

Understanding Your Lipoprotein(a) Numbers

Because Lp(a) levels vary significantly across different ancestries and populations, there isn’t a single “normal” range that applies to everyone. However, most guidelines use similar thresholds for identifying elevated levels that increase cardiovascular risk:[11][3]

• Less than 30 mg/dL (less than 62 nmol/L): Lower risk—this is where most people fall
• 30-50 mg/dL (62-105 nmol/L): Moderately elevated—associated with increased cardiovascular risk
• Greater than 50 mg/dL (greater than 105 nmol/L): High risk—this threshold is used by most guidelines to identify people who need more aggressive cardiovascular risk management
• Greater than 180 mg/dL (greater than 430 nmol/L): Very high risk—comparable to having familial hypercholesterolemia (inherited high cholesterol) Approximately 20-25% of the global population has Lp(a) levels above 50 mg/dL, meaning elevated Lp(a) is quite common.[7] However, the distribution varies significantly by ancestry. People of African descent tend to have higher median Lp(a) levels than people of European or Asian descent, though the cardiovascular risk at any given Lp(a) level appears similar across ancestries.[1]

How Do we know Increased Lipoprotein(a) Increases Cardiovascular Risk

The evidence that elevated Lp(a) causes cardiovascular disease is now overwhelming and comes from multiple independent lines of research:[1][3] Genetic studies provide some of the strongest evidence. People born with genetic variants that cause very high Lp(a) levels develop heart disease much earlier in life. Conversely, people born with genetic variants that cause naturally lower Lp(a) levels have dramatically lower rates of heart disease throughout their lives, even when other risk factors are similar.[1][3] Large observational studies consistently show a continuous, dose-dependent relationship between Lp(a) levels and cardiovascular disease risk. The higher your Lp(a), the greater your risk, with no threshold below which lower isn’t better.[3][12] For every 50 nmol/L increase in Lp(a), cardiovascular risk increases by approximately 11%.[1] The relationship is log-linear, meaning that risk increases progressively as Lp(a) levels rise, with the highest risks occurring in people with the most elevated levels.[3][1] Elevated Lp(a) increases risk for multiple cardiovascular conditions, with the strongest associations seen for:[3]

• Myocardial infarction (heart attack): 1.7 to 3 times higher risk for people in the top 5% of Lp(a) levels
• Aortic valve stenosis: 1.7 to 3 times higher risk
• Ischemic stroke: 1.2 to 1.6 times higher risk
• Cardiovascular and all-cause mortality: 1.2 to 1.6 times higher risk Elevated Lp(a) increases risk in both people without known heart disease (primary prevention) and in people who already have cardiovascular disease (secondary prevention). In fact, high Lp(a) is associated with recurrent cardiovascular events even in people receiving optimal medical therapy.[3][12] Frequently asked questions

Why is Lipoprotein(a) Testing Important?

Given that Lp(a) is a common, genetically determined, causal risk factor for cardiovascular disease, testing for it provides several important benefits: 1. It identifies hidden cardiovascular risk. Many people with elevated Lp(a) have no other obvious risk factors. Knowing your Lp(a) level helps you and your doctor understand your true cardiovascular risk and make informed decisions about prevention strategies.[1][3] 2. It explains cardiovascular disease that seems unexplained. If you or a family member developed heart disease at a young age despite having normal cholesterol and blood pressure, elevated Lp(a) may be the explanation.[11][15] 3. It guides treatment intensity. People with elevated Lp(a) benefit from more aggressive management of other modifiable risk factors, particularly LDL cholesterol.[3][1] 4. It enables family screening. Because Lp(a) is inherited, if you have elevated Lp(a), there’s a 50% chance each of your children and siblings also has elevated levels. Testing family members can identify others at increased risk.[1] 5. It’s a one-time test. Because Lp(a) levels are genetically determined and remain stable throughout adult life, you generally only need to be tested once (with the exception of women, who may experience a modest increase after menopause and should consider retesting about 5 years after menopause).[3]

Who Should Be Tested for Lipoprotein(a)?

Guidelines from major cardiovascular organizations around the world now recommend Lp(a) testing for everyone[11][1][3] The European Society of Cardiology/European Atherosclerosis Society and the Canadian Cardiovascular Society recommend that all adults be tested for Lp(a) at least once in their lifetime, ideally as part of their first lipid screening.[11][3] Given that Lp(a) is common (affecting 20-25% of the population), genetically determined, causal for cardiovascular disease, and requires only a one-time test, many experts believe universal screening of all adults is justified and will become standard practice as Lp(a)-lowering therapies become available.[1][3]

What Can You Do About Elevated Lipoprotein(a)?

Lipoprotein(a) is largely genetically determined, so diet, exercise, weight loss, and smoking cessation do not meaningfully lower Lp(a) itself. That said, these lifestyle changes remain very important because they reduce many other cardiovascular risk factors that interact with Lp(a). In other words, you may not be able to change your Lp(a) level, but you can still substantially lower your overall heart risk.[6][1][3][7] [16]

References

1. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Arteriosclerosis, Thrombosis, and Vascular Biology. 2022;42(1):e48-e60. doi:10.1161/ATV.0000000000000147.
2. Lipoprotein(a) and its Significance in Cardiovascular Disease: A Review. Duarte Lau F, Giugliano RP. JAMA Cardiology. 2022;7(7):760-769. doi:10.1001/jamacardio.2022.0987.
3. Lipoprotein(a) and Cardiovascular Disease. Nordestgaard BG, Langsted A. Lancet (London, England). 2024;404(10459):1255-1264. doi:10.1016/S0140-6736(24)01308-4.
4. Lipoprotein(a) as a Pharmacological Target: Premises, Promises, and Prospects. Greco A, Finocchiaro S, Spagnolo M, et al. Circulation. 2025;151(6):400-415. doi:10.1161/CIRCULATIONAHA.124.069210.
5. Repeat Measures of Lipoprotein(a) Molar Concentration and Cardiovascular Risk. Trinder M, Paruchuri K, Haidermota S, et al. Journal of the American College of Cardiology. 2022;79(7):617-628. doi:10.1016/j.jacc.2021.11.055.
6. Non-Genetic Influences on Lipoprotein(a) Concentrations. Enkhmaa B, Berglund L. Atherosclerosis. 2022;349:53-62. doi:10.1016/j.atherosclerosis.2022.04.006.
7. Role of Lipoprotein(a) in Atherosclerotic Cardiovascular Disease: A Review of Current and Emerging Therapies. Alhomoud IS, Talasaz A, Mehta A, et al. Pharmacotherapy. 2023;43(10):1051-1063. doi:10.1002/phar.2851.
8. Lipoprotein(a) Beyond the Kringle IV Repeat Polymorphism: The Complexity of Genetic Variation in the LPA Gene. Coassin S, Kronenberg F. Atherosclerosis. 2022;349:17-35. doi:10.1016/j.atherosclerosis.2022.04.003.
9. Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease. Clarke R, Peden JF, Hopewell JC, et al. The New England Journal of Medicine. 2009;361(26):2518-28. doi:10.1056/NEJMoa0902604.
10. Genetics and Pathophysiological Mechanisms of Lipoprotein(a)-Associated Cardiovascular Risk. Volgman AS, Koschinsky ML, Mehta A, Rosenson RS. Journal of the American Heart Association. 2024;13(12):e033654. doi:10.1161/JAHA.123.033654.
11. Ancestry, Lipoprotein(a), and Cardiovascular Risk Thresholds: JACC Review Topic of the Week. Tsimikas S, Marcovina SM. Journal of the American College of Cardiology. 2022;80(9):934-946. doi:10.1016/j.jacc.2022.06.019.
12. Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort. Wong ND, Fan W, Hu X, et al. Journal of the American College of Cardiology. 2024;83(16):1511-1525. doi:10.1016/j.jacc.2024.02.031.
13. Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease. Trinder M, Uddin MM, Finneran P, Aragam KG, Natarajan P. JAMA Cardiology. 2021;6(3):287-295. doi:10.1001/jamacardio.2020.5398.
14. Lipoprotein(a), C-Reactive Protein, and Cardiovascular Risk in Primary and Secondary Prevention Populations. Small AM, Pournamdari A, Melloni GEM, et al. JAMA Cardiology. 2024;9(4):385-391. doi:10.1001/jamacardio.2023.5605.
15. NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis. Tsimikas S, Fazio S, Ferdinand KC, et al. Journal of the American College of Cardiology. 2018;71(2):177-192. doi:10.1016/j.jacc.2017.11.014.
16. Lipoprotein(a) and Effects of Diet: Time for Reassessment. Enkhmaa B, Berglund L. Nutrients. 2025;17(10):1714. doi:10.3390/nu17101714.
17. Clinical Trial Design for Lipoprotein(a)-Lowering Therapies: JACC Focus Seminar 2/3. Malick WA, Goonewardena SN, Koenig W, Rosenson RS. Journal of the American College of Cardiology. 2023;81(16):1633-1645. doi:10.1016/j.jacc.2023.02.033.